Dr. Adriana Rossi, a myeloma expert and researcher, discusses how CAR T-cell therapy has revolutionized care, the process for undergoing this therapy, common side effects of this treatment, and advice for patients considering this option. Dr. Rossi also shares updates in CAR T-cell therapy research and explains what she’s excited about in myeloma care.
Dr. Adriana Rossi is Co-director of the CAR T and stem cell transplant program at the Center for Excellence for Multiple Myeloma at Mount Sinai Health System in New York City. Learn more about Dr. Rossi.
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Transcript:
Katherine Banwell:
Hello, and welcome. I am your host, Katherine Banwell. Today’s program is part of our Thrive series, where we will discuss what to expect and how to manage side effects of CAR T-cell therapy.
Before we get into the discussion, please remember that this program is not a substitute for seeking medical advice. Please refer to your healthcare team about what might be best for you.
Well, let’s meet our guest today. Joining us is Dr. Adriana Rossi. Dr. Rossi, welcome. Would you please introduce yourself?
Dr. Adriana Rossi:
Thank you so much. I am one of the codirectors of the CAR T program at Mount Sinai in New York City and thrilled to be with you today.
Katherine Banwell:
Thank you. Since we’ll be discussing the ins and outs of CAR T-cell therapy, I thought we could start with your perspective as a researcher in the field. How has this therapy revolutionized myeloma care?
Dr. Adriana Rossi:
It absolutely has. And I would say in time we’ve had – this is now our fourth revolution. Stem cell transplants was the first time we actually achieved what we call a complete remission in at least a few patients, making myeloma disappear.
Then, we had the second revolution with the novel agents. Now, we had drug therapies that were giving us these complete remission still at about a 30 percent rate. And then, the monoclonal antibodies were the most recent revolution. And currently, we are in what we call the T-cell redirection.
It really has been driven by CAR T-cell therapies and something we call bispecific antibodies, which also use your patient’s T cells to kill the myeloma. We are now seeing absolutely unprecedented response rates, meaning almost everybody is responding. Also, depth of response, which we have really learned over time is a way to translate into long remissions. So, every long, very significant remissions. And the early data in patients who have had many prior lines.
Katherine Banwell:
So, it is very encouraging news.
Dr. Adriana Rossi:
It is very encouraging.
Katherine Banwell:
Let’s start with an overview of CAR T-cell therapy. Could you explain how the treatment works?
Dr. Adriana Rossi:
Absolutely. So, CAR T specifically is speaking to T cells, which are a normal part of the immune system that have been engineered and modified. So, normal part of the immune system T cells have a lot of checks and balances and are constantly looking for cells that are supposed to be killed. For example, something that has a virus in it.
When we engineer the CAR T-cells, we modify, one, the target so they are now trained to find the specific target on a tumor cell. And we remove all these checks and balances. So, once that T-cell finds its target, it can kill it without all of the side effects. The way normal T cells communicate with other members of the immune system are something called cytokines. So, we will touch on that a little later, I think, but we also, again, interfere with that communication by engineering the cells.
Katherine Banwell:
Which patient type qualifies for CAR T?
Dr. Adriana Rossi:
In 2023, we currently have two approved commercial CAR T products and we do have a number of them in clinical trials. The two that are commercially approved specifically are targeted for patients who are in their fourth line of therapy, so the myeloma has learned to come back that four times.
They’ve been exposed to all of the regular drugs, which by four lines most patients will have been at least once. We look for patients whose kidney function is at a safe level to tolerate the therapy. And other than that, it’s really having caregiver support and overall ability to come to a center that specializes in this.
Katherine Banwell:
What’s the process for accessing the CAR T?
Dr. Adriana Rossi:
The first important part is remembering they exist and having the referring physician remember to send patients our way. Once patients come to our center, they will meet with coordinators, both the clinic coordinators to make sure we have all of the testing, to make sure the heart is healthy enough, the lungs are healthy enough. There’s no infections brewing.
Financial coordinators to take care of all of the organizing. If patients are coming from further than 30 minutes, setting them up for a place to stay in the city, transportation aid, all of those things. Once we decide to go ahead and have our collection date set, that sort of starts the actual process. Since most of our patients have had stem cell transplants before, there is that point of comparison. I think one of the most important things to remember is CAR T is not stem cells.
So, while they’re both the cellular therapies, the patient experience is vastly, vastly different. It starts with a collection, where in stem cells you need several days of injections and maybe several days of collection. T-cell collection is a one-day event. We get what we get and then we are going to manufacture them and we can grow them in a Petri dish. There is no minimum and there is no instigating injections to get them going.
Once they’re collected, the cells are then sent for manufacturing, which may take from four to eight weeks. During that time, patients usually receive what we call a bridging therapy, which is some kind of therapy to keep the myeloma at bay. Not to get rid of it but to keep it under control so that once the cells are ready the patient is also ready. Going into CAR T with growing myeloma can increase the side effects.
Katherine Banwell:
Go ahead.
Dr. Adriana Rossi:
I will give you just the final bit. Once the cells are ready, then we plan to give chemotherapy to get the patient’s T cells to not put up a fight. That’s called lymphodepletion. We infuse the cells and they’re now with us for two weeks in the hospital and usually two weeks after.
Katherine Banwell:
Okay. So, I was going to ask how long patients are in the hospital for the procedure. So, that explains that. So, it is about two weeks. What signifies that a patient is ready to be released and go home?
Dr. Adriana Rossi:
The reason patients are in the hospital is a very classic expected toxicity experience. So, they’re in the hospital for us to observe, watch. If it happens, which about 80 percent of the time there will be some toxicity for us to address – one that toxicity has resolved, they’re then okay to go home.
Katherine Banwell:
Okay. That is great advice. Thank you. Of course, we know that CAR T-cell therapy comes with some potential side effects. Let’s talk about some of those side effects and how they’re managed. You mentioned cytokine release syndrome earlier. Let’s start with that. What is it, exactly?
Dr. Adriana Rossi:
Yes. As I mentioned, cytokines are molecules that the cells of the immune system use to communicate with each other. With this therapy, we are asking the T cells that have been infused to expand, meaning make multiple copies of themselves, and sweep through the body looking for myeloma and basically picking a fight with them.
So, CRS is what happens when the T cells are too good at their job and they overachieve and then picking a little fight kind of make a big ruckus. The result is what we call inflammation, which the patient will experience usually as a fever.
But if it does not go – if it continues to go unchecked, that fever can be accompanied by low blood pressure because of these inflammatory markers, difficulty breathing or low oxygen levels. And all of these things are now vastly prevented. CRS is usually treated very quickly and doesn’t get to these higher grades, more complicated fields.
Katherine Banwell:
How is CRS managed?
Dr. Adriana Rossi:
We have a couple of very good antidotes. CRS by itself is not just a fever. Certainly, a fever in any patient who is undergoing these kinds of therapies, we will try to rule out any infections. But there are markers in the blood that we can follow. When the blood markers and the fever occur at the same time, we know that cytokines are driving that effect. If it seems to be driven by something we call IL-6, we use tocilizumab (Actemra). If it seems to be driven by IL-1, we use anakinra (Kineret). These are all drugs that are themselves monoclonal antibodies which then will shut down that overreaction and cool things down.
Katherine Banwell:
Okay. Another possible side effect is neurotoxicity. Would you define that term for us?
Dr. Adriana Rossi:
Yes. That one is harder to define because neurotoxicity in itself is very broad. We usually think of something called ICANS, which is the neurotoxicity associated with the effector cells. That specific neurotoxicity tends to happen in conjunction with CRS.
And while CRS probably occurs in about 85 percent of patients, the ICANS is usually in the order of 5 percent. So, much, much more rare. And the antidote for that, which most patients know, love, and hate, is steroids.
Katherine Banwell:
Ah, yes.
Dr. Adriana Rossi:
I should mention there are other parts of neurotoxicity which I think the most concerning is something that has been known as Parkinsonian symptoms. It’s really just movement disorder. These are exceedingly rare and so we haven’t had a chance to learn very much because there are so few patients who have had this complication. We have learned from the first six patients who had this how to avoid it. And so, I think it’s now even more rare and it really goes into patient selection, to making sure, as I mentioned, that the myeloma isn’t growing very much.
We monitor to see if the T cells grow too fast, if the CRS is of a high level. These are all predictors of delayed neurotoxicity.
Katherine Banwell:
What are the signs of neurotoxicity in a patient?
Dr. Adriana Rossi:
Very specifically, for the ICANS, we have tool called the ICE tool, which is a series of questions to test memory and attention and ability to write and understand and speak. So, most commonly, it would be an inability to speak properly or, if someone is writing a sentence, it’s really a very classic finding. It is no longer spread across the page.
These are not subtle findings. Part of, again, being in the hospital is to allow us to have this tool twice a day and look for these signs very early on, interfere with their development by giving the patients steroids – usually for a day or two – and resolving it.
Katherine Banwell:
So, that’s how neurotoxicity is managed, then.
Dr. Adriana Rossi:
Yes.
Katherine Banwell:
And is there a potential for long-term issues associated with neurotoxicity?
Dr. Adriana Rossi:
Certainly, there is always the potential. But the vast majority – again, the ICANS tend to be self-limited while the patient’s in the hospital, and that is why we’re watching during that window. The delayed neurotoxicities, in addition to these very rare movement disorders, we do see some cranial nerve palsies. The seventh cranial nerve, usually recognized as Bell’s palsy, has happened a few times. We really don’t understand the mechanism of what is driving it. It’s inflammation but why there, why that way. So, we tend to use acyclovir, which is the classic treatment for Bell’s palsy and steroids.
Katherine Banwell:
Dr. Rossi, a suppressed immune system is something that a patient undergoing CAR T-cell therapy should consider. What does it mean and what precautions should patients take?
Dr. Adriana Rossi:
That is such a good question and it is specifically true for patients who are receiving therapies that target BCMA, which both commercial CAR Ts at the moment target.
Because it is such an effective therapy at bringing down cells that express BCMA, your immune cells that make antibodies, one of the side effects is the immunoglobulins, which are the antibodies, are all very, very low. So, that is one level of immunosuppression.
The other is the chemotherapy that we use to quiet the T cells can also lower all the blood counts. So, red blood cells and platelets may be low as well and those are not involved with immunity and can be transfused. So, that is a supportive mechanism. For the immune therapies, we usually use IVIG, which is intravenous immunoglobulins to support the patient until they’re able to make their own.
We also protect them from viral infections with acyclovir or valacyclovir. Protect them from something called PJP pneumonia, which is a virus that specifically appears when you’re very immunosuppressed. Should their neutrophil count be low, that is another type of white blood cell – make sure they’re protected with antibiotics.
Katherine Banwell:
Is there a typical timeframe for the immune system function to return?
Dr. Adriana Rossi:
I would say a year is a good time but it’s a very unpredictable wave. So again, unlike stem cell transplant where you have a clear time where the cells are low, they recover, they stay recovered, we have noticed for some patients, they may have low blood counts just during the first month and then be recovered. Some will have no problems in the first month and it’s in the weeks to follow that suddenly either the reds, or the platelets, or the white count may need support.
And in very rare instances, out to a year, they’re still needing support, sometimes say a growth factor injection once a week.
Katherine Banwell:
So, how is it monitored over time?
Dr. Adriana Rossi:
We monitor all those different levels of the immune system. So, we check on the CBC, which is the very common blood counts. We also look at what is called a lymph panel to look at the different types of T cells and make sure that they are recovering. Those usually take about three to six months to recover. The white count, again usually by Day 30, but there are some cases of delayed recovery. And the immunoglobulins, which is the antibody level, we also monitor monthly.
Katherine Banwell:
What other side effects should patients who are considering CAR T-cell therapy be aware of?
Dr. Adriana Rossi:
Really, those are the big three. I would say others are very rare but the low blood counts is the one that lasts beyond the time in the hospital. And the rare neurotoxicities that are delayed.
Katherine Banwell:
When should patients mention any issues they’re experiencing to their healthcare team?
Dr. Adriana Rossi:
Always. That is a very, very, short answer. Please don’t ever think you are bothering the doctor. I hear that a lot. “Oh, I didn’t want to bother you.” It is never a bother. This is why we are here. So, anything that is happening that is out of the ordinary, please let your healthcare provider know. If it is not something that needs our attention or we don’t need to worry about, we will tell you.
Katherine Banwell:
Better safe than sorry.
Dr. Adriana Rossi:
Always.
Katherine Banwell:
And how does a care partner factor into the process? It seems having a good support system is essential.
Dr. Adriana Rossi:
It absolutely is. I think the entire journey of myeloma really is what I would consider a team sport. It is not something we go through alone. And the more members of the team you have the better. So, as your medical team, we always value the caregivers. For CAR T specifically, since there is this concern for infections and neurotoxicity, caregivers are really essential. They should be well informed, know what to look for, and be the ones to reach out to us if anything is concerning. Again, any symptoms out of the ordinary, any fever, and really be a part of communicating with the medical team.
Katherine Banwell:
Is there a period where patients are considered out of the woods from CAR T side effects?
Dr. Adriana Rossi:
Hard to say. Again, I like to emphasize that most patients by Day 30 or 60 are back to work, are feeling themselves, are recovered. Another contrast to stem cell transplants. It’s a much faster recovery. I have patients who within 30 days are eager to go back to work and don’t know what I was talking about or why I insist on seeing them so much.
But some patients, again, out to a year, may still be requiring visits for support in either the IVIG for the immunoglobins, growth factor support for their counts. So, there are outliers at both extremes. We follow the model of 100 days for recovery.
Katherine Banwell:
Do some patient types do better than others?
Dr. Adriana Rossi:
Well, always yes. And we are still endeavoring to figure out who they are and why that is. There are things that we don’t know, can’t predict. But things that we do recognize are again bringing patients whose myeloma is under good control.
So, instead of having a lot of disease or disease that is in a growth phase, we try to use the bridging therapy to optimize the patient, not only to improve the response, but also minimize the toxicities.
Katherine Banwell:
Does age have an impact at all?
Dr. Adriana Rossi:
Not as much. We actually have just finished an 88-year-old patient whose hospital course was remarkably unremarkable, as we would like. I think another difference from stem cells, it is not as rigorous. While each patient, I think, should be part of that decision and that conversation, reviewing what is now a growing number of options and see if it’s right for them as an individual. So, age is a consideration, but frailty will always be the more important.
Katherine Banwell:
Dr. Rossi, we discussed the process of accessing CAR T-cell therapy, which can be a big undertaking. How do you counsel patients who are considering this treatment option?
Dr. Adriana Rossi:
Mostly, I want to make sure that they are well-educated and understand as much as we do and as much as we can convey. I am fortunate to be part of a big multidisciplinary team so there is social workers, clinical coordinators, other specialists, dentists, cardiologists, to give all of the perspectives. I like to make sure that they know what it is and also that they know what it isn’t. So, it is not a stem cell transplant and it is not another line of therapy that you just sign up for and go into blindly.
So, making sure they’ve had all of their questions answered, and it’s not something they read on the Internet. They have spoken with one of the CAR T physicians, understand all of the steps of the process, and have questions to their very individual needs addressed.
Katherine Banwell:
If a patient is interested in possibly doing CAR T-cell therapy, what questions should they ask their healthcare team?
Dr. Adriana Rossi:
I think again making it personal to them. Does the team think they are a good candidate? Is this the right time? Because they may be a good candidate but not even need it at the moment. Or, again, there are things that we could do between now and the cells to optimize the success both in efficacy and toxicity.
Understanding what side effects are expected for that individual because, again, we can usually judge these will be more likely or less likely. And then, do I have a plan in place to find the right center and continue the care and the monitoring near home after that?
Katherine Banwell:
What are the alternatives if a patient decides CAR T is not right for them?
Dr. Adriana Rossi:
I would say as part of this newest revolution and fairly comparable in novelty and method of action would be the bispecific antibodies. So, these are molecules.
They are not cells. And they activate the patient’s own T cells and bring the T cells to the myeloma, causing very similar side effect profile and very similar effectiveness. The rates are a little bit lower but they are administered as mostly a subcutaneous injection that has to be dosed weekly or every other week. The contrast is it’s a continuous therapy, but it does allow us to adjust as we go, which the cellular therapy doesn’t.
Katherine Banwell:
While there are approved CAR T-cell therapies for myeloma currently, there are also many others that are in clinical trials. Would you talk about some of the ongoing research in this area?
Dr. Adriana Rossi:
Absolutely. Again, while we celebrate the tremendous changes that these two CAR Ts have made to the field, they are both autologous, meaning we use the patient’s own T cells for manufacturing. They both target BCMA. And they are both what we call second generation T cells. So, other areas are to change the target. So, instead of just targeting BCMA, there are studies specifically targeting GPRC5D, which are coming down fairly soon. Rather than using the patient’s own T cells there are a number of products that use a healthy donor’s T cells, which are available immediately.
So, we don’t need to go through the bridging therapy, and we don’t have to wait for the cells to be ready. And lastly, there are different manufacturing processes. As I mentioned, the ones we currently have may take up to eight weeks for manufacturing. There are some studies now where cells are basically manufactured, engineered, in 48 hours –
Katherine Banwell:
Oh, wow.
Dr. Adriana Rossi:
– and are ready to be infused so that they actually grow in the patient rather than in a Petri dish. So, lots of areas of exploration and I look forward to, in five years, being able to look back and see again how the field has changed.
Katherine Banwell:
And I’m sure it will, by the sounds of it. Are there any trials introducing CAR T-cell therapy as an earlier line of myeloma treatment?
Dr. Adriana Rossi:
There are. So, both the products that are now commercially available for the fourth line are being studied in earlier and earlier lines. We actually just this year got results of the CARTITUDE-4 study, which was in one to three prior lines, and expect that that will lead to an earlier approval in the very near future.
And we have a number of studies, again, with both products looking at patients who have either high risk disease or don’t respond as well as we would like to their frontline therapy, and actually being used as part of that first line.
Katherine Banwell:
Dr. Rossi, what advice do you have for patients who may be hesitant to participate in a clinical trial?
Dr. Adriana Rossi:
Education. More than anything, understand what they are. Clinical trials come in all shapes and sizes. We have these exciting molecules that have to go into a first human at some point but we also have tried and true therapies that we know – for example, the CAR T – that is approved in these later lines. That same product is being now offered earlier. So, that has to be within a clinical trial because it’s not the approved indication.
But it is a product that we know to be safe. We know that it works in advanced disease and are actually expecting that it will work even better in earlier lines. So, clinical trials is a very broad term. Understanding what the patient may be eligible for – meaning, what the study’s looking for – and then comparing that to what the patient is looking for. So, sometimes it’s even modes of therapy. So, if you’re specifically looking for an oral agent, there may be studies that don’t require injections or that many visits. So, really looking widely, speaking to your healthcare physician, and understanding what the options are.
Katherine Banwell:
And if a patient is interested in possibly participating in a clinical trial, what sorts of questions should they ask?
Dr. Adriana Rossi:
Very, very good question. First, understanding what clinical trial. Each center will have their own combination. Some studies are available in multiple locations. Some studies are very institution specific. So, meeting with the research team and understanding what are the required testings, what is the required treatments, and what is the required follow-up, I think, is the first part.
Clinical trials, in order for them to give us the power to generalize and learn lessons are very strict in trying to keep to the schedule just as specified and everything is much more contained. So, making sure that they again understand what they’re signing up for and what they’ll get out of it.
Katherine Banwell:
What other myeloma research are you excited about?
Dr. Adriana Rossi:
Well, my focus is in CAR T and so I think, with bias, that is the most exciting part. But I did mention bispecifics. One of the things we need to concede is CAR T really requires you be at a cellular therapy center.
Whereas, with the bispecifics, while for now experience is still building, the idea is that this is something that could be administered in any practice across the nation. So, being able to reach more patients and those also with different targets, different schedules, different combinations, was another very interesting field as well.
Katherine Banwell:
As we close out this conversation, Dr. Rossi, I would like to get your take on the future of myeloma. What makes you hopeful?
Dr. Adriana Rossi:
Just looking back, I think. Again, in the 20 years that I’ve been fortunate enough to participate and see the changes, we have gone through, as I mentioned, three of the four revolutions in the field. And the speed with which each step forward then begets three or four more. As I mentioned, in five years I think we’ll look back and say, “Oh, how quaint, what we were doing in 2023.” So, the speed and the number of wins we’re getting and how quickly that’s translating into direct patient experience is really incredible.
Katherine Banwell:
Yeah. It seems like there’s a lot of progress and hope in the field.
Dr. Adriana Rossi:
There absolutely is.
Katherine Banwell:
Well, Dr. Rossi, thank you so much for taking the time to join us today.
Dr. Adriana Rossi:
Absolutely. It’s been my pleasure.
Katherine Banwell:
And thank you to all of our collaborators. To learn more about myeloma and to access tools to help you become a proactive patient, visit powerfulpatients.org. I’m Katherine Banwell. Thanks for being with us today.
Thrive | What You Should Know About MPN Symptoms & Treatment Side Effects
/in MPN Newly Diagnosed, MPN Programs, MPN Treatments and Clinical Trials, MPN Videos ND, MPN Videos TC, Myeloproliferative Neoplasms, Thrive MPN, Thrive MPN Managing /by Kara RayburnThrive | What You Should Know About MPN Symptoms & Treatment Side Effects from Patient Empowerment Network on Vimeo.
How are MPN symptoms and treatment side effect managed? In this animated explainer video, an MPN specialist and myelofibrosis patient discuss the importance of clear communication with your healthcare team, the process for assessing common issues, and advice for advocating for yourself.
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Transcript:
Brian:
Hi, I’m Brian. Nice to meet you! I’ve been living with a condition called myelofibrosis for many years. While there have certainly been ups and downs, I’ve been able to navigate care for my condition and to live a full life.
So how have I been able to do that? First and foremost, I have a great relationship with my care team, whom I communicate with regularly. Meet, Dr. Liu – my doctor.
Dr. Liu:
Hi! I’m Dr. Liu, and I’m a hematologist and a specialist in myeloproliferative neoplasms or MPNs. The three types of MPNs are essential thrombocythemia, or ET, polycythemia vera or PV, and myelofibrosis, or MF. This group of blood cancers is characterized by the bone marrow overproducing a certain type of cell.
Maintaining a good relationship with your healthcare team, coupled with finding a treatment approach that works for you, can help you live a full life and to thrive with an MPN.
Brian:
Exactly, Dr. Liu. Over the years, I’ve experienced periodic issues with my condition. I’ve had symptoms and treatment side effects that have been bothersome and interfered with my life. But, communication with my team has been essential to feeling well.
Dr. Liu:
That’s right, Brian. When symptoms or treatment side effects are bothering you, it’s important to let your healthcare provide know how you are feeling.
Brian:
For example, recently I felt tired beyond general sleepiness. And when I shared this with Dr. Liu, we discussed potential causes of the fatigue, and we talked in-depth about my options to manage it, including changing therapy and some simple changes to my diet and lifestyle.1 Over time, my energy levels improved, but having the open dialogue with Dr. Liu was essential to tackling this symptom head-on.
Dr. Liu:
That’s a great example. When I first hear from a patient that they are having an issue, we go through several steps to find a solution.2
We start by ensuring that the disease is well-controlled, so we check blood counts. Next, we try to determine if it is a symptom of the MPN or a side effect of the treatment. Once we’ve done those steps, we come up with potential solutions which may include, but are not limited to:
Other considerations are dependent upon the specific symptoms and side effects but may include:
Brian:
That’s good to know, Dr. Liu. Something you brought up with me, which I feel is important to mention, is mental health. Often, emotional symptoms can take a toll on the body, causing fatigue or other issues.
Dr. Liu:
Great point, Brian. Seeking care for your mental health is crucial, particularly if you are in active treatment.
Brian:
Of course, we know that the symptoms and treatment side effects for MPNs can vary widely, so what advice do you have for patients who may be afraid to speak up?
Dr. Liu:
The most important thing to remember is that we have options to help you, no matter what you are going through. It’s your body and if you don’t let your provider know what you’re going through, they can’t help you.
Brian:
So true. It’s also a good idea to bring a care partner along to appointments, sometimes a spouse or friend can you help you communicate what’s going on.
Dr. Liu:
That’s great advice, Brian. Bringing someone along to take notes is a great idea. Also, be sure to write down any questions or concerns you have in advance to make the most of your appointment.
Brian:
OK, Dr. Liu, let’s recap your advice for MPN symptom management:
Dr. Liu:
Good idea! First, remember that everyone’s MPN is different, so managing symptoms and side effects can be tricky. Communicating with your healthcare team is critical to your overall care – report any and all concerns to your team immediately.
And, do your part. Make sure you see your primary care physician regularly and do your best to maintain a healthy lifestyle.
Brian
And, most importantly, remember you are at the center of your care. Never hesitate to share your opinion and to advocate for yourself.
To learn more, visit powerfulpatients.org/MPN to access a library of tools. Thanks for joining us!
PODCAST: What Non-Small Cell Lung Cancer Treatment is Right for You?
/in Empowered! Podcast, LC Newly Diagnosed, LC Podcasts ND, LC Podcasts TC, LC Treatments and Clinical Trials, Lung Cancer, PEN Blog /by Kara RayburnWhat’s the best approach for YOUR lung cancer? Dr. Isabel Preeshagul discusses the importance of engaging in your lung cancer care decisions, shares advice for working with your team to determine a treatment approach, and reviews factors that affect therapy options. Dr. Preeshagul also provides an update on the latest research and clinical trials.
Dr. Isabel Preeshagul is a thoracic medical oncologist at Memorial Sloan Kettering Cancer Center. Learn more about Dr. Preeshagul.
Download Program Resource Guide
See More From INSIST! Lung Cancer
Transcript:
Katherine Banwell:
Hello and welcome. I’m Katherine Banwell, your host for today’s program. Today, we’ll discuss the latest advances in non-small cell lung cancer care as part of our Insist series, which encourages patients to play an active role and insist on better care. Before we get into the discussion, please remember that this program is not a substitute for seeking medical advice. Please refer to your healthcare team about what might be best for you. Well, let’s meet our guest today. Joining me is Dr. Isabel Preeshagul. Dr. Preeshagul, it’s so good to have you with us. Thank you. Would you introduce yourself?
Dr. Isabel Preeshagul:
Yes. Thank you so much for having me and for the very kind introduction. My name’s Isabel Preeshagul. I am a Thoracic Medical Oncologist at Memorial Sloan Kettering Cancer Center, and it is a huge honor to be here with you today.
Katherine Banwell:
Well, we’re so glad to have you with us. I’d like to start with a question pertaining to our series title, Insist. Why is it essential for patients to collaborate with their providers on care treatment decisions?
Dr. Isabel Preeshagul:
So, collaborating is so important, right? I always tell my patients this is not a dictatorship, right? This is a collaborative effort where I’m here to guide you, but you are the captain of the ship.
You are the one that needs to make all of the decisions, and I’m here to make sure that the ship goes in a smooth direction, so making sure we have open lines of communication that the patients and their caregivers feel comfortable talking to me and my team and also vice versa and that we trust each other. It’s so important because we are going for a marathon, right? We’re not going for a sprint. This is a long-term relationship, whether we’re treating for cure or we’re treating you with palliative intent and it’s treatable but not curable. We’re going to be following with each other for a long time.
Katherine Banwell:
A lung cancer healthcare team, of course, consists of a number of different providers. Would you tell us about the various members on a team?
Dr. Isabel Preeshagul:
Sure. So, there is – there are the people that do the scheduling, that make sure that the CAT scan is scheduled, that the MRI is done, your chemo gets scheduled, all of that. The schedulers are super important and an integral part of our team.
And then we also have our office coordinators that answers the phone calls and passes along the messages and assists with scheduling and sort of sets expectations and is the face of the practice. Then you have an office practice nurse or an oncology practice nurse who is the doctor’s right hand, making sure that the patients get proper chemotherapy teaches, making sure that they understand about possible side effects, risks versus benefits, making sure medications are up to date, assessing symptoms.
They are sort of the front line when it comes to any patient call they’re triaging, and they’re escalating or deescalating. That would be the office practice nurse. And then you have an advanced care practitioner, an APP. You either have a nurse practitioner or a PA that’s working with you that’s sometimes seeing patients independently, sometimes putting chemotherapy orders, you know, really serving as almost as another doctor.
If for some reason there is something that the doctor’s not available to do, the doctor needs in a pinch, or my patients that are almost at long-term follow-up that are doing great that are just kind of coasting, I will share with my NP and make sure that they know her just as well as they know me. And sometimes there’s a fellow or there’s a resident or there’s a med student that’s part of the team as well because see one, do one, teach one. It’s really important to teach those that are coming after you and serve as mentors and really include them in part of the team and part of the decision-making. And then you have the doctor that just kind of oversees everything.
Katherine Banwell:
Of course. How would you define treatment goals for people with lung cancer?
Dr. Isabel Preeshagul:
So, the goal of treatment, I think, is really contingent upon someone’s stage, but it’s also contingent upon what’s important to the patient, right? So, we have patients that are stage I all the way to stage IIIC that we treat with intention to cure.
And patients that have stage IV disease, it’s treatable but not curable. So, I am very transparent with that as long as I have the information to have that discussion. With that being said, there are some patients with stage IIIdisease or stage I disease that don’t really want treatment and want to focus on quality of life. And that’s okay too. And in which case, you know, at some point, their cancer will likely progress. How quickly or when that will happen, we don’t know. Could they pass from something else? It’s possible. But you really need to talk about what’s important to the patient, because it’s not always cut and dry.
Katherine Banwell:
As you mentioned, Dr. Preeshagul, there are several different support members on a team. What would you say to patients or even care partners who can sometimes feel like they’re bothering their healthcare team with their questions and comments?
Dr. Isabel Preeshagul:
So, we do get that concern a lot. And I always say, “I’m here for you 24/7. And, if it’s not me, it’s someone that’s just as qualified to answer your questions no matter what.”
“And I would rather get a phone call at 3:00 a.m. than get a phone call at 9:00 a.m., and you need to go to the hospital right now or God forbid something happened. I get a phone call from someone in the ICU that you went overnight and terrible things happened. So, I want the phone calls to come through to keep you out of the hospital and keep you from going south. So, call me.” And I never try to – I don’t try to outline contingency plans or criteria of what would warrant a call, because then you end up getting in trouble.
I always just tell my patient, “Think about how you’re feeling now in front of me. If you’re feeling any different than how you feel at this very moment, call me.”
Katherine Banwell:
Good advice. I’d like to turn to the clinical side of non-small cell lung cancer. What tests help you identify the type and stage of lung cancer?
Dr. Isabel Preeshagul:
Obviously, you need a CAT scan. You need a CAT scan of the chest, abdomen, pelvis, and you need an MRI brain and a PET scan.
Those are really the gold standards for determining clinical staging. In regards to pathologic staging, it’s really important to have tissue samplings. So, you biopsy a site of disease that’s concerning to you. If it looks like there’s only disease in the chest, you want to biopsy the site where there’s the tumor, and then you talk with your thoracic surgery or pulmonary team to determine the best way to sample the mediastinum for full staging.
Katherine Banwell:
Why is an accurate diagnosis so important?
Dr. Isabel Preeshagul:
So, an accurate diagnosis is so important because lung cancer is by no means black and white anymore. There are so many histologic subtypes that we are learning about. There are so many different molecular drivers that we are learning about. So, making sure you have the right diagnosis, full and next-generation sequencing testing, all of the imaging that you need could really make or break your treatment plan.
Katherine Banwell:
Dr. Preeshagul, let’s talk about biomarker testing. How is biomarker testing for lung cancer different from hereditary genetic testing?
Dr. Isabel Preeshagul:
So, we do do hereditary genetic testing for lung cancer patients as well. So, I think let’s backtrack a little bit. When you’re doing on a patient, there’s germline mutations and there’s somatic mutations. And germline mutations are mutations that you might get from Mom and Dad that they got from their parents and so on and so forth that you could give to your children or your brother and sister or whatever. So, that’s germline testing that could be passed along.
That would be like BRCA or any other APC gene, but we are learning more and more that there are mutations in lung cancer that do have a hereditary aspect to them. So, we are learning now that while we do somatic testing, which is to find a mutation that just spontaneously happened in your tumor all on its own, it’s really important to pair that with germline testing to make sure that there isn’t some kind of heritable mutation that’s also driving this lung cancer.
Katherine Banwell:
You mentioned hereditary genetic testing. Should family members of people with lung cancer undergo genetic testing then just to be reassured?
Dr. Isabel Preeshagul:
So, if there is a germline mutation, then they should – the family members should be referred to a geneticist to have that discussion.
Katherine Banwell:
What are common lung cancer biomarkers?
Dr. Isabel Preeshagul:
So, we have nine biomarkers within approval right now, but there are so many. There’s more than I could even talk about today. But some of the more common ones are EGFR, ALK, ROS1, MET exon 14. You have KRAS, KRAS-G12C, which is a newer one. We have NTRK. We have RET. The list goes on, HER2. I could talk for – there’s not enough time on this Zoom video to talk about all of the mutations. But there are nine mutations with approvals as of now to date, this very moment. That could change tomorrow.
Katherine Banwell:
Of course, it could. How do biomarkers in lung cancer affect treatment options for lung cancer patients?
Dr. Isabel Preeshagul:
So, it used to only be in stage IV, but now we are learning that biomarker testing is really important from the get-go because we have induction or neoadjuvant protocols that are looking at giving targeted therapy before patients go to surgery.
We know that there’s FDA approval for patients to get targeted therapy after surgery, and there’s a survival advantage there. So, make sure that you have next-generation sequencing testing regardless of your stage.
Katherine Banwell:
Okay. That’s good advice. So, we’ve heard how testing and a patient’s individual disease can lead to more targeted options. And you just mentioned targeted therapies. How do they work?
Dr. Isabel Preeshagul:
So, there’s many different targeted therapies that we have. Some of given as an infusion. For HER2, for example, we have TDXD, and we have T-DM1. TDXD is the only drug that’s FDA-approved in this setting. There are clinical trials looking at T-DM1. For EGFR Exon 20, we have another infusional drug called amivantamab (Rybrevant). For EGFR Exon 19 and Exon 21, we have a pill called osimertinib (Tagrisso). For KRAS, there’s a pill. For most of the driver alterations, it’s a pill, but some of them it does require infusional therapy.
But these are therapies that are targeted at the cells that harbor that mutation.
Katherine Banwell:
Let’s turn to immunotherapy. What is it, and how does it work?
Dr. Isabel Preeshagul:
So, immunotherapy is basically teaching your body to recognize cancer as foreign. So, when you have – I always kind of use this hand model. So, basically, a normal cell has, let’s say, three prongs. And then sometimes what happens is cancer will grow a marker called PD-L1 that makes it hide from the immune system. So, the body thinks that this is a normal cell. So, what immunotherapy does is it comes up and it sort of puts a cap on that PD-L1 so that the cell looks foreign again and the body can attack that cell and get rid of it. So, it’s almost like ramping up your immune system to recognize that marker and get rid of that cell.
Katherine Banwell:
What is the regimen for immunotherapy, and how often is treatment administered?
Dr. Isabel Preeshagul:
So, immunotherapy is approved in the neoadjuvant setting, which means before chemotherapy. It’s approved after chemotherapy, and it’s approved in the stage IV setting. There are many different regimens and many different dosings and many different drugs. But it’s typically given in your veins, either once every three weeks or once every four weeks for a certain amount of time. If it’s given in a curative setting and it’s given indefinitely or until there’s disease progression or intolerance in the stage IV setting.
Katherine Banwell:
Okay. Let’s touch upon the side effects of these types of treatment. You’ve mentioned that there are so many, but what are some of the major side effects, and how are they managed?
Dr. Isabel Preeshagul:
Side effects of immunotherapy can include pneumonitis, which is inflammation of the lungs, any kind of endocrinopathy like issues with your thyroid, issues with your pancreas like diabetes.
It can cause colitis, which is diarrhea, inflammation of the colon, hepatitis, inflammation of the liver. It can cause cerebritis, inflammation of the brain. It can cause arthritis or arthralgias, inflammation of the bones. And it can also cause rash and fatigue.
Typically, if it’s the thyroid, it’s managed with thyroid replacement hormone or a drug that would calm down the thyroid if it’s overactive. Pneumonitis is steroids. Hepatitis is sometimes treated with steroids. Colitis, steroids typically. Steroids usually come somewhere in there, usually not with the endocrinopathies, but the other itis’s, it’s typically – we start with steroids and go up from there. And the goal is to really recognize these toxicities before they become a problem and just at the glimmer of them just starting.
Katherine Banwell:
So, would you consider these treatments to be personalized medicine then?
Dr. Isabel Preeshagul:
So, it’s personalized in the sense that if someone has a high PD-L1 expression, there may be some data to demonstrate that they may benefit from immunotherapy or have a response. If someone can’t tolerate chemotherapy or is not interested in chemotherapy or has other reasons that may preclude them from getting it, it might be reasonable. So, in that sense, it is considered personalized.
Katherine Banwell:
How would you define personalized medicine?
Dr. Isabel Preeshagul:
To me, personalized medicine takes into account the biologic makeup of a patient’s disease like if they have a mutation and what their PD-L1 status is, what the histologic makeup of it. What’s their stage? And then, on the other hand, what’s important to that patient? If they’re a tailor, you want to make sure you’re not giving them a medication that’s going to cause neuropathy, so they can’t use their hands.
If they enjoy playing the harp or the piano, same thing. If their goal is to continue to run marathons, you may want to avoid something that’s going to cause inflammation of the lungs and risk them for pneumonitis. Tailoring to make sure that the treatment is part of their life but does not become their life.
Katherine Banwell:
If the test results don’t reveal one of the biomarkers you’ve been talking about, what other treatments are available?
Dr. Isabel Preeshagul:
So, if I don’t have an FDA approval, then sometimes we look to see if there is a clinical trial in our early phase drug development program, and we talk about a clinical trial. If there’s no clinical trial and I don’t have an FDA approval, then we have to talk about what options are considered standard of care and how to make that work into the patient’s lifestyle.
Katherine Banwell:
What about surgery? When is it used?
Dr. Isabel Preeshagul:
Surgery is typically used in the curative setting with early-stage disease. We’re really trying to give patients some kind of chemotherapy or some kind of treatment before they go to surgery. It’s shown to improve outcomes. It just gives us a en vivo view of how the tumor will respond to the treatment. So, we typically use surgery in the curative setting. And, at times, it’s appropriate to use surgery for a metastasectomy when you have one little site that’s growing. Sometimes after a tumor board discussion, it might be reasonable to resect that area.
Katherine Banwell:
Is radiation still used?
Dr. Isabel Preeshagul:
Same thing. It can be used in the curative setting, typically for patients with stage IIIB or stage IIIC disease and combined with chemotherapy patients that are not considered surgical candidates, or it’s used in the palliative setting when patients have painful metastases.
Katherine Banwell:
Would you define the B and C? You’ve mentioned that a couple of times.
Dr. Isabel Preeshagul:
Yeah.
Katherine Banwell:
We’re used to hearing Stage 1, 2, 3, 4. But what’s a stage IIIB and a stage IIIC?
Dr. Isabel Preeshagul:
Yeah. Sure. Sure. So, it does get a little bit into the weeds here about the size of the tumor and the amount of lymph nodes and location of the lymph nodes. But basically, stage IIIA is considered resectable. That means – that could be the size of the tumor with no lymph nodes, or it could be a smaller tumor with a lymph node on the same side as the disease. Stage IIIB would be a lymph node right underneath the windpipe at the station 7. And stage IIIB also includes lymph nodes that have crossed over to the contralateral side. And stage IIIC would be lymph nodes that are maybe up at the contralateral supraclavicular space.
Katherine Banwell:
Okay. Do treatment options change if the lung cancer returns?
Dr. Isabel Preeshagul:
Yes, they do change depending on if this is the same tumor type that’s come back. It’s typically a different treatment algorithm, yeah.
Katherine Banwell:
Okay. And should biomarker testing be done again if a relapse occurs?
Dr. Isabel Preeshagul:
100 percent. Because it guides everything about a patient’s treatment. It’s super important.
Katherine Banwell:
Okay. What are you excited about right now in lung cancer research?
Dr. Isabel Preeshagul:
I am excited and overwhelmed by the fact that we have so many approvals and so much exciting data that was just presented at ASCO and World Lung and ESMO that it’s next to impossible to keep up. And I’m happy that we have that problem, and I’m happy that the patients have – there’s a spotlight on lung cancer when we were in the shadows. And now, I think we have the spotlight.
And all of these approvals, you know, with it being Lung Cancer Awareness Month as well, I think is just so important. Just to make sure that we get the knowledge of these new approvals out there though, that is another struggle.
Katherine Banwell:
Well, are there any current clinical trials that look promising to you?
Dr. Isabel Preeshagul:
Yeah, I think there are many clinical trials. In the induction setting, there was some data that was just presented on ALINA looking at adjuvant alectinib (Alecensa). We just had a – we have approval for adjuvant osimertinib (Tagrisso) and the ADAURA trial.
But we are learning more and more that as these targeted therapies have approval in stage IV, we’re trialing them in stage III, and then we’re going to trial them in earlier stages and earlier settings. So, this has been the pattern of how drugs get approved. So, yes, there’s lots of exciting data coming through.
Katherine Banwell:
That’s excellent. Can you talk about antibody drug conjugates and where they fit into lung cancer care?
Dr. Isabel Preeshagul:
Yeah. That’s a great question. I don’t think anyone knows the answer as to where they fit in just yet.
We have probably over 300 antibody drug conjugates that are in development right now. And one of the more common ones that we use is trastuzumab deruxtecan (Enhertu), or TDXD, which is used in patients that harbor HER2 alterations in the stage IV lung cancer setting. It is basically almost like a Trojan horse. So, you have this antibody.
It’s typically IgG1, immunoglobulin. And then you have a linker, and then at the end of that linker is the warhead or the chemotherapy agent. So, the antibody comes in towards the cancer cell looking very innocent. It binds to the cancer cell. And, once it binds, then everyone inside the Trojan horse or this warhead rush into the cell and get to do its damage. So, it’s a totally different mechanism. We’re trying to outsmart some of the bypass mechanisms that cancer cells develop. And this may be the new wave, but stay tuned, more to come.
Katherine Banwell:
Right. So, it’s promising. How can patients find out more about current clinical trials?
Dr. Isabel Preeshagul:
So, you can always ask your healthcare practitioner if there are any clinical trials at the institution that you’re at, but clinicaltrials.gov has all the clinical trials that are available nationally and internationally.
You just type in your disease type. You can type in a couple keywords, EGFR maybe or ROS1 or stage IV, something along those lines, and then it should populate a list of clinical trials and what institutions have them open, if they’re still accruing or if they’re not, and a contact on that trial.
Katherine Banwell:
If a patient is interested in a clinical trial, what kinds of questions should they be asking their healthcare about the trial?
Dr. Isabel Preeshagul:
So, the first question to ask is, “Do we have any clinical trials that are appropriate for me?” If the answer is yes, “Are they appropriate for me now, or are they appropriate for me if what I’m on right now is not working?”
So, trying to figure out where that will be, and if they are appropriate for you now, how can I get evaluated, and how can we get things underway?
Katherine Banwell:
Yeah. What would you say to patients who are interested in participating in a clinical trial, but they’re nervous about it?
Dr. Isabel Preeshagul:
I think one thing that I love about being on a clinical trial is that there are more eyes are on you, because we are looking to get something approved, and we are just watching every single little granular detail. In a way, it’s almost like you’re being more micromanaged than if you were on standard of care because of just how many stops and checks there are, how many eyes are looking at your labs after the doctor and the nurse and the nurse practitioner, and the fellow take a look at everything. It’s 10 other people. So, it’s almost like it’s extra safe because of all of that. It’s exciting because you are hopefully getting tomorrow’s treatment today, right?
You’re trailblazing the way for other people after you. So, I think it’s exciting, but, of course, it’s nerve-wracking. It’s something new. You don’t know if it’s going to work. But I have to believe that the way that clinical trials are designed now and the clinical trials that we choose to open here, we really hope are going to be pushing the space forward.
Katherine Banwell:
Yeah. I’d like to get to a few questions that we received from audience members prior to the program. How do you help a family member that is an overwhelmed caregiver but refuses help? Any tips on how to provide support to this person?
Dr. Isabel Preeshagul:
I mean, I think we see caregiver burnout thousands of times a day, unfortunately, and the first thing is knowing how to recognize it. And the second most important thing is taking the time away from the visit with the patient to address the burnt-out caregiver, because there is not enough time in any visit to ever – there’s never enough time in my mind to spend with a patient.
I’m always pulled in a thousand different directions. And I think we all feel that. But taking the appropriate time to sit down and to say, “Hey. Listen. I recognize that you’re burnt out. I can see it. Who is in your corner helping you?” And just directing focus away from the patient just for a moment and to really focus on that caregiver and to rely on the social work team and the case manager and the support groups that your institution may have and to make sure that they know about those resources.
Katherine Banwell:
Yeah. Here’s another question we received. “Can you share more information regarding treatments available for stage IV lung cancer and their side effects?”
Dr. Isabel Preeshagul:
It depends on if this is non-small cell or small cell. It depends on if you have a driver alteration or not. So, I think that is a little bit challenging to talk about in just one session. But basically, you’re probably looking at some kind of targeted therapy if you have a mutation versus standard of care if you don’t have a targeted mutation versus a clinical trial. And I think those are kind of like the big baskets.
Katherine Banwell:
When is a second opinion necessary? Dr. Isabel Preeshagul: A second opinion is necessary anytime you want a second opinion.
Dr. Isabel Preeshagul:
There is no right or wrong time, any time. You’re just not jiving with your oncologist after the first day you met them, second opinion. You’re at the end of the line and you really want toknow more, second opinion. You’ve met two other doctors. You’re not jiving, third opinion. It’s always appropriate anytime you want.
Katherine Banwell:
So, the patient shouldn’t feel obligated to stay with that one provider?
Dr. Isabel Preeshagul:
Never. Never, never, never, never, never. No. Please don’t feel that way. There are no hard feelings. And, if there are, that’s not the right oncologist for you. It needs to feel like a perfect friendship. And, if it’s not that, it’s not the right thing.
Katherine Banwell:
Before we close, Dr. Preeshagul, I’d like to get your final thoughts. What would you say to the audience about the future of lung cancer care and treatment?
Dr. Isabel Preeshagul:
I do think that the future is bright because, as I mentioned, there is now this light that is shining in the lung cancer space. And things are getting approved. and discoveries are getting made faster than we can even keep up, which is exciting and overwhelming and daunting. But I am happy that, finally, this space is taking off, so I feel optimistic.
Katherine Banwell:
Okay. All right. Well, I wanna thank you so much for taking the time to join us today, Dr. Preeshagul.
Dr. Isabel Preeshagul:
Thank you so much for having me. These were wonderful questions, and I look forward to many more discussions with you. Thank you.
Katherine Banwell:
And thank you to all of our partners. To learn more about lung cancer and to access tools to help you become a proactive patient, visit powerfulpatients.org. I’m Katherine Banwell. Thanks for being with us today.
Gastric Cancer: How to Access the Best Care and Treatment for YOU
/in Gastric Cancer, Gastric Cancer Newly Diagnosed, Gastric Cancer Programs, Gastric Cancer Video ND, Gastrointestinal Cancer, GC Insist Treatment, INSIST! Gastric Cancer /by Kara RayburnGastric Cancer: How to Access the Best Care and Treatment for YOU from Patient Empowerment Network on Vimeo.
Advances in gastric cancer research have led to more personalized therapy for patients. Dr. Yelena Janjigian discusses how biomarker testing can help guide a patient’s prognosis and treatment path, reviews currently available gastric cancer therapies, and shares tips for self-advocacy.
Dr. Yelena Janjigian is Chief of Gastrointestinal Oncology Service at Memorial Sloan Kettering Cancer Center.
See More From INSIST! Gastric Cancer
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Transcript:
Katherine:
Hello and welcome. I’m your host, Katherine Banwell. Today’s program focuses on helping patients understand gastric cancer treatment options based on their individual disease. We’ll review the latest research and provide tips for self-advocacy to help patients access better care.
Before we meet our guest, let’s review a few important details. The reminder email that you received about this webinar contains a link to a program resource guide. If you haven’t already, click that link to access information to follow along during the webinar. At the end of this program, you’ll receive a link to a program survey. Please take a moment to provide feedback about your experience today in order to help us plan future webinars.
And finally, before we get into the discussion, please remember that this program is not a substitute for seeking medical advice. Please refer to your healthcare team about what might be best for you. Well, let’s meet our guest today. Joining me is Dr. Yelena Janjigian. Dr. Janjigian, welcome. Would you please introduce yourself?
Dr. Janjigian:
Thank you so much, Katherine, for this opportunity. My name is Yelena Janjigian. I’m a medical oncologist. And I oversee the GI oncology service at Memorial Sloan Kettering Cancer Center in New York. We’re a large group of doctors, over 40 physicians who treat everything from esophagus cancer to rectal cancer. And my research focus and my passion has been in developing new treatments for patients with stomach cancer, so I personally focus on this disease clinically and from research perspective.
Katherine:
Okay. Lovely.
Well, thank you so much for joining us today. I’d like to start by learning about the latest research news. Are there recent advances in gastric cancer that patients should know about?
Dr. Janjigian:
That’s a great question. The field of gastric cancer research has accelerated and evolved immensely over the last three years. We’ve had several important approvals for treatment of metastatic disease both for biomarkers selected population and immunotherapy targeted therapies. So, there’s been a lot of research, a lot of effort and some positive data that the patients and clinicians should be aware of.
Katherine:
And what excites you about the research you’re involved with?
Dr. Janjigian:
I’ve been focused on gastric cancer for nearly two decades. So, my recent advances have really helped to understand how we can improve patient’s survival better, potentially cure more patients, and understand the different subsets of cancer treatments and patients with gastric cancer understanding that not all gastric cancer is the same.
So, I think being able to zoom in on different subsets and target personalized approaches for each individual patient is why I stay in research, why I stay in gastric cancer research because we’ve been able to make some major breakthroughs.
Katherine:
That’s excellent news. How can patients stay up to date with treatment options?
Dr. Janjigian:
That’s a great question. And recently there’s been a lot of resources online through both the big pharma really educating patients with patient-friendly handouts. And many of my big recent papers when we publish them in big journals like Lancet or Lancet Oncology, for example, or JCO, there’s always a patient-friendly handout that comes with that data that helps patients understand some of the endpoints, how do we describe why this study is positive?
Or why is the FDA decided to approve the drug? So, there are many patient handouts that come with some of these papers. And it’s interesting, a lot of my patients come in. When they see me, they say, “Oh, it’s so good to finally meet you. I’ve watched a lot of your videos.” So, because of COVID actually, a lot of the scientific content that used to be just in in-person meetings behind doors for doctors, now it’s all online because a lot of these scientific presentations are now made for virtual content as well. So, patients have access to it. That’s double-edged sometimes. It’s a little bit of an information overload, and it may actually make patients feel more anxious than reassure them, right? Because it’s a lot of jargon and not too – but some patients find it helpful.
Katherine:
Yeah, I can see that. It can be a double-edged sword.
Dr. Janjigian:
Yeah.
Katherine:
Well, thank you for that advice. So, now that we’ve heard what’s happening in research, let’s review some more basic information about gastric cancer. First, gastric cancer is sometimes referred to as stomach cancer. Is that the same thing, or are both terms correct?
Dr. Janjigian:
Yeah. So, stomach is really where the cancer starts. But we can talk about stomach or abdomen. But gastric and stomach are the same tumor location basically. What’s interesting actually, some patients also have tumors that start at the bottom of their esophagus and extend into the stomach. So, biologically a lot of these cancers behave similarly. In fact, in United States the most common location for these cancers actually is in between the gastric esophageal junction and the stomach.
So, it’s in the location in of the cancer that’s at the very top of the stomach. But in short, stomach cancer and gastric cancer are interchangeable. And as I mentioned, for many of our viewers, actually gastro-esophageal junction is also part of the same disease.
Katherine:
Could you tell us what tests are used to diagnose gastric cancer?
Dr. Janjigian:
Most of our patients, when they come in to see me, by then the diagnosis of cancer has been made because I’m on oncologist.
In clinical practice, patients often present with vague symptoms or no symptoms at all. And that’s an important point for our clinicians to understand. In patients who have chronic acid reflux or have, for example, other risk factors such as H. pylori infection, often they end up getting endoscopy at the time, for example, for their first colonoscopy. So, the age of colonoscopy, the first colonoscopy has is getting earlier and earlier with each update, because colon cancer is increasing in incidents in younger adults. So, sometimes patients present and get first endoscopy, for example, which is an upper test with a camera when they’re getting their colonoscopies. In other patients, unfortunately, they present with more progressive symptoms. Often, it’s difficulty swallowing, regurgitation of food, and weight loss, which is obviously very dramatic.
And so they end up getting an endoscopy because of that and referred by their doctors.
Katherine:
How is gastric cancer staged? And what do the stages mean?
Dr. Janjigian:
Yeah. So, the most important part of the staging of gastric cancer and what patients ask me, “What is my risk of cancerous recurrence? What is my stage?” Really what it comes down to is the depth of invasion. So, it’s not only the size of the tumor, but how deep is it going into the muscle of the stomach, because stomach and your esophagus are basically a muscular bag, right? And so how deep is the invasion of the tumor into the wall? And also how likely are the lymph nodes to being involved? So, we assess it based on clinical symptoms such as swallowing difficulty and so forth. But in some patients, because the tumor is lower down in their stomach, they may not have very many symptoms, because there’s a lot more give in this muscular bag that our stomach is.
And so we test the endoscopic ultrasound to look at the depth of an invasion and also other X-ray type imaging such as a PET scan, a P-E-T scan or a CAT scan, which gives us a sense of tumor location whether or not we think the lymph nodes may be involved. And ultimately the final way to assess, especially in patients who are undergoing surgery, is their microscopic involvement of the lymph nodes? Because that often drives the likelihood of cancer coming back after surgery.
Katherine:
And how do the stages work for gastric cancer?
Dr. Janjigian:
So, in gastric cancer it’s either early, intermediate, or late stage. And this goes from stage I to IV. So, stage IV tumors is where most of the cancers are present. Over probably 50 percent of our patients present already at the time of diagnosis with more advanced stages.
Biologically this cancer just tends to move quickly. So, even in between endoscopies in patients who get endoscopies frequently, often it goes from 0 to stage III or IV because of the lymph node involvement and also spread of microscopic cells, right? Tiny, tiny cells before we even see them, they spread through the bloodstream to other organs or lymph nodes outside of your abdomen. So, that’s considered to be stage IV. And then early, early stage disease is stage I. Those usually that we can just scoop them out using endoscopic procedures. They don’t even need to have full surgery. And then stage II and III is usually if there’s some involvement of the tumor through the muscle or into the muscle of the stomach and also some lymph node involvement. But that’s how we stage it.
Katherine:
Okay. I’d like to move onto current gastric cancer treatment options. Can you provide an overview of what’s available now?
Dr. Janjigian:
Right. So, in patients with intermediate or early-stage tumors, really surgery is the main way to cure patients. Occasionally when we have an amazing response to chemotherapy or chemotherapy with immunotherapy or just immunotherapy, we can avoid surgery. But in most patients, surgery in early-stage disease is a gold standard for cure. Of course, it can be a very jarring thing to say to someone. “We have to take out. your stomach.” But patients do live without either fully their stomach removed or partially removed. And that’s the gold standard. We do additionally other treatments to help maximize chances of cure, but surgery is the main state. As I mentioned earlier, most of our patients, however, present with later stages where surgery is not feasible.
And when I say it’s not feasible, we would only attempt an operation if we thought there was a possibility of removing the cancer completely. Leaving some of the tumor behind, even if it’s only 1 percent of the cancer behind, makes patients unwell. They may not be able to tolerate additional chemo, so we do not recommend doing suboptimal surgery unless cancer can be completely removed. So, in those patients, we always explain the situation. And the disease is not potentially as curable, but it’s absolutely always treatable. And since the development of our immunotherapy options, really, we’ve changed the trajectory and the course of those cancers. We won’t know the stage or the final response to therapy until we’ve start it. But in those patients, usually a form of long-term therapy. Chronic treatment is very important.
And usually it involves a combination of chemotherapy and some targeted agents, biologic agents, meaning that they were designed in the lab to target the cancer specifically. And usually, they involve some sort of immunotherapy.
Katherine:
Excuse me. Can you go into some detail about the targeted therapies and immunotherapies that you use?
Dr. Janjigian:
Sure. So, conventional chemotherapy works on any rapidly dividing cell. And these are chemotherapies that have been tried and true in the clinic for decades, right? And they work still in gastric. And in particular they’re very important. And then over the last 10 years or so, we’ve started developing target agents in the lab that target the specific biologic tumor biomarkers. And when you think about tumor biomarkers, I would think about them as almost ZIP codes, right? How do you direct the cancer cell to die?
And how do you inhibit the cancer cell for the thing that is uniquely what’s making it grow as opposed to normal cells, right? So, that’s the difference between chemotherapy because chemotherapy can affect any rapidly dividing normal cell and cancer cell, while biologic agents ideally only affect the target, cancer, the cell. So, that’s why it’s very appealing to do both to help maximize response and survival on treatment. So, the biologic therapies that are available in and already approved in our disease for stomach cancer are something called HER2 directed treatments. And that’s been my focus in the lab. And then in my group has really spearheaded a lot of this research for HER2-positive tumors. In gastric cancer it occurs in up to 20 to 30 percent of tumors, but we have drugs such as trastuzumab or Herceptin, T-DXd, trastuzumab deruxtecan-nxki (Enhertu) or in HER2 that target these agents.
And furthermore, our work here at Memorial Sloan Kettering demonstrated the combination therapies really for HER2-positive disease has helped improve outcomes in those patients. So, that’s biologic therapy. Other biologic therapies that’s approved in gastric cancer is something called VEGFR-2 inhibitor. These are drugs that target blood vessel formation around the tumor to help the chemotherapy drugs work well and better. Those drugs are called ramucirumab or Cyramza. And that’s used in a combination of chemotherapy in second-line treatment. And there’s other drugs such as regorafenib (Stivarga) and other inhibitors that maybe have some targetable activity in our disease. And last but not the least is immunotherapy. So, immunotherapy’s a completely different class of drugs.
We think about immunotherapies, really the fundamental problem with cancer, right? The cancer issues that it started as a normal cell. So, at some point, it was a normal cell that then became and went awry and went rogue. And the body did not recognize that there was a problem. And the immune system did not eliminate that cancer cell. Before it started to metastasize and give us problems in their body, right? So, the fundamental question is why is the body’s immune system, why did it not recognize it as a abnormal cell? Well, because it really acts and looks like a normal cell from the immune perspective. Our immune system is trained not to hurt us, right? And that’s why in patients with rheumatoid arthritis or other autoimmune disorders, what happens is the immune system goes awry. So, what the immune checkpoint blockade or immunotherapy for cancer does, is it helps take some of those brakes off our immune system and help our immune system recognize the cancer and give it permission to say, “Hey, you know what?
You thought it was a normal cell. It’s not. It’s a cancer cell. Please help us eliminate it.” And that’s worked well because I think in for some of our patients, the immune system actually knows how to target and suppress the cancer much better than any of the fancy drugs we can design in the lab. And that’s why in some patients, immune checkpoint blockade immunotherapy has been such a game changer if you do respond, your duration and durability of response is so much more better than anything that would go to just done on our own in the lab or with other chemotherapies. So, it really is a nice way to think about it. And the patients feel like they’re part of the solutions. It’s always nice for them to have that.
But it’s been a real game changer for both HER2-positive and HER2-negative disease in combination with chemotherapy. I’ve had the pleasure of leading some of these studies. And it’s nice to be able to update the three or the four or the five-year survival rate from these studies in a disease where in the past most patients died within a year.
Katherine:
Dr. Janjigian, I’d like to talk about what goes into deciding on a best treatment for a patient. Is there testing that helps you understand a patient’s individual disease?
Dr. Janjigian:
One is an important factor about this disease, and when the patient comes in, the number one factor that helps us decide, what treatment to assign, is how well is the patient feeling? What are their nutritional deficits? How functional they are. Are they able to tolerate the treatment?
Because as an oncologist, the first rule is do no harm. Most patients come in when they’re first diagnosed are pretty well functional. They’re still able to eat. And so, they’re really up for the most aggressive. And that’s probably the number one wish I have from patients. I just want us to stay well and stay alive. So, we can be very aggressive with them, at least folks that come to see us in New York. And so, then the decision fork is really do you want only standard therapy, or are you interested in clinical trials? And I think what I am able to really explain to the patients, which is great, is that the benefit of trials – and, of course, you can never guarantee that a trial will be successful, right? Because that’s by definition – a clinical trial is experimental therapy. But for gastric cancer and stomach cancer where we need as many treatment options as possible, a clinical trial gives you an opportunity to try something different, and then go back to standard therapy, and then try experimental therapy, and then go back to standard therapy.
So, it gives you as many options as possible. The way that I help our patients visualize this is you’re trying to cross a very wide and somewhat turbulent river. And you need as many stepping stones as possible. And a clinical trial, if it makes sense for you and if you’re able to do it physically, it gives you that other option. The most important other factor is to understand which subset of stomach cancer you have, right? Because biomarker testing has helped us tremendously to advance this disease. If you look at and if you watch any of my talks, I usually have this timeline of therapeutic development in stomach cancer until really this past year.
We’re 2022, 2021. There was over a decade of negative trials, right? And the reason why I think is because the design of the trial really focused on targeting all the patients the same way. And now the trials are becoming more and more sophisticated. So, when we talk about the biomarker testing of the tumor, the patient’s specific tumor.
It’s important for the patient to ask their physician. “What is the status of my tumor?” And the four critical biomarkers are microsatellite instability, HER2, PD-L1, and Claudin-18.2. So, those four biomarkers have really helped us transform this field especially in patients with metastatic disease. And in all of the tertiary cancer centers, certainly here at Memorial Sloan Kettering, for each of the subsets we have a full research portfolio.
So the patients have both standard and experimental options available to them.
Katherine:
Well, how can test results like biomarker testing affect the patient’s prognosis and treatment options?
Dr. Janjigian:
It will depend on the treatment and how it is paired to the biomarkers. So, for example, a certain subset of tumors such as microsatellite and stable tumors are patients with PD-L1 high tumors or even patients with HER2-positive tumors. Now in clinical trials, we see that those patients have an outstanding dramatic response to combination therapies often with chemotherapy or immunotherapy together or even HER2 directed therapy with immunity therapy. So, it really will impact how likely your tumor is to shrink. And if the tumor is shrinking, and if you’re feeling better, obviously that translates to better survival.
Katherine:
Yeah. What questions should patients be asking about their test results?
Dr. Janjigian:
I think it’s important for patients to be very clear with their providers about their willingness to undergo repeated biopsies if needed.
I think the number one misunderstanding or misnomer that I see when patients come in to see me as a highly trained specialists, and they’re seeking me out for expertise and second and third and fourth opinions is that when the biomarker test is not done, often the answer in the community from the physician was, “Well, there was insufficient tissue or the tissue quality was not great, and that’s we’re going to do it. And it turns out the patient is perfectly willing and able to undergo a second biopsy. They really do not mind because a lot of times it’s just as simple as having a repeat endoscopy. Or even on treatment off and the problem is it’s a constantly evolving cancer. So, for example, if you receive first-line treatment and then you progressed and you need additional treatment, often it’s important to get a second biopsy to understand what your biomarkers are at that point.
And I described this to my patients. We can’t get into a battle with outdated maps. We need to know. And sometimes when there’s a misunderstanding, the doctors think, “Maybe the patient wouldn’t be willing to do it. Or they are risk-averse.” And the patient’s more than willing to do it. So, I think communicating your wishes and your intent clearly with your doctors and not being shy to ask questions, and also not being shy to seek out clinical trials, right? So, yesterday I was in clinic. I see a lot of this disease. I often see 30 patients at clinic. I had an 80-year-old patient in my clinic, right? And before you meet the patient, most doctors would think, “Well, it’s an elderly patient. They wouldn’t even be interested in clinical trials. What are we trying to accomplish here?”
Katherine:
Right.
Dr. Janjigian:
But this patient clearly is – he exercises five days a week. He’s extremely active. He wants the best options for him.
So, I am not an ageist, so I asked him. I said, “What are your sort of goals of this therapy? And how interested are you in clinical trials?” And him and the family were extremely enthusiastic. And, “We’re going to go for it, and we’re going to try.” So, I think having those conversations with your doctors – because you remember gastric cancer is very rare. In my clinic I see 30 patients, but in most normal sort of oncology practices, it’s lung, breast, and colon, the big three that sort of saturate the schedule of the oncologists. So, if they see one or two gastric cancers a month, they may not be thinking along the same lines of your disease. So, then you have to ask the questions of, “Are there any clinical trials? Should I see a specialist?” Did you do all of my biomarkers?
Katherine:
Yeah, yeah. That’s really great information to have.
Are there other decision factors involved in deciding on treatment options? You mentioned age, comorbidities. What else do you look at?
Dr. Janjigian:
Yeah, the other important factor as I said is nutrition. Being able to stay fit and stay independent is very important. Some of my patients ask me, and then they feel like what they eat is so important that as soon as they get their diagnosis, they restrict their diet. And then they start losing weight. And that’s not good. The number one negative prognostic factor is if you lose more than 10 percent of your body weight within the first few months of the diagnosis – because you get really weak, and then you can’t tolerate the chemotherapy. So, I tell the patients, “Your body will take from you whatever it wants. The cancer will take from you, from your body. So, you need to support yourself nutritionally.” So, if you don’t feel like eating a salad, but you are craving a cookie, it’s okay.
Have that cookie; just don’t lose weight. And I think that’s the number one. And also, the other factor is how do you communicate your diagnosis and your prognosis to your family and your friends? Because then everybody’s asking and making you in some ways anxious, your job. And what I tell patients is, “It’s on need-to-know basis.” If you find love and support, then you can tell people. Otherwise, you can just loosely kind of mention that you need some help, and you’re going through treatment without specific details. And the great part about these combination immunotherapies is that a lot of our functional patients actually continue to work through this. And so, we fill out whatever forms they need for their jobs and so forth. But we have lawyers that are continuing to work, teachers, and sometimes even construction workers. So, really, I would say make decisions as they come up.
Don’t run too far ahead and sort of assume that you’re going to not be well. But if you want to take some time off, that’s okay too. And so, I think the treatment paradigm for this disease has evolved so much that there’s a lot of misconceptions. And I think the job of a good oncologist is to let the patient live their life in as normal a fashion as possible. So, we work the chemo schedules around their schedule. Some of these immunotherapies you can give once a month. So, I have patients who will fly into see me, for example, get the dose, and then go back home. So, I think don’t be afraid to ask for what you need.
Katherine:
Yeah. Well, that leads us very smoothly into self-advocacy. And it’s really important that patients advocate for themselves. So, if a patient has a question or they’re unsure about a decision, why is it so important for them to speak up?
Dr. Janjigian:
What I always tell my patients and I explain to them, that often the doctors know a lot of information. But there’s so much information that it’s almost impossible to – and we only have 15 to 20 minutes together. So, it’s almost impossible to communicate everything that we know to you. So, you need to drive a bit of what the focus is of priorities in each visit and get as much information as you can. But also in some ways, follow the doctor’s lead. So, it’s a balance of information exchange. Use the portal as much as possible as well. The patient portal is often for follow-up questions. Write questions down. We have our nurse practitioners, our nurses, our fellows that continue to educate the patients because as things come up, and the field is so complicated that there are just so many things that you can ask at one single appointment.
So, it’s okay to forget something, but just write it down. In the end like anything else, you only have one sort of chance to do this in a way that you want it to be done. And as treatment progresses and you’re not feeling well, and maybe you don’t want to keep coming in for appointments and would rather go spend time in Aruba or Florida or somewhere sunny as opposed to – that’s okay. I think a lot of times it’s your life. You only have one. And I strongly believe in anything to try to get as much out of every interaction as possible using all the resources that are available to you.
Katherine:
Well, I’d like to close today with getting your thoughts on how you feel about the state of gastric cancer care. Are you hopeful about treatment options?
Dr. Janjigian:
I’m extremely hopeful. And usually, I finish all of my scientific talks. I’m a physician scientist.
I travel a lot to meetings. And my goal now in my career is to attract more and more young talent and scientists that will help us make the next wave of breakthroughs for this difficult disease. I think we’ve made a lot of progress, but the reality is: We’re still not curing enough patients. And so, our next wave is not just to stabilize and help people live longer but cure them definitively and permanently. And so, I finish every single presentation I have by how much the possibility and how fruitful this field has been. Personally, for my work and career of those that I’ve mentored throughout the years all over the world. So, I’m very hopeful for the next five, 10 years in this field. It will continue to get better.
Katherine:
It sounds very promising. Dr. Janjigian, thank you so much for joining us today.
Dr. Janjigian:
Thank you. Great question.
Katherine:
And thank you to all of our partners.
If you’d like to watch this webinar again, there will be a replay available soon. You’ll receive an email when it’s ready. And don’t forget to take the survey immediately following this webinar. It will help us as we plan future programs. To learn more about gastric cancer and to access tools to help you become a proactive patient, visit powerfulpatients.org. I’m Kathrine Banwell. It’s good to have you with us today.
Combination AML Therapy for Newly Diagnosed Patients | What Are the Long-Term Effects?
/in Acute Myeloid Leukemia, AML Newly Diagnosed, AML Programs, AML Thrive, AML Thrive Understanding, AML Treatments and Clinical Trials, AML Video ND, AML Video TC /by Kara RayburnCombination AML Therapy for Newly Diagnosed Patients | What Are the Long-Term Effects? from Patient Empowerment Network on Vimeo.
A Patient Empowerment Network community member wants to know the length of time that patients can stay on the combined treatment of azacitidine (Vidaza) and venetoclax (Venclexta). AML specialist Dr. Jacqueline Garcia responds, sharing an update on the long-term follow-up data for this combination treatment.
Dr. Jacqueline Garcia is an oncologist and AML researcher at the Dana-Farber Cancer Institute. Learn more about Dr. Garcia.
See More from Thrive AML
Related Resources:
New and Emerging AML Therapies Being Studied in Clinical Trials
Transcript:
Katherine Banwell:
Jerry had this question. “How long can patients stay on azacitidine (Vidaza) and venetoclax (Venclexta) before relapse or toxicities force them to abandon treatment?”
Dr. Jacqueline Garcia:
So, this is a good question. I would say azacitidine and venetoclax just got FDA-approved just shy of five years now, and it’s totally changed our treatment paradigm in many great ways. It was initially approved for patients that could not get intensive chemotherapies or were above 75. We call these our older patients, our more vulnerable.
And we demonstrated and compared to azacitidine alone. It was given with placebo. We saw that the combination of azacitidine and venetoclax not only was safe, well-tolerated, it led to two-and-a-half times higher complete remission rates and impressively longer survival. That’s all we care about, patients are living longer. So, one of the things that we are appreciating in 2023 now, now that we have more patients on azacitidine and venetoclax, is that we have many patients that are long-term responders.
So, in the original clinical trial we’ve been reported – and we just submitted the update for the long-term follow-up that we presented at the American Society of Hematology meeting in 2022, in December.
We presented the long-term follow-up data that shows that responses can be durable and even as long as two years or three years in some patients. The average amount of time the patients are on therapy is somewhere between one-and-a-half to two years. But not every patient performs like an average patient.
We have some that respond for less time. We have some that respond for a longer time. So, I definitely have a few patients that have been on combination therapy, and we’ve gone to year three, then four, and two that got to year five. And that was using the original indication of older the 75, no intensive chemotherapy. Most of those patients in the original trial and led to the approval were not transplant candidates. But once those drugs got approved, more patients that were older started getting this therapy.
And so, the durability of this treatment might be longer for people that don’t have competing health problems and for specific mutation subtypes. There are a couple of mutation subtypes that include IDH2 and NPM1, where we’ve seen some extreme long-term responders.
And then, there are others that are much shorter. So, I would say it’s very individual. In terms of toxicities in general, the regimens very well-tolerated. And if it’s not, often it’s because there should be supportive care, prophylaxis, and adjustments to the dosing strategy, which has been well-published. Sometimes, if you have a treating oncologist that is less familiar, they won’t know the nuances of how to adjust the doses, so I would ask your local oncologist to reach out to anybody that was part of the original trials. Often, a lot of us are very responsive to helping out our colleagues to help patients to stay on treatment.
But at the end of the day, if a patient loses response or has a bad toxicity that makes it very difficult, we have to move on to another therapy.
Thrive CAR T-Cell Therapy Resource Guide
/in MM Newly Diagnosed, MM Resources ND, MM Resources TC, MM Thrive CAR T, MM Thrive CAR T Guides, MM Treatments and Clinical Trials, Multiple Myeloma /by Kara RayburnDownload Resource Guide
PEN-186_ThriveCART_Guide
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Thriving with an Myeloproliferative Neoplasm (MPN) Resource Guide
/in MPN Newly Diagnosed, MPN Programs, MPN Resources ND, MPN Resources TC, MPN Resources WPS, MPN Treatments and Clinical Trials, MPN Whole Patient Support, Myeloproliferative Neoplasms, Thrive MPN, Thrive MPN Guides /by Kara RayburnDownload Resource Guide
PEN-187_MPNThrive2023_Guide
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Elevating Cancer Advocacy: 10 Strategies for Effective Information Dissemination
/in Patient Empowerment, PEN Blog /by Marie Ennis-O'ConnorAs patient advocates we not only want to educate and support cancer research and awareness, but we also want to inspire hope. In this month’s article, I discuss 10 types of content that can help you communicate and disseminate information, advance cancer advocacy, and encourage and empower those affected by cancer.
1. Treatment Journey Timelines
Share informative timelines outlining the typical journey of a cancer patient from diagnosis to treatment and recovery.
What to share:
2. Visual Content
Use graphics, videos, or infographics to make your content more visually appealing The human brain processes visual information much faster than text, making visual content not only more engaging but also more memorable. In addition to enhancing understanding and engagement, visual content is more likely to be shared across various social media platforms. People are more likely to share visually appealing and informative content with their networks, contributing to the dissemination of important medical information.
What to share:
3. Personal Stories
Use written narratives, images, and video testimonials to describe the emotional and physical effects of being diagnosed with cancer.
What to share:
4. Cancer Prevention Tips
As a cancer advocate, your aim is not only to raise awareness but also to empower others with practical advice that promotes a proactive approach to wellness and reduces the risk of cancer.
What to share:
5. Clinical Trial Information
Clinical trials often explore novel treatments that may be more effective than standard therapies. By sharing information about ongoing trials, you can open doors for patients to access innovative and potentially transformative medical interventions.
What to share:
6. Legislation and Policy Updates
By sharing legislative changes related to cancer research funding, healthcare policies, and patient rights, you can empower individuals facing a cancer diagnosis, ensuring that they are aware of their rights and can actively participate in their treatment decisions.
What to share:
7. Conference Reports
Conference reporting facilitates the dissemination of the latest research, treatment updates, and policy discussions to a broader audience, which is a crucial aspect of cancer advocacy.
What to share:
8. Cancer Awareness Days, Weeks, and Months
Compile a list of key cancer-related awareness days, weeks, or months throughout the year. These designated days are important for educating the public, destigmatizing the disease, and advocating for essential research funding. Integrate these awareness days into your content calendar, dedicating specific time frames for planning, creating, and promoting content around each designated date.
What to share
9. Think Beyond Cancer
Thinking beyond cancer-specific days and aligning your advocacy efforts with impactful occasions like International Women’s Day can broaden the scope of your message and connect with a wider audience.
What to share:
9. Interactive Content
By incorporating interactive content, such as online polls, information can be shared in a more dynamic and engaging way. Audiences are not only educated but also engaged and mobilized through a two-way interaction.
What to share:
I hope you’ve found these content suggestions helpful. Implementing these ideas can not only raise awareness about cancer but also inspire action, foster community, and contribute significantly to the advancement of cancer advocacy.
You might also like to read
The Patient Advocate’s Guide to Social Media Content Planning – Patient Empowerment Network (powerfulpatients.org)
Transforming Your Social Media Presence: 5 Steps to Foster Inclusivity and Advocate for All – Patient Empowerment Network (powerfulpatients.org)
November 2023 Digital Health Round Up
/in PEN Blog /by Kara RayburnScientists and researchers are using technology to advance the fight against cancer, inventing machines to help with prevention and treatment of the disease. A simple finger stick test has been developed to help brain cancer patients monitor for recurrence from home. Scientists have invented a machine to help produce T cells quickly for immunotherapy treatments. A non-invasive device that uses ultrasound waves offers hope for liver cancer treatment.
Finger-Prick Test Could Help Spot Brain Cancer Recurrence Sooner
Scientists at University of Sheffield and Nottingham Trent University are developing the world’s first finger-prick test to spot brain tumors. More than 300,000 people worldwide are diagnosed with brain cancer each year, and while treatments have improved over the last few decades, recurrence remains a risk. It is a finger-prick test using medical technology of the lateral flow test. This test is easy to use and affordable. It can detect molecules in the blood that are specific to the patient’s tumor so it can catch recurrence early. The risk of brain cancer recurring is significant and can aggressively spread if not caught early. Instead of MRI ‘s every six months, this simple test could be done weekly, at home, to monitor for the cancer coming back.
Machine Can Quickly Produce Needed Cells for Cancer Treatment
In the journal Biotechnology Progress, Washington State University researchers have reported that they developed a mini-fridge sized bioreactor that is able to manufacture the cells, called T cells, at 95% of the maximum growth rate about 30% faster than current technologies. These T cells can be used for immunotherapy treatment to help fight cancer. Cart therapy can be challenging due to the cost and time required to grow the amount of T cells needed. Scientists applied 40 years of research, made this bioreactor using centrifugal force to grow the cells. It is made with a sterile cabinet so it can be used in a bigger variety of circumstances. The scientist’s goal is to make enough cells for three treatments immunotherapy within three days.
This Non-Invasive Device Blasts Apart Tumors with Sound Waves
This week, the US Food and Drug administration gave the green light to a device that uses ultrasound waves to blast apart tumors in the liver. This technique, which requires no needles, injections, knives, or drugs, it’s called histotripsy, and it’s being developed by a company called HistoSonics. This machine sends high energy ultrasound waves to the tumor and that action makes micro bubbles. When the micro bubbles breakdown, it stresses the tumor cells, causing the tumor to break apart. The small bits are then taken out by the patient’s own immune system, which in turn helps the immune system recognize and remember the cancer cells to help prevent recurrence. The whole process is painless with a faster recovery time. This machine uses imaging and a robotic arm for a more precise aim, saving more healthy tissue.
Non-Small Cell Lung Cancer Treatment | Clinical Trials and Research Updates
/in INSIST! Lung Cancer, LC Insist Treatment, LC Newly Diagnosed, LC Programs, LC Testing, LC Videos ND, LC Videos T, Lung Cancer /by Kara RayburnNon-Small Cell Lung Cancer Treatment | Clinical Trials and Research Updates from Patient Empowerment Network on Vimeo.
What are the latest advances in lung cancer care? Lung cancer specialist Dr. Isabel Preeshagul shares highlights from recent conferences, promising clinical trial updates, and advice for people interested in joining clinical trials.
Dr. Isabel Preeshagul is a thoracic medical oncologist at Memorial Sloan Kettering Cancer Center. Learn more about Dr. Preeshagul.
See More From INSIST! Lung Cancer
Related Resources:
Understanding Currently Available Non-Small Cell Lung Cancer Treatments
Non-Small Cell Lung Cancer Treatment Options | Personalizing Therapy
What Essential Testing Reveals About Your Non-Small Cell Lung Cancer
Transcript:
Katherine Banwell:
What are you excited about right now in lung cancer research?
Dr. Isabel Preeshagul:
I am excited and overwhelmed by the fact that we have so many approvals and so much exciting data that was just presented at ASCO and World Lung and ESMO that it’s next to impossible to keep up. And I’m happy that we have that problem, and I’m happy that the patients have – there’s a spotlight on lung cancer when we were in the shadows. And now, I think we have the spotlight.
And all of these approvals, you know, with it being Lung Cancer Awareness Month as well, I think is just so important. Just to make sure that we get the knowledge of these new approvals out there though, that is another struggle.
Katherine Banwell:
Well, are there any current clinical trials that look promising to you?
Dr. Isabel Preeshagul:
Yeah, I think there are many clinical trials. In the induction setting, there was some data that was just presented on ALINA looking at adjuvant alectinib (Alecensa). We just had a – we have approval for adjuvant osimertinib (Tagrisso) and the ADAURA trial.
But we are learning more and more that as these targeted therapies have approval in stage IV, we’re trialing them in stage III, and then we’re going to trial them in earlier stages and earlier settings. So, this has been the pattern of how drugs get approved. So, yes, there’s lots of exciting data coming through.
Katherine Banwell:
That’s excellent. Can you talk about antibody drug conjugates and where they fit into lung cancer care?
Dr. Isabel Preeshagul:
Yeah. That’s a great question. I don’t think anyone knows the answer as to where they fit in just yet.
We have probably over 300 antibody drug conjugates that are in development right now. And one of the more common ones that we use is trastuzumab deruxtecan (Enhertu), or TDXD, which is used in patients that harbor HER2 alterations in the stage IV lung cancer setting. It is basically almost like a Trojan horse. So, you have this antibody.
It’s typically IgG1, immunoglobulin. And then you have a linker, and then at the end of that linker is the warhead or the chemotherapy agent. So, the antibody comes in towards the cancer cell looking very innocent. It binds to the cancer cell. And, once it binds, then everyone inside the Trojan horse or this warhead rush into the cell and get to do its damage. So, it’s a totally different mechanism. We’re trying to outsmart some of the bypass mechanisms that cancer cells develop. And this may be the new wave, but stay tuned, more to come.
Katherine Banwell:
Right. So, it’s promising. How can patients find out more about current clinical trials?
Dr. Isabel Preeshagul:
So, you can always ask your healthcare practitioner if there are any clinical trials at the institution that you’re at, but clinicaltrials.gov has all the clinical trials that are available nationally and internationally.
You just type in your disease type. You can type in a couple keywords, EGFR maybe or ROS1 or stage IV, something along those lines, and then it should populate a list of clinical trials and what institutions have them open, if they’re still accruing or if they’re not, and a contact on that trial.
Katherine Banwell:
If a patient is interested in a clinical trial, what kinds of questions should they be asking their healthcare about the trial?
Dr. Isabel Preeshagul:
So, the first question to ask is, “Do we have any clinical trials that are appropriate for me?” If the answer is yes, “Are they appropriate for me now, or are they appropriate for me if what I’m on right now is not working?”
So, trying to figure out where that will be, and if they are appropriate for you now, how can I get evaluated, and how can we get things underway?
Katherine Banwell:
Yeah. What would you say to patients who are interested in participating in a clinical trial, but they’re nervous about it?
Dr. Isabel Preeshagul:
I think one thing that I love about being on a clinical trial is that there are more eyes are on you, because we are looking to get something approved, and we are just watching every single little granular detail. In a way, it’s almost like you’re being more micromanaged than if you were on standard of care because of just how many stops and checks there are, how many eyes are looking at your labs after the doctor and the nurse and the nurse practitioner, and the fellow take a look at everything. It’s 10 other people. So, it’s almost like it’s extra safe because of all of that. It’s exciting because you are hopefully getting tomorrow’s treatment today, right?
You’re trailblazing the way for other people after you. So, I think it’s exciting, but, of course, it’s nerve-wracking. It’s something new. You don’t know if it’s going to work. But I have to believe that the way that clinical trials are designed now and the clinical trials that we choose to open here, we really hope are going to be pushing the space forward.
Non-Small Cell Lung Cancer Treatment Options | Personalizing Therapy
/in INSIST! Lung Cancer, LC Insist Treatment, LC Newly Diagnosed, LC Programs, LC Testing, LC Videos ND, LC Videos T, Lung Cancer /by Kara RayburnNon-Small Cell Lung Cancer Treatment Options | Personalizing Therapy from Patient Empowerment Network on Vimeo.
How does the presence of biomarkers impact lung cancer treatment options? Lung cancer specialist Dr. Isabel Preeshagul discusses how test results may influence treatment options and aid in personalizing lung cancer therapy.
Dr. Isabel Preeshagul is a thoracic medical oncologist at Memorial Sloan Kettering Cancer Center. Learn more about Dr. Preeshagul.
See More From INSIST! Lung Cancer
Related Resources:
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What Biomarkers Affect Lung Cancer Care and Treatment?
Lung Cancer Care Decisions | Advice for Self-Advocacy
Transcript:
Katherine Banwell:
How do biomarkers in lung cancer affect treatment options for lung cancer patients?
Dr. Isabel Preeshagul:
So, it used to only be in stage IV, but now we are learning that biomarker testing is really important from the get-go because we have induction or neoadjuvant protocols that are looking at giving targeted therapy before patients go to surgery.
We know that there’s FDA approval for patients to get targeted therapy after surgery, and there’s a survival advantage there. So, make sure that you have next-generation sequencing testing regardless of your stage.
Katherine Banwell:
Okay. That’s good advice. So, we’ve heard how testing and a patient’s individual disease can lead to more targeted options. And you just mentioned targeted therapies. How do they work?
Dr. Isabel Preeshagul:
So, there are many different targeted therapies that we have. Some of given as an infusion. For HER2, for example, we have TDXD, and we have T-DM1. TDXD is the only drug that’s FDA-approved in this setting. There are clinical trials looking at T-DM1. For EGFR Exon 20, we have another infusional drug called amivantamab-vmjw (Rybrevant). For EGFR Exon 19 and Exon 21, we have a pill called osimertinib (Tagrisso). For KRAS, there’s a pill. For most of the driver alterations, it’s a pill, but some of them it does require infusional therapy. But these are therapies that are targeted at the cells that harbor that mutation.
Katherine Banwell:
Let’s turn to immunotherapy. What is it, and how does it work?
Dr. Isabel Preeshagul:
So, immunotherapy is basically teaching your body to recognize cancer as foreign. So, when you have – I always kind of use this hand model. So, basically, a normal cell has, let’s say, three prongs. And then sometimes what happens is cancer will grow a marker called PD-L1 that makes it hide from the immune system. So, the body thinks that this is a normal cell. So, what immunotherapy does is it comes up and it sort of puts a cap on that PD-L1 so that the cell looks foreign again and the body can attack that cell and get rid of it. So, it’s almost like ramping up your immune system to recognize that marker and get rid of that cell.
Katherine Banwell:
What is the regimen for immunotherapy, and how often is treatment administered?
Dr. Isabel Preeshagul:
So, immunotherapy is approved in the neoadjuvant setting, which means before chemotherapy. It’s approved after chemotherapy, and it’s approved in the stage IV setting. There are many different regimens and many different dosings and many different drugs. But it’s typically given in your veins, either once every three weeks or once every four weeks for a certain amount of time. If it’s given in a curative setting and it’s given indefinitely or until there’s disease progression or intolerance in the stage IV setting.
Katherine Banwell:
Okay. Let’s touch upon the side effects of these types of treatment. You’ve mentioned that there are so many, but what are some of the major side effects, and how are they managed?
Dr. Isabel Preeshagul:
Side effects of immunotherapy can include pneumonitis, which is inflammation of the lungs, any kind of endocrinopathy like issues with your thyroid, issues with your pancreas like diabetes.
It can cause colitis, which is diarrhea, inflammation of the colon, hepatitis, inflammation of the liver. It can cause cerebritis, inflammation of the brain. It can cause arthritis or arthralgias, inflammation of the bones. And it can also cause rash and fatigue.
Typically, if it’s the thyroid, it’s managed with thyroid replacement hormone or a drug that would calm down the thyroid if it’s overactive. Pneumonitis is steroids. Hepatitis is sometimes treated with steroids. Colitis, steroids typically. Steroids usually come somewhere in there, usually not with the endocrinopathies, but the other itis’s, it’s typically – we start with steroids and go up from there. And the goal is to really recognize these toxicities before they become a problem and just at the glimmer of them just starting.
Katherine Banwell:
So, would you consider these treatments to be personalized medicine then?
Dr. Isabel Preeshagul:
So, it’s personalized in the sense that if someone has a high PD-L1 expression, there may be some data to demonstrate that they may benefit from immunotherapy or have a response. If someone can’t tolerate chemotherapy or is not interested in chemotherapy or has other reasons that may preclude them from getting it, it might be reasonable. So, in that sense, it is considered personalized.
Katherine Banwell:
How would you define personalized medicine?
Dr. Isabel Preeshagul:
To me, personalized medicine takes into account the biologic makeup of a patient’s disease like if they have a mutation and what their PD-L1 status is, what the histologic makeup of it. What’s their stage? And then, on the other hand, what’s important to that patient? If they’re a tailor, you want to make sure you’re not giving them a medication that’s going to cause neuropathy, so they can’t use their hands.
If they enjoy playing the harp or the piano, same thing. If their goal is to continue to run marathons, you may want to avoid something that’s going to cause inflammation of the lungs and risk them for pneumonitis. Tailoring to make sure that the treatment is part of their life but does not become their life.
What Essential Testing Reveals About Your Non-Small Cell Lung Cancer
/in INSIST! Lung Cancer, LC Insist Testing, LC Newly Diagnosed, LC Programs, LC Testing, LC Videos ND, LC Videos T, Lung Cancer /by Kara RayburnWhat Essential Testing Reveals About Your Non-Small Cell Lung Cancer from Patient Empowerment Network on Vimeo.
What do lung cancer test results reveal to your healthcare team about your disease? Dr. Isabel Preeshagul provides an overview of essential testing for lung cancer and explains the difference between germline and somatic mutations.
Dr. Isabel Preeshagul is a thoracic medical oncologist at Memorial Sloan Kettering Cancer Center. Learn more about Dr. Preeshagul.
See More From INSIST! Lung Cancer
Related Resources:
Non-Small Cell Lung Cancer Treatment Options | Personalizing Therapy
Non-Small Cell Lung Cancer Treatment | Clinical Trials and Research Updates
Transcript:
Katherine Banwell:
I’d like to turn to the clinical side of non-small cell lung cancer. What tests help you identify the type and stage of lung cancer?
Dr. Isabel Preeshagul:
Obviously, you need a CAT scan. You need a CAT scan of the chest, abdomen, pelvis, and you need an MRI brain and a PET scan.
Those are really the gold standards for determining clinical staging. In regards to pathologic staging, it’s really important to have tissue samplings. So, you biopsy a site of disease that’s concerning to you. If it looks like there’s only disease in the chest, you want to biopsy the site where there’s the tumor, and then you talk with your thoracic surgery or pulmonary team to determine the best way to sample the mediastinum for full staging.
Katherine Banwell:
Why is an accurate diagnosis so important?
Dr. Isabel Preeshagul:
So, an accurate diagnosis is so important, because lung cancer is by no means black and white anymore. There are so many histologic subtypes that we are learning about. There are so many different molecular drivers that we are learning about. So, making sure you have the right diagnosis, full and next-generation sequencing testing, all of the imaging that you need could really make or break your treatment plan.
Katherine Banwell:
Dr. Preeshagul, let’s talk about biomarker testing. How is biomarker testing for lung cancer different from hereditary genetic testing?
Dr. Isabel Preeshagul:
So, we do do hereditary genetic testing for lung cancer patients as well. So, I think let’s backtrack a little bit. When you’re doing on a patient, there are germline mutations and there are somatic mutations. And germline mutations are mutations that you might get from Mom and Dad that they got from their parents and so on and so forth that you could give to your children or your brother and sister or whatever. So, that’s germline testing that could be passed along.
That would be like BRCA or any other APC gene, but we are learning more and more that there are mutations in lung cancer that do have a hereditary aspect to them. So, we are learning now that while we do somatic testing, which is to find a mutation that just spontaneously happened in your tumor all on its own, it’s really important to pair that with germline testing to make sure that there isn’t some kind of heritable mutation that’s also driving this lung cancer.
Katherine Banwell:
You mentioned hereditary genetic testing. Should family members of people with lung cancer undergo genetic testing then just to be reassured?
Dr. Isabel Preeshagul:
So, if there is a germline mutation, then they should – the family members should be referred to a geneticist to have that discussion.
Katherine Banwell:
What are common lung cancer biomarkers?
Dr. Isabel Preeshagul:
So, we have nine biomarkers within approval right now, but there are so many. There’s more than I could even talk about today. But some of the more common ones are EGFR, ALK, ROS1, MET exon 14. You have KRAS, KRAS-G12C, which is a newer one. We have NTRK. We have RET. The list goes on, HER2. I could talk for – there’s not enough time on this Zoom video to talk about all of the mutations. But there are nine mutations with approvals as of now to date, this very moment. That could change tomorrow.
Insist on Better Lung Cancer Care | Tips for Essential Communication
/in INSIST! Lung Cancer, LC Insist Treatment, LC Newly Diagnosed, LC Programs, LC Testing, LC Videos ND, LC Videos T, Lung Cancer /by Kara RayburnInsist on Better Lung Cancer Care | Tips for Essential Communication from Patient Empowerment Network on Vimeo.
How can you advocate for the best lung cancer care? Lung cancer specialist Dr. Isabel Preeshagul provides an overview of lung cancer healthcare team members, reviews how treatment goals are determined, and shares advice for communication with your care team.
Dr. Isabel Preeshagul is a thoracic medical oncologist at Memorial Sloan Kettering Cancer Center. Learn more about Dr. Preeshagul.
See More From INSIST! Lung Cancer
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Understanding Currently Available Non-Small Cell Lung Cancer Treatments
Transcript:
Katherine Banwell:
I’d like to start with a question pertaining to our series title, Insist. Why is it essential for patients to collaborate with their providers on care treatment decisions?
Dr. Isabel Preeshagul:
So, collaborating is so important, right? I always tell my patients this is not a dictatorship, right? This is a collaborative effort where I’m here to guide you, but you are the captain of the ship.
You are the one that needs to make all of the decisions, and I’m here to make sure that the ship goes in a smooth direction, so making sure we have open lines of communication that the patients and their caregivers feel comfortable talking to me and my team and also vice versa and that we trust each other. It’s so important because we are going for a marathon, right? We’re not going for a sprint. This is a long-term relationship, whether we’re treating for cure or we’re treating you with palliative intent and it’s treatable but not curable. We’re going to be following with each other for a long time.
Katherine Banwell:
A lung cancer healthcare team, of course, consists of a number of different providers. Would you tell us about the various members on a team?
Dr. Isabel Preeshagul:
Sure. So, there is – there are the people that do the scheduling, that make sure that the CAT scan is scheduled, that the MRI is done, your chemo gets scheduled, all of that. The schedulers are super important and an integral part of our team.
And then we also have our office coordinators that answers the phone calls and passes along the messages and assists with scheduling and sort of sets expectations and is the face of the practice. Then you have an office practice nurse or an oncology practice nurse who is the doctor’s right hand, making sure that the patients get proper chemotherapy teaches, making sure that they understand about possible side effects, risks versus benefits, making sure medications are up to date, assessing symptoms.
They are sort of the front line when it comes to any patient call they’re triaging, and they’re escalating or deescalating. That would be the office practice nurse. And then you have an advanced care practitioner, an APP. You either have a nurse practitioner or a PA that’s working with you that’s sometimes seeing patients independently, sometimes putting chemotherapy orders, you know, really serving as almost as another doctor.
If for some reason there is something that the doctor’s not available to do, the doctor needs in a pinch, or my patients that are almost at long-term follow-up that are doing great that are just kind of coasting, I will share with my NP and make sure that they know her just as well as they know me. And sometimes there’s a fellow, or there’s a resident or there’s a med student that’s part of the team as well because see one, do one, teach one. It’s really important to teach those that are coming after you and serve as mentors and really include them in part of the team and part of the decision-making. And then you have the doctor that just kind of oversees everything.
Katherine Banwell:
Of course. How would you define treatment goals for people with lung cancer?
Dr. Isabel Preeshagul:
So, the goal of treatment, I think, is really contingent upon someone’s stage, but it’s also contingent upon what’s important to the patient, right? So, we have patients that are stage I all the way to stage IIIC that we treat with intention to cure.
And patients that have stage IV disease, it’s treatable but not curable. So, I am very transparent with that as long as I have the information to have that discussion. With that being said, there are some patients with stage III disease or stage I disease that don’t really want treatment and want to focus on quality of life. And that’s okay too. And in which case, you know, at some point, their cancer will likely progress. How quickly or when that will happen, we don’t know. Could they pass from something else? It’s possible. But you really need to talk about what’s important to the patient, because it’s not always cut and dry.
Katherine Banwell:
As you mentioned, Dr. Preeshagul, there are several different support members on a team. What would you say to patients or even care partners who can sometimes feel like they’re bothering their healthcare team with their questions and comments?
Dr. Isabel Preeshagul:
So, we do get that concern a lot. And I always say, “I’m here for you 24/7. And, if it’s not me, it’s someone that’s just as qualified to answer your questions no matter what.”
“And I would rather get a phone call at 3:00 a.m. than get a phone call at 9:00 a.m., and you need to go to the hospital right now or God forbid something happened. I get a phone call from someone in the ICU that you went overnight and terrible things happened. So, I want the phone calls to come through to keep you out of the hospital and keep you from going south. So, call me.” And I never try to – I don’t try to outline contingency plans or criteria of what would warrant a call, because then you end up getting in trouble.
I always just tell my patient, “Think about how you’re feeling now in front of me. If you’re feeling any different than how you feel at this very moment, call me.”
INSIST! Non-Small Cell Lung Cancer Resource Guide
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PODCAST: Thrive | Advice for Managing Potential CAR T-Cell Therapy Side Effects
/in Empowered! Podcast, MM Newly Diagnosed, MM Podcasts ND, MM Podcasts TC, MM Treatments and Clinical Trials, Multiple Myeloma, PEN Blog /by Kara RayburnDr. Adriana Rossi, a myeloma expert and researcher, discusses how CAR T-cell therapy has revolutionized care, the process for undergoing this therapy, common side effects of this treatment, and advice for patients considering this option. Dr. Rossi also shares updates in CAR T-cell therapy research and explains what she’s excited about in myeloma care.
Dr. Adriana Rossi is Co-director of the CAR T and stem cell transplant program at the Center for Excellence for Multiple Myeloma at Mount Sinai Health System in New York City. Learn more about Dr. Rossi.
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See More From Thrive CAR T-Cell Therapy
Transcript:
Katherine Banwell:
Hello, and welcome. I am your host, Katherine Banwell. Today’s program is part of our Thrive series, where we will discuss what to expect and how to manage side effects of CAR T-cell therapy.
Before we get into the discussion, please remember that this program is not a substitute for seeking medical advice. Please refer to your healthcare team about what might be best for you.
Well, let’s meet our guest today. Joining us is Dr. Adriana Rossi. Dr. Rossi, welcome. Would you please introduce yourself?
Dr. Adriana Rossi:
Thank you so much. I am one of the codirectors of the CAR T program at Mount Sinai in New York City and thrilled to be with you today.
Katherine Banwell:
Thank you. Since we’ll be discussing the ins and outs of CAR T-cell therapy, I thought we could start with your perspective as a researcher in the field. How has this therapy revolutionized myeloma care?
Dr. Adriana Rossi:
It absolutely has. And I would say in time we’ve had – this is now our fourth revolution. Stem cell transplants was the first time we actually achieved what we call a complete remission in at least a few patients, making myeloma disappear.
Then, we had the second revolution with the novel agents. Now, we had drug therapies that were giving us these complete remission still at about a 30 percent rate. And then, the monoclonal antibodies were the most recent revolution. And currently, we are in what we call the T-cell redirection.
It really has been driven by CAR T-cell therapies and something we call bispecific antibodies, which also use your patient’s T cells to kill the myeloma. We are now seeing absolutely unprecedented response rates, meaning almost everybody is responding. Also, depth of response, which we have really learned over time is a way to translate into long remissions. So, every long, very significant remissions. And the early data in patients who have had many prior lines.
Katherine Banwell:
So, it is very encouraging news.
Dr. Adriana Rossi:
It is very encouraging.
Katherine Banwell:
Let’s start with an overview of CAR T-cell therapy. Could you explain how the treatment works?
Dr. Adriana Rossi:
Absolutely. So, CAR T specifically is speaking to T cells, which are a normal part of the immune system that have been engineered and modified. So, normal part of the immune system T cells have a lot of checks and balances and are constantly looking for cells that are supposed to be killed. For example, something that has a virus in it.
When we engineer the CAR T-cells, we modify, one, the target so they are now trained to find the specific target on a tumor cell. And we remove all these checks and balances. So, once that T-cell finds its target, it can kill it without all of the side effects. The way normal T cells communicate with other members of the immune system are something called cytokines. So, we will touch on that a little later, I think, but we also, again, interfere with that communication by engineering the cells.
Katherine Banwell:
Which patient type qualifies for CAR T?
Dr. Adriana Rossi:
In 2023, we currently have two approved commercial CAR T products and we do have a number of them in clinical trials. The two that are commercially approved specifically are targeted for patients who are in their fourth line of therapy, so the myeloma has learned to come back that four times.
They’ve been exposed to all of the regular drugs, which by four lines most patients will have been at least once. We look for patients whose kidney function is at a safe level to tolerate the therapy. And other than that, it’s really having caregiver support and overall ability to come to a center that specializes in this.
Katherine Banwell:
What’s the process for accessing the CAR T?
Dr. Adriana Rossi:
The first important part is remembering they exist and having the referring physician remember to send patients our way. Once patients come to our center, they will meet with coordinators, both the clinic coordinators to make sure we have all of the testing, to make sure the heart is healthy enough, the lungs are healthy enough. There’s no infections brewing.
Financial coordinators to take care of all of the organizing. If patients are coming from further than 30 minutes, setting them up for a place to stay in the city, transportation aid, all of those things. Once we decide to go ahead and have our collection date set, that sort of starts the actual process. Since most of our patients have had stem cell transplants before, there is that point of comparison. I think one of the most important things to remember is CAR T is not stem cells.
So, while they’re both the cellular therapies, the patient experience is vastly, vastly different. It starts with a collection, where in stem cells you need several days of injections and maybe several days of collection. T-cell collection is a one-day event. We get what we get and then we are going to manufacture them and we can grow them in a Petri dish. There is no minimum and there is no instigating injections to get them going.
Once they’re collected, the cells are then sent for manufacturing, which may take from four to eight weeks. During that time, patients usually receive what we call a bridging therapy, which is some kind of therapy to keep the myeloma at bay. Not to get rid of it but to keep it under control so that once the cells are ready the patient is also ready. Going into CAR T with growing myeloma can increase the side effects.
Katherine Banwell:
Go ahead.
Dr. Adriana Rossi:
I will give you just the final bit. Once the cells are ready, then we plan to give chemotherapy to get the patient’s T cells to not put up a fight. That’s called lymphodepletion. We infuse the cells and they’re now with us for two weeks in the hospital and usually two weeks after.
Katherine Banwell:
Okay. So, I was going to ask how long patients are in the hospital for the procedure. So, that explains that. So, it is about two weeks. What signifies that a patient is ready to be released and go home?
Dr. Adriana Rossi:
The reason patients are in the hospital is a very classic expected toxicity experience. So, they’re in the hospital for us to observe, watch. If it happens, which about 80 percent of the time there will be some toxicity for us to address – one that toxicity has resolved, they’re then okay to go home.
Katherine Banwell:
Okay. That is great advice. Thank you. Of course, we know that CAR T-cell therapy comes with some potential side effects. Let’s talk about some of those side effects and how they’re managed. You mentioned cytokine release syndrome earlier. Let’s start with that. What is it, exactly?
Dr. Adriana Rossi:
Yes. As I mentioned, cytokines are molecules that the cells of the immune system use to communicate with each other. With this therapy, we are asking the T cells that have been infused to expand, meaning make multiple copies of themselves, and sweep through the body looking for myeloma and basically picking a fight with them.
So, CRS is what happens when the T cells are too good at their job and they overachieve and then picking a little fight kind of make a big ruckus. The result is what we call inflammation, which the patient will experience usually as a fever.
But if it does not go – if it continues to go unchecked, that fever can be accompanied by low blood pressure because of these inflammatory markers, difficulty breathing or low oxygen levels. And all of these things are now vastly prevented. CRS is usually treated very quickly and doesn’t get to these higher grades, more complicated fields.
Katherine Banwell:
How is CRS managed?
Dr. Adriana Rossi:
We have a couple of very good antidotes. CRS by itself is not just a fever. Certainly, a fever in any patient who is undergoing these kinds of therapies, we will try to rule out any infections. But there are markers in the blood that we can follow. When the blood markers and the fever occur at the same time, we know that cytokines are driving that effect. If it seems to be driven by something we call IL-6, we use tocilizumab (Actemra). If it seems to be driven by IL-1, we use anakinra (Kineret). These are all drugs that are themselves monoclonal antibodies which then will shut down that overreaction and cool things down.
Katherine Banwell:
Okay. Another possible side effect is neurotoxicity. Would you define that term for us?
Dr. Adriana Rossi:
Yes. That one is harder to define because neurotoxicity in itself is very broad. We usually think of something called ICANS, which is the neurotoxicity associated with the effector cells. That specific neurotoxicity tends to happen in conjunction with CRS.
And while CRS probably occurs in about 85 percent of patients, the ICANS is usually in the order of 5 percent. So, much, much more rare. And the antidote for that, which most patients know, love, and hate, is steroids.
Katherine Banwell:
Ah, yes.
Dr. Adriana Rossi:
I should mention there are other parts of neurotoxicity which I think the most concerning is something that has been known as Parkinsonian symptoms. It’s really just movement disorder. These are exceedingly rare and so we haven’t had a chance to learn very much because there are so few patients who have had this complication. We have learned from the first six patients who had this how to avoid it. And so, I think it’s now even more rare and it really goes into patient selection, to making sure, as I mentioned, that the myeloma isn’t growing very much.
We monitor to see if the T cells grow too fast, if the CRS is of a high level. These are all predictors of delayed neurotoxicity.
Katherine Banwell:
What are the signs of neurotoxicity in a patient?
Dr. Adriana Rossi:
Very specifically, for the ICANS, we have tool called the ICE tool, which is a series of questions to test memory and attention and ability to write and understand and speak. So, most commonly, it would be an inability to speak properly or, if someone is writing a sentence, it’s really a very classic finding. It is no longer spread across the page.
These are not subtle findings. Part of, again, being in the hospital is to allow us to have this tool twice a day and look for these signs very early on, interfere with their development by giving the patients steroids – usually for a day or two – and resolving it.
Katherine Banwell:
So, that’s how neurotoxicity is managed, then.
Dr. Adriana Rossi:
Yes.
Katherine Banwell:
And is there a potential for long-term issues associated with neurotoxicity?
Dr. Adriana Rossi:
Certainly, there is always the potential. But the vast majority – again, the ICANS tend to be self-limited while the patient’s in the hospital, and that is why we’re watching during that window. The delayed neurotoxicities, in addition to these very rare movement disorders, we do see some cranial nerve palsies. The seventh cranial nerve, usually recognized as Bell’s palsy, has happened a few times. We really don’t understand the mechanism of what is driving it. It’s inflammation but why there, why that way. So, we tend to use acyclovir, which is the classic treatment for Bell’s palsy and steroids.
Katherine Banwell:
Dr. Rossi, a suppressed immune system is something that a patient undergoing CAR T-cell therapy should consider. What does it mean and what precautions should patients take?
Dr. Adriana Rossi:
That is such a good question and it is specifically true for patients who are receiving therapies that target BCMA, which both commercial CAR Ts at the moment target.
Because it is such an effective therapy at bringing down cells that express BCMA, your immune cells that make antibodies, one of the side effects is the immunoglobulins, which are the antibodies, are all very, very low. So, that is one level of immunosuppression.
The other is the chemotherapy that we use to quiet the T cells can also lower all the blood counts. So, red blood cells and platelets may be low as well and those are not involved with immunity and can be transfused. So, that is a supportive mechanism. For the immune therapies, we usually use IVIG, which is intravenous immunoglobulins to support the patient until they’re able to make their own.
We also protect them from viral infections with acyclovir or valacyclovir. Protect them from something called PJP pneumonia, which is a virus that specifically appears when you’re very immunosuppressed. Should their neutrophil count be low, that is another type of white blood cell – make sure they’re protected with antibiotics.
Katherine Banwell:
Is there a typical timeframe for the immune system function to return?
Dr. Adriana Rossi:
I would say a year is a good time but it’s a very unpredictable wave. So again, unlike stem cell transplant where you have a clear time where the cells are low, they recover, they stay recovered, we have noticed for some patients, they may have low blood counts just during the first month and then be recovered. Some will have no problems in the first month and it’s in the weeks to follow that suddenly either the reds, or the platelets, or the white count may need support.
And in very rare instances, out to a year, they’re still needing support, sometimes say a growth factor injection once a week.
Katherine Banwell:
So, how is it monitored over time?
Dr. Adriana Rossi:
We monitor all those different levels of the immune system. So, we check on the CBC, which is the very common blood counts. We also look at what is called a lymph panel to look at the different types of T cells and make sure that they are recovering. Those usually take about three to six months to recover. The white count, again usually by Day 30, but there are some cases of delayed recovery. And the immunoglobulins, which is the antibody level, we also monitor monthly.
Katherine Banwell:
What other side effects should patients who are considering CAR T-cell therapy be aware of?
Dr. Adriana Rossi:
Really, those are the big three. I would say others are very rare but the low blood counts is the one that lasts beyond the time in the hospital. And the rare neurotoxicities that are delayed.
Katherine Banwell:
When should patients mention any issues they’re experiencing to their healthcare team?
Dr. Adriana Rossi:
Always. That is a very, very, short answer. Please don’t ever think you are bothering the doctor. I hear that a lot. “Oh, I didn’t want to bother you.” It is never a bother. This is why we are here. So, anything that is happening that is out of the ordinary, please let your healthcare provider know. If it is not something that needs our attention or we don’t need to worry about, we will tell you.
Katherine Banwell:
Better safe than sorry.
Dr. Adriana Rossi:
Always.
Katherine Banwell:
And how does a care partner factor into the process? It seems having a good support system is essential.
Dr. Adriana Rossi:
It absolutely is. I think the entire journey of myeloma really is what I would consider a team sport. It is not something we go through alone. And the more members of the team you have the better. So, as your medical team, we always value the caregivers. For CAR T specifically, since there is this concern for infections and neurotoxicity, caregivers are really essential. They should be well informed, know what to look for, and be the ones to reach out to us if anything is concerning. Again, any symptoms out of the ordinary, any fever, and really be a part of communicating with the medical team.
Katherine Banwell:
Is there a period where patients are considered out of the woods from CAR T side effects?
Dr. Adriana Rossi:
Hard to say. Again, I like to emphasize that most patients by Day 30 or 60 are back to work, are feeling themselves, are recovered. Another contrast to stem cell transplants. It’s a much faster recovery. I have patients who within 30 days are eager to go back to work and don’t know what I was talking about or why I insist on seeing them so much.
But some patients, again, out to a year, may still be requiring visits for support in either the IVIG for the immunoglobins, growth factor support for their counts. So, there are outliers at both extremes. We follow the model of 100 days for recovery.
Katherine Banwell:
Do some patient types do better than others?
Dr. Adriana Rossi:
Well, always yes. And we are still endeavoring to figure out who they are and why that is. There are things that we don’t know, can’t predict. But things that we do recognize are again bringing patients whose myeloma is under good control.
So, instead of having a lot of disease or disease that is in a growth phase, we try to use the bridging therapy to optimize the patient, not only to improve the response, but also minimize the toxicities.
Katherine Banwell:
Does age have an impact at all?
Dr. Adriana Rossi:
Not as much. We actually have just finished an 88-year-old patient whose hospital course was remarkably unremarkable, as we would like. I think another difference from stem cells, it is not as rigorous. While each patient, I think, should be part of that decision and that conversation, reviewing what is now a growing number of options and see if it’s right for them as an individual. So, age is a consideration, but frailty will always be the more important.
Katherine Banwell:
Dr. Rossi, we discussed the process of accessing CAR T-cell therapy, which can be a big undertaking. How do you counsel patients who are considering this treatment option?
Dr. Adriana Rossi:
Mostly, I want to make sure that they are well-educated and understand as much as we do and as much as we can convey. I am fortunate to be part of a big multidisciplinary team so there is social workers, clinical coordinators, other specialists, dentists, cardiologists, to give all of the perspectives. I like to make sure that they know what it is and also that they know what it isn’t. So, it is not a stem cell transplant and it is not another line of therapy that you just sign up for and go into blindly.
So, making sure they’ve had all of their questions answered, and it’s not something they read on the Internet. They have spoken with one of the CAR T physicians, understand all of the steps of the process, and have questions to their very individual needs addressed.
Katherine Banwell:
If a patient is interested in possibly doing CAR T-cell therapy, what questions should they ask their healthcare team?
Dr. Adriana Rossi:
I think again making it personal to them. Does the team think they are a good candidate? Is this the right time? Because they may be a good candidate but not even need it at the moment. Or, again, there are things that we could do between now and the cells to optimize the success both in efficacy and toxicity.
Understanding what side effects are expected for that individual because, again, we can usually judge these will be more likely or less likely. And then, do I have a plan in place to find the right center and continue the care and the monitoring near home after that?
Katherine Banwell:
What are the alternatives if a patient decides CAR T is not right for them?
Dr. Adriana Rossi:
I would say as part of this newest revolution and fairly comparable in novelty and method of action would be the bispecific antibodies. So, these are molecules.
They are not cells. And they activate the patient’s own T cells and bring the T cells to the myeloma, causing very similar side effect profile and very similar effectiveness. The rates are a little bit lower but they are administered as mostly a subcutaneous injection that has to be dosed weekly or every other week. The contrast is it’s a continuous therapy, but it does allow us to adjust as we go, which the cellular therapy doesn’t.
Katherine Banwell:
While there are approved CAR T-cell therapies for myeloma currently, there are also many others that are in clinical trials. Would you talk about some of the ongoing research in this area?
Dr. Adriana Rossi:
Absolutely. Again, while we celebrate the tremendous changes that these two CAR Ts have made to the field, they are both autologous, meaning we use the patient’s own T cells for manufacturing. They both target BCMA. And they are both what we call second generation T cells. So, other areas are to change the target. So, instead of just targeting BCMA, there are studies specifically targeting GPRC5D, which are coming down fairly soon. Rather than using the patient’s own T cells there are a number of products that use a healthy donor’s T cells, which are available immediately.
So, we don’t need to go through the bridging therapy, and we don’t have to wait for the cells to be ready. And lastly, there are different manufacturing processes. As I mentioned, the ones we currently have may take up to eight weeks for manufacturing. There are some studies now where cells are basically manufactured, engineered, in 48 hours –
Katherine Banwell:
Oh, wow.
Dr. Adriana Rossi:
– and are ready to be infused so that they actually grow in the patient rather than in a Petri dish. So, lots of areas of exploration and I look forward to, in five years, being able to look back and see again how the field has changed.
Katherine Banwell:
And I’m sure it will, by the sounds of it. Are there any trials introducing CAR T-cell therapy as an earlier line of myeloma treatment?
Dr. Adriana Rossi:
There are. So, both the products that are now commercially available for the fourth line are being studied in earlier and earlier lines. We actually just this year got results of the CARTITUDE-4 study, which was in one to three prior lines, and expect that that will lead to an earlier approval in the very near future.
And we have a number of studies, again, with both products looking at patients who have either high risk disease or don’t respond as well as we would like to their frontline therapy, and actually being used as part of that first line.
Katherine Banwell:
Dr. Rossi, what advice do you have for patients who may be hesitant to participate in a clinical trial?
Dr. Adriana Rossi:
Education. More than anything, understand what they are. Clinical trials come in all shapes and sizes. We have these exciting molecules that have to go into a first human at some point but we also have tried and true therapies that we know – for example, the CAR T – that is approved in these later lines. That same product is being now offered earlier. So, that has to be within a clinical trial because it’s not the approved indication.
But it is a product that we know to be safe. We know that it works in advanced disease and are actually expecting that it will work even better in earlier lines. So, clinical trials is a very broad term. Understanding what the patient may be eligible for – meaning, what the study’s looking for – and then comparing that to what the patient is looking for. So, sometimes it’s even modes of therapy. So, if you’re specifically looking for an oral agent, there may be studies that don’t require injections or that many visits. So, really looking widely, speaking to your healthcare physician, and understanding what the options are.
Katherine Banwell:
And if a patient is interested in possibly participating in a clinical trial, what sorts of questions should they ask?
Dr. Adriana Rossi:
Very, very good question. First, understanding what clinical trial. Each center will have their own combination. Some studies are available in multiple locations. Some studies are very institution specific. So, meeting with the research team and understanding what are the required testings, what is the required treatments, and what is the required follow-up, I think, is the first part.
Clinical trials, in order for them to give us the power to generalize and learn lessons are very strict in trying to keep to the schedule just as specified and everything is much more contained. So, making sure that they again understand what they’re signing up for and what they’ll get out of it.
Katherine Banwell:
What other myeloma research are you excited about?
Dr. Adriana Rossi:
Well, my focus is in CAR T and so I think, with bias, that is the most exciting part. But I did mention bispecifics. One of the things we need to concede is CAR T really requires you be at a cellular therapy center.
Whereas, with the bispecifics, while for now experience is still building, the idea is that this is something that could be administered in any practice across the nation. So, being able to reach more patients and those also with different targets, different schedules, different combinations, was another very interesting field as well.
Katherine Banwell:
As we close out this conversation, Dr. Rossi, I would like to get your take on the future of myeloma. What makes you hopeful?
Dr. Adriana Rossi:
Just looking back, I think. Again, in the 20 years that I’ve been fortunate enough to participate and see the changes, we have gone through, as I mentioned, three of the four revolutions in the field. And the speed with which each step forward then begets three or four more. As I mentioned, in five years I think we’ll look back and say, “Oh, how quaint, what we were doing in 2023.” So, the speed and the number of wins we’re getting and how quickly that’s translating into direct patient experience is really incredible.
Katherine Banwell:
Yeah. It seems like there’s a lot of progress and hope in the field.
Dr. Adriana Rossi:
There absolutely is.
Katherine Banwell:
Well, Dr. Rossi, thank you so much for taking the time to join us today.
Dr. Adriana Rossi:
Absolutely. It’s been my pleasure.
Katherine Banwell:
And thank you to all of our collaborators. To learn more about myeloma and to access tools to help you become a proactive patient, visit powerfulpatients.org. I’m Katherine Banwell. Thanks for being with us today.
What Non-Small Cell Lung Cancer Treatment is Right for You?
/in INSIST! Lung Cancer, LC Insist Treatment, LC Newly Diagnosed, LC Programs, LC Testing, LC Videos ND, LC Videos T, Lung Cancer /by Kara RayburnWhat Non-Small Cell Lung Cancer Treatment is Right for You? from Patient Empowerment Network on Vimeo.
What’s the best approach for YOUR lung cancer? Dr. Isabel Preeshagul discusses the importance of engaging in your lung cancer care decisions, shares advice for working with your team to determine a treatment approach, and reviews factors that affect therapy options. Dr. Preeshagul also provides an update on the latest research and clinical trials.
Dr. Isabel Preeshagul is a thoracic medical oncologist at Memorial Sloan Kettering Cancer Center. Learn more about Dr. Preeshagul.
Download Program Resource Guide
See More From INSIST! Lung Cancer
Related Resources:
An Expert Explains Predictive Biomarker Testing for Lung Cancer
Personalized Lung Cancer Treatment | Key Factors to Consider
Understanding Currently Available Non-Small Cell Lung Cancer Treatments
Transcript:
Katherine Banwell:
Hello and welcome. I’m Katherine Banwell, your host for today’s program. Today, we’ll discuss the latest advances in non-small cell lung cancer care as part of our Insist series, which encourages patients to play an active role and insist on better care. Before we get into the discussion, please remember that this program is not a substitute for seeking medical advice. Please refer to your healthcare team about what might be best for you. Well, let’s meet our guest today. Joining me is Dr. Isabel Preeshagul. Dr. Preeshagul, it’s so good to have you with us. Thank you. Would you introduce yourself?
Dr. Isabel Preeshagul:
Yes. Thank you so much for having me and for the very kind introduction. My name’s Isabel Preeshagul. I am a Thoracic Medical Oncologist at Memorial Sloan Kettering Cancer Center, and it is a huge honor to be here with you today.
Katherine Banwell:
Well, we’re so glad to have you with us. I’d like to start with a question pertaining to our series title, Insist. Why is it essential for patients to collaborate with their providers on care treatment decisions?
Dr. Isabel Preeshagul:
So, collaborating is so important, right? I always tell my patients this is not a dictatorship, right? This is a collaborative effort where I’m here to guide you, but you are the captain of the ship.
You are the one that needs to make all of the decisions, and I’m here to make sure that the ship goes in a smooth direction, so making sure we have open lines of communication that the patients and their caregivers feel comfortable talking to me and my team and also vice versa and that we trust each other. It’s so important because we are going for a marathon, right? We’re not going for a sprint. This is a long-term relationship, whether we’re treating for cure or we’re treating you with palliative intent and it’s treatable but not curable. We’re going to be following with each other for a long time.
Katherine Banwell:
A lung cancer healthcare team, of course, consists of a number of different providers. Would you tell us about the various members on a team?
Dr. Isabel Preeshagul:
Sure. So, there is – there are the people that do the scheduling, that make sure that the CAT scan is scheduled, that the MRI is done, your chemo gets scheduled, all of that. The schedulers are super important and an integral part of our team.
And then we also have our office coordinators that answers the phone calls and passes along the messages and assists with scheduling and sort of sets expectations and is the face of the practice. Then you have an office practice nurse or an oncology practice nurse who is the doctor’s right hand, making sure that the patients get proper chemotherapy teaches, making sure that they understand about possible side effects, risks versus benefits, making sure medications are up to date, assessing symptoms.
They are sort of the front line when it comes to any patient call they’re triaging, and they’re escalating or deescalating. That would be the office practice nurse. And then you have an advanced care practitioner, an APP. You either have a nurse practitioner or a PA that’s working with you that’s sometimes seeing patients independently, sometimes putting chemotherapy orders, you know, really serving as almost as another doctor.
If for some reason there is something that the doctor’s not available to do, the doctor needs in a pinch, or my patients that are almost at long-term follow-up that are doing great that are just kind of coasting, I will share with my NP and make sure that they know her just as well as they know me. And sometimes there’s a fellow or there’s a resident or there’s a med student that’s part of the team as well because see one, do one, teach one. It’s really important to teach those that are coming after you and serve as mentors and really include them in part of the team and part of the decision-making. And then you have the doctor that just kind of oversees everything.
Katherine Banwell:
Of course. How would you define treatment goals for people with lung cancer?
Dr. Isabel Preeshagul:
So, the goal of treatment, I think, is really contingent upon someone’s stage, but it’s also contingent upon what’s important to the patient, right? So, we have patients that are stage I all the way to stage IIIC that we treat with intention to cure.
And patients that have stage IV disease, it’s treatable but not curable. So, I am very transparent with that as long as I have the information to have that discussion. With that being said, there are some patients with stage IIIdisease or stage I disease that don’t really want treatment and want to focus on quality of life. And that’s okay too. And in which case, you know, at some point, their cancer will likely progress. How quickly or when that will happen, we don’t know. Could they pass from something else? It’s possible. But you really need to talk about what’s important to the patient, because it’s not always cut and dry.
Katherine Banwell:
As you mentioned, Dr. Preeshagul, there are several different support members on a team. What would you say to patients or even care partners who can sometimes feel like they’re bothering their healthcare team with their questions and comments?
Dr. Isabel Preeshagul:
So, we do get that concern a lot. And I always say, “I’m here for you 24/7. And, if it’s not me, it’s someone that’s just as qualified to answer your questions no matter what.”
“And I would rather get a phone call at 3:00 a.m. than get a phone call at 9:00 a.m., and you need to go to the hospital right now or God forbid something happened. I get a phone call from someone in the ICU that you went overnight and terrible things happened. So, I want the phone calls to come through to keep you out of the hospital and keep you from going south. So, call me.” And I never try to – I don’t try to outline contingency plans or criteria of what would warrant a call, because then you end up getting in trouble.
I always just tell my patient, “Think about how you’re feeling now in front of me. If you’re feeling any different than how you feel at this very moment, call me.”
Katherine Banwell:
Good advice. I’d like to turn to the clinical side of non-small cell lung cancer. What tests help you identify the type and stage of lung cancer?
Dr. Isabel Preeshagul:
Obviously, you need a CAT scan. You need a CAT scan of the chest, abdomen, pelvis, and you need an MRI brain and a PET scan.
Those are really the gold standards for determining clinical staging. In regards to pathologic staging, it’s really important to have tissue samplings. So, you biopsy a site of disease that’s concerning to you. If it looks like there’s only disease in the chest, you want to biopsy the site where there’s the tumor, and then you talk with your thoracic surgery or pulmonary team to determine the best way to sample the mediastinum for full staging.
Katherine Banwell:
Why is an accurate diagnosis so important?
Dr. Isabel Preeshagul:
So, an accurate diagnosis is so important because lung cancer is by no means black and white anymore. There are so many histologic subtypes that we are learning about. There are so many different molecular drivers that we are learning about. So, making sure you have the right diagnosis, full and next-generation sequencing testing, all of the imaging that you need could really make or break your treatment plan.
Katherine Banwell:
Dr. Preeshagul, let’s talk about biomarker testing. How is biomarker testing for lung cancer different from hereditary genetic testing?
Dr. Isabel Preeshagul:
So, we do do hereditary genetic testing for lung cancer patients as well. So, I think let’s backtrack a little bit. When you’re doing on a patient, there’s germline mutations and there’s somatic mutations. And germline mutations are mutations that you might get from Mom and Dad that they got from their parents and so on and so forth that you could give to your children or your brother and sister or whatever. So, that’s germline testing that could be passed along.
That would be like BRCA or any other APC gene, but we are learning more and more that there are mutations in lung cancer that do have a hereditary aspect to them. So, we are learning now that while we do somatic testing, which is to find a mutation that just spontaneously happened in your tumor all on its own, it’s really important to pair that with germline testing to make sure that there isn’t some kind of heritable mutation that’s also driving this lung cancer.
Katherine Banwell:
You mentioned hereditary genetic testing. Should family members of people with lung cancer undergo genetic testing then just to be reassured?
Dr. Isabel Preeshagul:
So, if there is a germline mutation, then they should – the family members should be referred to a geneticist to have that discussion.
Katherine Banwell:
What are common lung cancer biomarkers?
Dr. Isabel Preeshagul:
So, we have nine biomarkers within approval right now, but there are so many. There’s more than I could even talk about today. But some of the more common ones are EGFR, ALK, ROS1, MET exon 14. You have KRAS, KRAS-G12C, which is a newer one. We have NTRK. We have RET. The list goes on, HER2. I could talk for – there’s not enough time on this Zoom video to talk about all of the mutations. But there are nine mutations with approvals as of now to date, this very moment. That could change tomorrow.
Katherine Banwell:
Of course, it could. How do biomarkers in lung cancer affect treatment options for lung cancer patients?
Dr. Isabel Preeshagul:
So, it used to only be in stage IV, but now we are learning that biomarker testing is really important from the get-go because we have induction or neoadjuvant protocols that are looking at giving targeted therapy before patients go to surgery.
We know that there’s FDA approval for patients to get targeted therapy after surgery, and there’s a survival advantage there. So, make sure that you have next-generation sequencing testing regardless of your stage.
Katherine Banwell:
Okay. That’s good advice. So, we’ve heard how testing and a patient’s individual disease can lead to more targeted options. And you just mentioned targeted therapies. How do they work?
Dr. Isabel Preeshagul:
So, there’s many different targeted therapies that we have. Some of given as an infusion. For HER2, for example, we have TDXD, and we have T-DM1. TDXD is the only drug that’s FDA-approved in this setting. There are clinical trials looking at T-DM1. For EGFR Exon 20, we have another infusional drug called amivantamab (Rybrevant). For EGFR Exon 19 and Exon 21, we have a pill called osimertinib (Tagrisso). For KRAS, there’s a pill. For most of the driver alterations, it’s a pill, but some of them it does require infusional therapy.
But these are therapies that are targeted at the cells that harbor that mutation.
Katherine Banwell:
Let’s turn to immunotherapy. What is it, and how does it work?
Dr. Isabel Preeshagul:
So, immunotherapy is basically teaching your body to recognize cancer as foreign. So, when you have – I always kind of use this hand model. So, basically, a normal cell has, let’s say, three prongs. And then sometimes what happens is cancer will grow a marker called PD-L1 that makes it hide from the immune system. So, the body thinks that this is a normal cell. So, what immunotherapy does is it comes up and it sort of puts a cap on that PD-L1 so that the cell looks foreign again and the body can attack that cell and get rid of it. So, it’s almost like ramping up your immune system to recognize that marker and get rid of that cell.
Katherine Banwell:
What is the regimen for immunotherapy, and how often is treatment administered?
Dr. Isabel Preeshagul:
So, immunotherapy is approved in the neoadjuvant setting, which means before chemotherapy. It’s approved after chemotherapy, and it’s approved in the stage IV setting. There are many different regimens and many different dosings and many different drugs. But it’s typically given in your veins, either once every three weeks or once every four weeks for a certain amount of time. If it’s given in a curative setting and it’s given indefinitely or until there’s disease progression or intolerance in the stage IV setting.
Katherine Banwell:
Okay. Let’s touch upon the side effects of these types of treatment. You’ve mentioned that there are so many, but what are some of the major side effects, and how are they managed?
Dr. Isabel Preeshagul:
Side effects of immunotherapy can include pneumonitis, which is inflammation of the lungs, any kind of endocrinopathy like issues with your thyroid, issues with your pancreas like diabetes.
It can cause colitis, which is diarrhea, inflammation of the colon, hepatitis, inflammation of the liver. It can cause cerebritis, inflammation of the brain. It can cause arthritis or arthralgias, inflammation of the bones. And it can also cause rash and fatigue.
Typically, if it’s the thyroid, it’s managed with thyroid replacement hormone or a drug that would calm down the thyroid if it’s overactive. Pneumonitis is steroids. Hepatitis is sometimes treated with steroids. Colitis, steroids typically. Steroids usually come somewhere in there, usually not with the endocrinopathies, but the other itis’s, it’s typically – we start with steroids and go up from there. And the goal is to really recognize these toxicities before they become a problem and just at the glimmer of them just starting.
Katherine Banwell:
So, would you consider these treatments to be personalized medicine then?
Dr. Isabel Preeshagul:
So, it’s personalized in the sense that if someone has a high PD-L1 expression, there may be some data to demonstrate that they may benefit from immunotherapy or have a response. If someone can’t tolerate chemotherapy or is not interested in chemotherapy or has other reasons that may preclude them from getting it, it might be reasonable. So, in that sense, it is considered personalized.
Katherine Banwell:
How would you define personalized medicine?
Dr. Isabel Preeshagul:
To me, personalized medicine takes into account the biologic makeup of a patient’s disease like if they have a mutation and what their PD-L1 status is, what the histologic makeup of it. What’s their stage? And then, on the other hand, what’s important to that patient? If they’re a tailor, you want to make sure you’re not giving them a medication that’s going to cause neuropathy, so they can’t use their hands.
If they enjoy playing the harp or the piano, same thing. If their goal is to continue to run marathons, you may want to avoid something that’s going to cause inflammation of the lungs and risk them for pneumonitis. Tailoring to make sure that the treatment is part of their life but does not become their life.
Katherine Banwell:
If the test results don’t reveal one of the biomarkers you’ve been talking about, what other treatments are available?
Dr. Isabel Preeshagul:
So, if I don’t have an FDA approval, then sometimes we look to see if there is a clinical trial in our early phase drug development program, and we talk about a clinical trial. If there’s no clinical trial and I don’t have an FDA approval, then we have to talk about what options are considered standard of care and how to make that work into the patient’s lifestyle.
Katherine Banwell:
What about surgery? When is it used?
Dr. Isabel Preeshagul:
Surgery is typically used in the curative setting with early-stage disease. We’re really trying to give patients some kind of chemotherapy or some kind of treatment before they go to surgery. It’s shown to improve outcomes. It just gives us a en vivo view of how the tumor will respond to the treatment. So, we typically use surgery in the curative setting. And, at times, it’s appropriate to use surgery for a metastasectomy when you have one little site that’s growing. Sometimes after a tumor board discussion, it might be reasonable to resect that area.
Katherine Banwell:
Is radiation still used?
Dr. Isabel Preeshagul:
Same thing. It can be used in the curative setting, typically for patients with stage IIIB or stage IIIC disease and combined with chemotherapy patients that are not considered surgical candidates, or it’s used in the palliative setting when patients have painful metastases.
Katherine Banwell:
Would you define the B and C? You’ve mentioned that a couple of times.
Dr. Isabel Preeshagul:
Yeah.
Katherine Banwell:
We’re used to hearing Stage 1, 2, 3, 4. But what’s a stage IIIB and a stage IIIC?
Dr. Isabel Preeshagul:
Yeah. Sure. Sure. So, it does get a little bit into the weeds here about the size of the tumor and the amount of lymph nodes and location of the lymph nodes. But basically, stage IIIA is considered resectable. That means – that could be the size of the tumor with no lymph nodes, or it could be a smaller tumor with a lymph node on the same side as the disease. Stage IIIB would be a lymph node right underneath the windpipe at the station 7. And stage IIIB also includes lymph nodes that have crossed over to the contralateral side. And stage IIIC would be lymph nodes that are maybe up at the contralateral supraclavicular space.
Katherine Banwell:
Okay. Do treatment options change if the lung cancer returns?
Dr. Isabel Preeshagul:
Yes, they do change depending on if this is the same tumor type that’s come back. It’s typically a different treatment algorithm, yeah.
Katherine Banwell:
Okay. And should biomarker testing be done again if a relapse occurs?
Dr. Isabel Preeshagul:
100 percent. Because it guides everything about a patient’s treatment. It’s super important.
Katherine Banwell:
Okay. What are you excited about right now in lung cancer research?
Dr. Isabel Preeshagul:
I am excited and overwhelmed by the fact that we have so many approvals and so much exciting data that was just presented at ASCO and World Lung and ESMO that it’s next to impossible to keep up. And I’m happy that we have that problem, and I’m happy that the patients have – there’s a spotlight on lung cancer when we were in the shadows. And now, I think we have the spotlight.
And all of these approvals, you know, with it being Lung Cancer Awareness Month as well, I think is just so important. Just to make sure that we get the knowledge of these new approvals out there though, that is another struggle.
Katherine Banwell:
Well, are there any current clinical trials that look promising to you?
Dr. Isabel Preeshagul:
Yeah, I think there are many clinical trials. In the induction setting, there was some data that was just presented on ALINA looking at adjuvant alectinib (Alecensa). We just had a – we have approval for adjuvant osimertinib (Tagrisso) and the ADAURA trial.
But we are learning more and more that as these targeted therapies have approval in stage IV, we’re trialing them in stage III, and then we’re going to trial them in earlier stages and earlier settings. So, this has been the pattern of how drugs get approved. So, yes, there’s lots of exciting data coming through.
Katherine Banwell:
That’s excellent. Can you talk about antibody drug conjugates and where they fit into lung cancer care?
Dr. Isabel Preeshagul:
Yeah. That’s a great question. I don’t think anyone knows the answer as to where they fit in just yet.
We have probably over 300 antibody drug conjugates that are in development right now. And one of the more common ones that we use is trastuzumab deruxtecan (Enhertu), or TDXD, which is used in patients that harbor HER2 alterations in the stage IV lung cancer setting. It is basically almost like a Trojan horse. So, you have this antibody.
It’s typically IgG1, immunoglobulin. And then you have a linker, and then at the end of that linker is the warhead or the chemotherapy agent. So, the antibody comes in towards the cancer cell looking very innocent. It binds to the cancer cell. And, once it binds, then everyone inside the Trojan horse or this warhead rush into the cell and get to do its damage. So, it’s a totally different mechanism. We’re trying to outsmart some of the bypass mechanisms that cancer cells develop. And this may be the new wave, but stay tuned, more to come.
Katherine Banwell:
Right. So, it’s promising. How can patients find out more about current clinical trials?
Dr. Isabel Preeshagul:
So, you can always ask your healthcare practitioner if there are any clinical trials at the institution that you’re at, but clinicaltrials.gov has all the clinical trials that are available nationally and internationally.
You just type in your disease type. You can type in a couple keywords, EGFR maybe or ROS1 or stage IV, something along those lines, and then it should populate a list of clinical trials and what institutions have them open, if they’re still accruing or if they’re not, and a contact on that trial.
Katherine Banwell:
If a patient is interested in a clinical trial, what kinds of questions should they be asking their healthcare about the trial?
Dr. Isabel Preeshagul:
So, the first question to ask is, “Do we have any clinical trials that are appropriate for me?” If the answer is yes, “Are they appropriate for me now, or are they appropriate for me if what I’m on right now is not working?”
So, trying to figure out where that will be, and if they are appropriate for you now, how can I get evaluated, and how can we get things underway?
Katherine Banwell:
Yeah. What would you say to patients who are interested in participating in a clinical trial, but they’re nervous about it?
Dr. Isabel Preeshagul:
I think one thing that I love about being on a clinical trial is that there are more eyes are on you, because we are looking to get something approved, and we are just watching every single little granular detail. In a way, it’s almost like you’re being more micromanaged than if you were on standard of care because of just how many stops and checks there are, how many eyes are looking at your labs after the doctor and the nurse and the nurse practitioner, and the fellow take a look at everything. It’s 10 other people. So, it’s almost like it’s extra safe because of all of that. It’s exciting because you are hopefully getting tomorrow’s treatment today, right?
You’re trailblazing the way for other people after you. So, I think it’s exciting, but, of course, it’s nerve-wracking. It’s something new. You don’t know if it’s going to work. But I have to believe that the way that clinical trials are designed now and the clinical trials that we choose to open here, we really hope are going to be pushing the space forward.
Katherine Banwell:
Yeah. I’d like to get to a few questions that we received from audience members prior to the program. How do you help a family member that is an overwhelmed caregiver but refuses help? Any tips on how to provide support to this person?
Dr. Isabel Preeshagul:
I mean, I think we see caregiver burnout thousands of times a day, unfortunately, and the first thing is knowing how to recognize it. And the second most important thing is taking the time away from the visit with the patient to address the burnt-out caregiver, because there is not enough time in any visit to ever – there’s never enough time in my mind to spend with a patient.
I’m always pulled in a thousand different directions. And I think we all feel that. But taking the appropriate time to sit down and to say, “Hey. Listen. I recognize that you’re burnt out. I can see it. Who is in your corner helping you?” And just directing focus away from the patient just for a moment and to really focus on that caregiver and to rely on the social work team and the case manager and the support groups that your institution may have and to make sure that they know about those resources.
Katherine Banwell:
Yeah. Here’s another question we received. “Can you share more information regarding treatments available for stage IV lung cancer and their side effects?”
Dr. Isabel Preeshagul:
It depends on if this is non-small cell or small cell. It depends on if you have a driver alteration or not. So, I think that is a little bit challenging to talk about in just one session. But basically, you’re probably looking at some kind of targeted therapy if you have a mutation versus standard of care if you don’t have a targeted mutation versus a clinical trial. And I think those are kind of like the big baskets.
Katherine Banwell:
When is a second opinion necessary? Dr. Isabel Preeshagul: A second opinion is necessary anytime you want a second opinion.
Dr. Isabel Preeshagul:
There is no right or wrong time, any time. You’re just not jiving with your oncologist after the first day you met them, second opinion. You’re at the end of the line and you really want toknow more, second opinion. You’ve met two other doctors. You’re not jiving, third opinion. It’s always appropriate anytime you want.
Katherine Banwell:
So, the patient shouldn’t feel obligated to stay with that one provider?
Dr. Isabel Preeshagul:
Never. Never, never, never, never, never. No. Please don’t feel that way. There are no hard feelings. And, if there are, that’s not the right oncologist for you. It needs to feel like a perfect friendship. And, if it’s not that, it’s not the right thing.
Katherine Banwell:
Before we close, Dr. Preeshagul, I’d like to get your final thoughts. What would you say to the audience about the future of lung cancer care and treatment?
Dr. Isabel Preeshagul:
I do think that the future is bright because, as I mentioned, there is now this light that is shining in the lung cancer space. And things are getting approved. and discoveries are getting made faster than we can even keep up, which is exciting and overwhelming and daunting. But I am happy that, finally, this space is taking off, so I feel optimistic.
Katherine Banwell:
Okay. All right. Well, I wanna thank you so much for taking the time to join us today, Dr. Preeshagul.
Dr. Isabel Preeshagul:
Thank you so much for having me. These were wonderful questions, and I look forward to many more discussions with you. Thank you.
Katherine Banwell:
And thank you to all of our partners. To learn more about lung cancer and to access tools to help you become a proactive patient, visit powerfulpatients.org. I’m Katherine Banwell. Thanks for being with us today.