Tag Archive for: Multiple Myeloma treatment

Understanding CAR T-Cell Therapy | How It Works and Who It’s Right For

/in , , , , , , , /by

Understanding CAR T-Cell Therapy | How It Works and Who It’s Right For from Patient Empowerment Network on Vimeo.

How is CAR T-cell therapy changing myeloma care? Dr. Adriana Rossi explains how CAR T-cell therapy works to fight myeloma and which patient type is most appropriate for this treatment option.

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.

See More From Thrive CAR T-Cell Therapy

Related Resources:

Questions to Ask Your Doctor About CAR T-Cell Therapy

Questions to Ask Your Doctor About CAR T-Cell Therapy

 What You Need to Know About Accessing CAR T-Cell Therapy

What You Need to Know About Accessing CAR T-Cell Therapy

 Myeloma Research | CAR T-Cell Therapy Clinical Trials

Myeloma Research | CAR T-Cell Therapy Clinical Trials

Transcript:

Katherine Banwell:

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.  

Thrive | Advice for Managing Potential CAR T-Cell Therapy Side Effects

/in , , , , , , , /by

Thrive | Advice for Managing Potential CAR T-Cell Therapy Side Effects from Patient Empowerment Network on Vimeo.

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.

Download Resource Guide

See More From Thrive CAR T-Cell Therapy

Related Resources:

Considering CAR T-Cell Therapy for Myeloma_ Key Questions to Ask Your Doctor

Considering CAR T-Cell Therapy for Myeloma? Key Questions to Ask Your Doctor 

 Advice for Myeloma Patients Undergoing CAR T-Cell Therapy

Advice for Myeloma Patients Undergoing CAR T-Cell Therapy 

 Questions to Ask Your Doctor About CAR T-Cell Therapy

Questions to Ask Your Doctor About 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.   

Questions to Ask Your Doctor About CAR T-Cell Therapy

/in , , , , , , , /by

Questions to Ask Your Doctor About CAR T-Cell Therapy from Patient Empowerment Network on Vimeo.

What should you know when considering CAR T-cell therapy for myeloma? This animated explainer video provides an overview of key questions to ask your healthcare team and advice for patients and care partners when considering CAR T-cell therapy.

See More from Evolve Myeloma

Related Resources:

Considering CAR T-Cell Therapy for Myeloma_ Key Questions to Ask Your Doctor

 Accessing Myeloma CAR T-Cell Therapy Clinical Trials

Accessing Myeloma CAR T-Cell Therapy Clinical Trials

Transcript:

While receiving a myeloma diagnosis and choosing a therapy can be overwhelming, advancements in research are providing more options and more hope for patients than ever.  

And these advancements include CAR T-cell therapy – a treatment in which a patient’s T cells, a type of immune system cell, are laboratory-altered to attack cancer cells in the body.  

If you are curious about this option, consider asking your healthcare team these key questions: 

  • Am I a candidate? 

CAR T-cell therapy patients must meet specific criteria. 

  • What are the risks? Common side effects of this type of therapy are cytokine release syndrome (CRS), neurotoxicity, suppressed immune system, and low blood counts. 
  • Is the timing right for me? The current approval is for patients who are later in their myeloma journey. 
  • Are there alternatives? Ask about other treatment options that may be appropriate for your myeloma. 
  • Is there a clinical trial that may be right for me? There are many myeloma treatments available in clinical trials, there may even be CAR T-cell therapy options. 
  • What is the cost? Every person’s insurance situation is different so it’s important to understand what the financial impact will be. 
  • What is the center’s experience with CAR T-cell therapy? Your healthcare team should be well-versed in this type of treatment. 

Beyond asking these questions, it’s also critical to research the therapy on your own –– ask your doctor where to find reliable information about the options you are considering.   

You should also discuss the pros and cons of each treatment option with your healthcare team, inquiring about potential side effects, and understand how the treatment is administered and the frequency of appointments. 

And it’s always a good idea to review your treatment choices with a care partner, such as a friend or loved one – someone you trust. 

Finally, always speak up and ask questions. Remember, you have a voice in YOUR myeloma care. 

To learn more about myeloma and to access tools for self-advocacy, visit powerfulpatients.org/myeloma.  

Evolve Myeloma Resource Guide

/in , , , , , , , /by

Download Resource Guide

PEN-181_EvolveMMResourceGuide_F

Download Resource Guide

See More from Evolve Myeloma

Advances in Myeloma Treatment | CAR T-Cell Therapy and Bispecific Antibodies

/in , , , , , , , /by

Advances in Myeloma Treatment | CAR T-Cell Therapy and Bispecific Antibodies from Patient Empowerment Network on Vimeo.

How are new treatments impacting the landscape of myeloma care? Dr. Francesca Cottini explains the role of bispecific antibody therapy and CAR T-cell therapy and how these emerging therapies are changing myeloma care.

Dr. Francesca Cottini is Assistant Professor in the Division of Hematology at the Ohio State University Comprehensive Cancer Center. Learn more about Dr. Cottini.

Download Resource Guide

See More From INSIST! Myeloma

Related Programs:

How Close Is Personalized Medicine for Myeloma?

How Close Is Personalized Medicine for Myeloma?

How Do Myeloma Test Results Influence Prognosis and Care?

How Do Myeloma Test Results Influence Prognosis and Care?

 Making Treatment Decisions: Understanding Common Myeloma Therapies

Making Treatment Decisions | Understanding Common Myeloma Therapies

Transcript:

Katherine:

Dr. Cottini, I’m wondering if you could briefly go over CAR T-cell therapy and bispecific antibodies. 

Dr. Cottini:

Yes, of course. So, these are all our new therapeutic approaches for patients. And these are types of treatments that are given to patients that already went through their induction, they went into remission, maybe they had a bone marrow transplant.  

And then, after a couple of years or months, unfortunately, the disease came back, and they need the new and different treatment options. So, these two strategies, CAR T and bispecific antibodies, really rely on the T-cells, on the immune cells of the patient. 

And they all focus and target a specific marker on the plasma cells, but they work a little bit differently. So, the bispecific antibodies – and we have different antibodies.  

Some are approved by the FDA, some are just in clinical trials. They practically recognize something that is on the plasma cells, on the myeloma cells, that can be BCMA, GPRC5D, or other targets. So, at the same time that I am able to get close by the T cells, the immune cells, and in this way, practically there is both the antibodies and also the immune cells which is activating and getting rid of the cancer cells. 

So, these are infusions. Often, they’re done initially in the hospital and then in the outpatient setting. Sometimes it’s even every week, every other week or so.  

CAR T are different strategies, and it’s a very smart way of trying to get rid of the cancer cells. So, practically, these are T cells.  

So, these are immune cells from you, from the patient. And they are practically taken and then brought to a very specific and clean facilities where these T cells are modified in order to be able to recognize the cancer cells. 

And then these cancer cells are sent back to us, and then practically they are given into the veins to patient, and then there is this kind of reaction of these T cells, which are very peppy and aggressive to be able to kill all the remaining cancer cells. So, these are all the new strategies. 

Obviously, we are kind of like in the early process, but these are very promising therapies I think we’ll be maybe moved up front even with diagnosis in the next 10, 20 years, we don’t know.  

Making Treatment Decisions | Understanding Common Myeloma Therapies

/in , , , , , , , /by

Making Treatment Decisions | Understanding Common Myeloma Therapies from Patient Empowerment Network on Vimeo.

What are common myeloma therapies, and when are they used? Dr. Ashley Rosko outlines the factors that impact treatment decisions and reviews available therapies including stem cell transplant, proteasome inhibitors, immunomodulatory therapies, and monoclonal antibodies.

Dr. Ashley Rosko is Medical Director of the Oncogeriatric Program at the Ohio State University Comprehensive Cancer Center – The James. Learn more about Dr. Rosko.

Download Resource Guide

See More From INSIST! Myeloma

Related Programs:

How Close Is Personalized Medicine for Myeloma?

How Close Is Personalized Medicine for Myeloma?

How Do Myeloma Test Results Influence Prognosis and Care?

How Do Myeloma Test Results Influence Prognosis and Care?

 Advances in Myeloma Treatment: CAR T-Cell Therapy and Bispecific Antibodies

Advances in Myeloma Treatment | CAR T-Cell Therapy and Bispecific Antibodies

Transcript:

Katherine:

We know that multiple myeloma patients have a number of options and that many available therapies are used in combination. 

So, I’d like you to walk us through the options that are available. 

Dr. Rosko:

So, I’m going to start by how the best way that I can frame out when we talk about newly diagnosed versus patients when they have relapse. So, there are therapies that are available for patients that are FDA-approved when they are newly diagnosed with the cancer, and there are therapies that are approved only when a cancer has acted up again or relapsed. 

So, I’ll kind of frame it from patients who are newly diagnosed. And then, I also will talk more about relapsed therapies and what we’re able to offer to patients. So, in first, when we talk about treatment options, we frame treatment based on a couple things. So, one is, we talk extensively about the disease biology. So, that plays an important role in how we decide which treatment the patient should get. 

And then, the second part about how – I would probably say there’s about four main parts. And so, disease biology is one, and another thing has to do with the patient characteristics. In terms of the patient’s overall health prior to developing cancer, and also how the cancer has impacted their health in terms of everyday activities. Whether or not a person has really slowed down quickly, whether they’ve been in the hospital, and how it’s impacting their organs. Because that plays a role in terms of what we’re able to give patients.  

If a patient has advanced kidney failure, which can sometimes happen, or if you have to focus more on protecting their bones and if there’s concern about fractures and things like that. And then independent of patient characteristics in terms of overall health, the last part I talk to patients about is their own preferences. It’s a hard thing to talk about, shared decision-making in a cancer that most people have never heard about, but there is certainly – when we talk about options and there are, it’s important to talk about shared decision-making in terms of what’s most important to them and where they – and most patients will say, “Well, I just want the best medicine.”  

And I say to them, “Well, you know, we have lots of options, and that’s the best thing about it, but we also want to be cognizant of the real world, of giving best options,” and for example, Many of my patients – so, I’m at The Ohio State University, I’m here. And a lot of patients travel. I have a lot of older patients that I care for, and they’re very independent with travel. And I want to make sure that whatever therapies we’re getting for them, that we can do this in such a way that maintains their lifestyle.  

So, the beginning part of a treatment, it is broadly described as – when we talk about someone who was diagnosed with this, it’s this thing called induction. So, induction is when we give anywhere from two to four medications to be able to control their cancer and put it into remission. And we know that the cancer is in remission because, like we started out the conversation with Dr. Cottini, myeloma makes proteins. Oftentimes, it makes proteins, those proteins are not nutrition proteins but are cancer proteins that we can track in the blood. 

So, we can check them every month and to make sure that the patients are having a really good response, and as such, we’re able to define that they’re responding to their treatment. Because they have a beginning stage in induction, which they’re given treatment, and then the goal is to put patients put in remission.  

Depending on the overall health of the patient, a standard of care for most patients diagnosed with multiple myeloma is to undergo an autologous stem cell transplant. An autologous stem cell transplant is not a transplant in which you’re getting cells from your brother or sister and they’re being donated to you. They are your own stem cells. We get them out of you when your bone marrow is free of disease, and then we would admit you to the hospital for a more intensive therapy and give them back. 

That is often the standard of care for patients newly diagnosed with multiple myeloma, and it is recommended for most patients. Some patients get – I like to think of it as a stem cell transplant not at the time of their initial diagnosis, but later on at the time of relapse, or some patients are not candidates for a transplant or elect not to have a transplant. And all of these options are very personalized to the patient. It’s very hard to say that this is exactly what we do. 

Because it’s a strategy where it requires a lot of shared decision-making to make sure that we’re getting good disease control, good quality of life, and deep, deep remissions for our patients. So, then, if a patient gets a transplant, there’s a period of recovery, and then patients go on a pill most often, a maintenance pill that they stay on for indefinitely. 

Myeloma is also a cancer which has perpetual therapy. Very different than many other cancers, where there’s a beginning and an end, myeloma for the most part is perpetual therapy, where you get some form of therapy at higher dosages versus lower dosages over a period of time.   

So, I’m going to talk broadly about the classes of drugs that we have and how we use them to be able to define therapy. 

So, the first class of drugs are called proteasome inhibitors. Just like many other cancers, we use different types of drugs to be able to target different aspects of a cancer cell’s growth cycle.  

So, very similar to how we do other drugs, these are very specific to the cancer cell, and they’re very targeted. So, unlike some of our other kind of classic chemotherapies, many of these medicines that I’m going to talk about are very targeted at the cancer cells without causing too many other problems. 

So, proteasome inhibitors include drugs like bortezomib (Velcade), which is given as a shot, carfilzomib (Kyprolis), which is given as an IV, or ixazomib (Ninlaro), which is given as a pill. They have different indications, but they’re the same class of drugs.  

The next class of drugs is called immunomodulatory drugs, or iMiDs. This includes things like lenalidomide (Revlimid), pomalidomide (Pomalyst). Those are the most common, and then we sometimes use the drug that the original iMiD drug, which is called thalidomide (Contergan). 

These are all pills that patients take, and so that’s oftentimes very nice for patients to be able to provide therapy at home, very well-tolerated. The next class of drugs are called monoclonal antibodies. On a cancerous cell, there is a marker. 

And so, we use monoclonal antibodies to be able to target the marker on the cancer cell. What that means is very specific. To that cancer cell, so, the most common target is the CD38, that’s a marker on one of the cancer cells. And we use a drug called daratumumab (Darzalex), that can be given as an IV or a subcutaneous agent, or another drug called isatuximab (Sarclisa). We also have other markers on the plasma cell. There’s a marker called SLAMF7, which we have other drugs called elotuzumab (Empliciti), which is often used for patients more in the relapse setting. 

How Do Myeloma Test Results Influence Prognosis and Care?

/in , , , , , , , /by

How Do Myeloma Test Results Influence Prognosis and Care? from Patient Empowerment Network on Vimeo.

Key testing is important for understanding myeloma, but how do results impact care and treatment? Myeloma experts Drs. Ashley Rosko and Francesco Cottini discuss how test results can affect care options and encourage patients to discuss results with their healthcare team.

Dr. Ashley Rosko is Medical Director of the Oncogeriatric Program at the Ohio State University Comprehensive Cancer Center – The James. Learn more about Dr. Rosko.
 
Dr. Francesca Cottini is Assistant Professor in the Division of Hematology at the Ohio State University Comprehensive Cancer Center. Learn more about Dr. Cottini.

See More From INSIST! Myeloma

Related Programs:

How Close Is Personalized Medicine for Myeloma?

How Close Is Personalized Medicine for Myeloma?

 What Tests Are Essential to Understand a Myeloma Diagnosis?

What Tests Are Essential to Understand a Myeloma Diagnosis?

 Making Treatment Decisions: Understanding Common Myeloma Therapies

Making Treatment Decisions | Understanding Common Myeloma Therapies

Transcript:

Katherine:

Dr. Rosko, what do the results of these tests tell you about prognosis? 

Dr. Rosko:

Yeah, I think this is a really important question. And, in my experience, when we encounter a patient newly diagnosed with myeloma, it is like drinking from a firehose in terms of the amount of information that we are reviewing and the amount of information that we are discussing with the patient and with their family. And oftentimes, we talk about this piece of these cytogenetic abnormalities, and we talk about – but I really encourage your patients and anyone who is listening in today to really take a deeper dive. 

Because sometimes it’s helpful as, one, you’re navigating a new cancer diagnosis, but that’s challenging in and of itself. And then, two, talking about a cancer, multiple myeloma, that is – most people don’t know so much about multiple myeloma, unlike breast or colon or lung cancer, and so I really encourage patients and their caregivers. And a lot of times this happens, where we’ll go over all the cytogenetic abnormalities, we’ll talk about how it plays a role in their overall treatment trajectory, and their prognosis, but also good just to circle back and say. 

Settling into what this diagnosis is, oftentimes, people on first time treatment. And then even sometimes months or even years into their diagnosis, they stop and they come back and they say, “Can we talk about this FISH data?  

Can we talk about what changes that I had within the DNA? What does this mean?” And that’s not uncommon at all.  

So, I really feel like for many people that are on the call here today, I think it’s important to say it’s okay to go back to your physician and say, “I’m learning more about this, now that I’m more familiar with what this diagnosis is, can we talk about these FISH changes, or can we talk about the stage of my cancer?” Because I think it’s oftentimes an overwhelming period of time to have a new cancer diagnosis. And I also want to just give permission to everyone on the call that it’s okay to go back and ask questions, even if it’s been months or years.  

So, having high-risk mutation can upstage a cancer and in the absence of high-risk mutations can downstage a cancer. So, what that really means is saying, “These biologic changes that are happening in the cancer cells give a sense of what we anticipate that the trajectory is going to be when someone is diagnosed.” 

Now, it’s imperfect. I feel like cancer just generally is unpredictable, and there are many things that we try as clinicians. And especially with the experience that we have, to say, “This is what we anticipate the course will be like you, in terms of response, in terms of the cancer being quiet.” As you all know, multiple myeloma is not a curable cancer right now. And for all patients, when they’re diagnosed, they’re often able to get disease control and be able for that cancer to be put in remission. And we do focus on remission. 

I think that’s also something that I talk to my patients about. Even though we can’t cure it, we can certainly control it, and that’s a big part of what we do. So, when we get good disease control, we’ll talk more about next therapies, but that is how Dr. Cottini – Dr. Cottini is a wonderful scientific investigator and knows all of the latest and greatest when it comes to different mutations that are identified within cancer cells. We partner very closely with her in terms of  scientific investigation and how the mutations that were newly identified, too, play a role in terms of response to treatment, and how we’re able to best treat them. 

Katherine:

Thank you for that. Dr. Cottini, do you have anything to add as far as what type of questions patients should ask their healthcare team about test results?  

Dr. Cottini:

I mean, I think Dr. Rosko already pointed out the most important things. So, multiple myeloma is a rare disease, and it’s not as intuitive to understand as breast cancer, lung cancer, prostate cancer. 

So, it’s really important as a patient to understand which tests are we ordering. Why are we ordering? How do we monitor the disease? Because that’s one of the most important questions the patient asks, because for different types of solid tumor, we get imaging, and we know that the tumor is growing or not. Where, for us, we look at the markers I had described previously. And sometimes, we maybe see small changes in the markers that are very concerning and worrisome for the patient, but sometimes they are not. So, I think asking questions about the testing and how we treat them and monitor the disease is a very important part of being a good applique for itself.  

How Close Is Personalized Medicine for Myeloma?

/in , , , , , , , /by

How Close Is Personalized Medicine for Myeloma? from Patient Empowerment Network on Vimeo.

Therapy targeting specific mutations or abnormalities is becoming increasingly common in cancer care, but are we there in myeloma? Dr. Ashley Rosko discusses how clinicians are using test results and patient factors to move closer to individualizing myeloma care.

Dr. Ashley Rosko is Medical Director of the Oncogeriatric Program at the Ohio State University Comprehensive Cancer Center – The James. Learn more about Dr. Rosko.

Download Resource Guide

See More From INSIST! Myeloma

Related Programs:

What Tests Are Essential to Understand a Myeloma Diagnosis?

What Tests Are Essential to Understand a Myeloma Diagnosis?

How Do Myeloma Test Results Influence Prognosis and Care?

How Do Myeloma Test Results Influence Prognosis and Care?

 Making Treatment Decisions: Understanding Common Myeloma Therapies

Making Treatment Decisions | Understanding Common Myeloma Therapies

Transcript:

Katherine:

Dr. Rosko, in many other cancers, we’ve been hearing about targeted therapies and immunotherapies. In some cases, a specific mutation or chromosomal abnormality may indicate that a particular treatment may be effective. Are we there yet in multiple myeloma care? 

Dr. Rosko:

Yeah, so, myeloma care is always a little bit different. So, myeloma, being a blood cancer, is different than other solid tumors, and how we treat it is also a bit different. So, unlike solid tumors, in which we look at the size of a cancer and then if it’s in different places in the body. In multiple myeloma, it being a blood cancer, just by definition it’s throughout the body. So, we have to be able to estimate or stage cancers differently or stage myeloma differently. And it is based upon the cytogenetics that Dr. Cottini just outlined to you.  

So, to get back to your question, Katherine, I didn’t forget about, how do we define treatment, how are some of these therapies being defined specifically and personalized for persons with multiple myeloma? And we do do that. And it is based a lot upon the DNA of those cancer cells and whether or not they’ve acquired what I would call a standard-risk changes or whether or not they’ve acquired a biology that makes them tend to act more aggressively. Now, again, these DNA differences – not all cancers follow the book, and not all therapies are unique to these. 

But what it does help us to do as clinicians to say, “Well, we have standard risk mutations within these cancer cells, and then we can define oftentimes how many drugs a patient gets when they’re newly diagnosed. Just like many other cancers, our treatments for multiple myeloma can be a combination of pills or shots. And then, if patients carry mutations that tend to act more aggressively, we tend to be very aggressive with their upfront therapy. For many patients, would receive three medications. Patients with more aggressive disease biology may receive four medications. 

And it’s very unique upon many characteristics. It’s not only based upon the cancer cells’ DNA but also the health of the patient. The health of the patient really defines also the ability to tolerate treatment. So, many patients are – myeloma has a lot of heterogeneity to it, where some patients with myeloma can’t believe that they could possibly have this cancer. 

You know, it’s really kind of picked up subtly, with blood abnormalities. And then some patients with myeloma come into the hospital very very sick, with having kidney damage or having infection. And it runs the gambit between being asymptomatic really and having patients coming in quite unwell. That also influences our treatment decisions. So, when we think about the question about whether we have different immunotherapies or targeted therapies based upon the genetic changes within the myeloma cancer cells, the answer is yes, we do shape therapy that’s tailored around the type of abnormalities within the cancer cells. 

But unlike some cancers, where if the cancer cells carry a specific marker, we give a specific drug, that’s not quite where we’re at with multiple myeloma, in terms that providing therapy is saying, “If you carry this mutation, this is what you should get.” 

So, it’s a very long answer to say to you that we do personalize therapy based upon changes within the DNA, but we also base it upon how fit the patient is and how their health was prior to developing cancer.  

Katherine:

Dr. Cottini, what mutations or abnormalities are you looking for? 

Dr. Cottini:

So, as Dr. Rosko said, and as I quickly previously mentioned, so there are different types of DNA tests that we can do. One is this FISH test, and that’s a standard test. It’s usually done practically everywhere. And it practically tells us if there are specific deletions or changes. 

And we don’t really have yet a specific medication that we know works for specific abnormalities. But all this information is important to decide, as Dr. Rosko said, number of drugs, and maybe that can be helpful in the future when hopefully thanks to the research, we will be able to say, “Based on this abnormality, you would benefit more from this type of treatment.”  

There are other types of tests. One is called DNA testing, so we look at the mutation. So, really to point to small changes of a particular gene. This is done not routinely, but I think it can still give lots of good information. And there are lots of genes that are normally myeloma, that has potential drugs that have been studied, those with multiple myeloma and any other type of cancer.  

What Tests Are Essential to Understand a Myeloma Diagnosis?

/in , , , , , , , /by

What Tests Are Essential to Understand a Myeloma Diagnosis? from Patient Empowerment Network on Vimeo.

Myeloma diagnoses can vary greatly, so it’s important to understand an individual’s disease before choosing a treatment approach. Dr. Francesca Cottini outlines the tests to better understand myeloma and explains the purpose of in-depth cytogenetic testing.
 
Dr. Francesca Cottini is Assistant Professor in the Division of Hematology at the Ohio State University Comprehensive Cancer Center. Learn more about Dr. Cottini.

See More From INSIST! Myeloma

Related Programs:

How Close Is Personalized Medicine for Myeloma?

How Close Is Personalized Medicine for Myeloma?

 How Do Myeloma Test Results Influence Prognosis and Care?

How Do Myeloma Test Results Influence Prognosis and Care?

 Making Treatment Decisions: Understanding Common Myeloma Therapies

Making Treatment Decisions | Understanding Common Myeloma Therapies

Transcript:

Katherine:

Part of accessing more personalized care starts with test results. Dr. Cottini, what testing should take place following a myeloma diagnosis?  

Dr. Cottini:

So, once somebody is diagnosed with multiple myeloma, there are different types of tests that we need to get. Some are blood tests, some are urine tests, some are bone marrow tests, and others are just different types of imaging. So, the reason for all these tests is because multiple myeloma can kind of go everywhere and can cause the damage to different types of organs. 

So, if we look at blood tests, usually you would see that you get the complete blood count, so we can count the number of red blood cells, white blood cells, and platelets. And then we’ll look at kidney function, through a chemistry profile, calcium levels, multiple myeloma can affect bone cells can affect kidneys. And then, you will see some more sophisticated tests that are really important for the diagnosis of multiple myeloma but also for monitoring and seeing if you’re actually responding to the treatment or you are progressing. 

These two tests that you can see are kind of difficult to say, but very important and needs to be remembered. So, one is called serum protein electrophoresis with immunofixation. And the other one is free light chain assays. 

And the practicum with these two tests is we can identify the specific marker of the multiple myeloma cells and it is either something monoclonal protein or M-protein or kappa light chain numbers. And as I said before, these numbers can be monitored. So, in response to the treatment, they should go down. And then, unfortunately, if we see progression, they might go up again.

And then, urine tests can also give the same type of numbers. Usually, we have our patient keep the urine for 24 hours, for a day, and we can see if there’s monoclonal proteins or light chains there, too. Then there is a least favorite test of all of them that is the bone marrow testing. So, this is very important for us, because it’s where most of the myeloma cells stay. So, we need to have a look at the bone marrow. 

We need like a piece of the bone and some of the liquid tissue to look at specific characteristics of the myeloma. And then, I said before, the myeloma can go to bones, so we need to kind of get some imaging of the bones. These are usually a set of X-rays – it’s called skeletal survey – to see if there is any area that is abnormal or at risk of fractures.  

Then, we are also looking at PET scan, which is a more sophisticated test that is based on sugar consumption. We know that myeloma cells and all cancers enjoy sugar, so with the PET scan, we can see visually where the myeloma cells are in the body.  

Katherine:

What is cytogenetics? 

Dr. Cottini:

So, this is a really interesting question. So, cytogenetics, or FISH tests, are tests that practical tests  allow us to look at the chromosomes of the multiple myeloma. 

So, everybody has 46 chromosomes, right? Multiple myeloma cells can have more of them or less of them. So, they can have – some myeloma cells have 17 chromosomes instead of 46. So, cytogenetics in the karyotype counts how many chromosomes there are. And then, there is another type of test that is called FISH test, or fluorescence in situ hybridization – I get all the difficult names – that practically look at specific area of chromosome. It can tell us if some areas of chromosomes are lost. That’s what you can read as deletions, or practically missing pieces of chromosomes. 

Or there are extra pieces of chromosomes. These are the amplification gains. Or if there are different pieces of chromosomes that stick together. And these are the translocational chromosomes. And all of these data are important for deciding for knowing how aggressive or difficult to treat the myeloma.  

Katherine:

Dr. Cottini, what mutations or abnormalities are you looking for? 

Dr. Cottini:

So, as Dr. Rosko said, and as I quickly previously mentioned, so there are different types of DNA tests that we can do. One is this FISH test, and that’s a standard test. It’s usually done practically everywhere. And it practically tells us if there are specific deletions or changes. 

And we don’t really have yet a specific medication that we know works for specific abnormalities. But all this information is important to decide, as Dr. Rosko said, number of drugs, and maybe that can be helpful in the future when hopefully thanks to the research, we will be able to say, “Based on this abnormality, you would benefit more from this type of treatment.”   

There are other types of tests. One is called DNA testing, so we look at the mutation. So, really to point to small changes of a particular gene. This is done not routinely, but I think it can still give lots of good information. And there are lots of genes that are normally myeloma, that has potential drugs that have been studied, those with multiple myeloma and any other type of cancer.  

Developing Research and New Myeloma Treatment Options

/in , , , , , , , /by

Developing Research and New Myeloma Treatment Options from Patient Empowerment Network on Vimeo.

What are the new developments in myeloma treatment and research? Dr. Brandon Blue discusses how the landscape of myeloma care has changed in recent years and treatment options for high-risk myeloma, and he shares developing research that patients should know about.

Dr. Brandon Blue is Assistant Member and Clinical Instructor in the Department of Malignant Hematology at Moffitt Cancer Center in Tampa, FL. Learn more about Dr. Brandon Blue.

See More from Evolve Myeloma

Related Resources:

What Myeloma Patients Need to Know About Bispecific Antibodies

What Myeloma Patients Need to Know About Bispecific Antibodies

 Myeloma CAR T-Cell Therapy_ How Does It Work and What Are the Risks

Myeloma CAR T-Cell Therapy: How Does It Work and What Are the Risks?

 How Is High-Risk Myeloma Assessed

How Is High-Risk Myeloma Assessed?

Transcript:

Katherine Banwell:

Dr. Blue, the landscape of myeloma care has changed significantly in recent years. Are there new factors to consider when working with a patient to choose a treatment approach?   

Dr. Brandon Blue:

Yeah. The good thing about myeloma is it’s literally always changing, and that’s a great thing. Compared to some of the other cancers, or really even other diseases, sometimes we’ve been using the same things since the ‘90s. But luckily for myeloma every couple years we get something that’s bigger, and typically better. So, right now some of the new things that are available for patients are all the way from newly diagnosed, all the way to people who have relapsed disease. So, we have a lot of different options that we can potentially go into.  

Katherine Banwell:

Dr. Blue, what treatment options are available for myeloma that’s considered high-risk?  

Dr. Brandon Blue:

Yeah. So, unfortunately, there’s some people who have multiple myeloma whose disease does not follow the standard pattern. Unfortunately, what happens is that there are certain mutations that actually happen in the biology of those cancer cells that actually cause them to survive when they should be dying. And unfortunately, that means that sometimes the chemotherapy and the medicines that we give them becomes a little bit more resident. 

A lot of times when we give people treatment the one question they ask is, “How long will it last?” But, unfortunately, there’s some people who have those high-risk features that unfortunately, despite whatever numbers we tell them of how long it may last, theirs actually may last a little bit shorter, and the disease may come back a little bit quicker. So, what we have to do as the doctors, and as the team, taking care of these patients is maybe do things a little bit more outside of the box, and do things that might tend to be a little bit more aggressive. 

Because sometimes we have to match the aggressiveness of the disease. If the cancer itself is starting to be high-risk or aggressive, sometimes we may have to do some nontraditional things to kind of make sure that they have a good outcome and a good result.  

Katherine Banwell:

Dr. Blue, is there developing research that myeloma patients should know about? And what are you hopeful about?  

Dr. Brandon Blue:

Yeah. One of the things that happens right now is that we have CAR T that’s available for patients got approved by the FDA. However, the CAR T product that we currently have available only have one target, which is called the BCMA, or B-cell maturating antigen. 

Which is part of the plasma cells, however, there are so many other targets on the plasma cells that potentially can be targets for new medications. And the good thing is that there are actually new CAR T and medications that are being developed that actually target other things other than the BCMA.  

So then, it may come to the point where people get more than one CAR T down the road, and I think those are exciting clinical trials. Because if there’s multiple targets, and there’s multiple CAR T, maybe we can sequence them in a way that maybe we find a cure for the disease one day.  

Katherine Banwell:

That’s exciting.  

Dr. Brandon Blue:

It is.  

Katherine Banwell:

Dr. Blue, thank you so much for joining us. Do you have anything else you’d like to mention?  

Dr. Brandon Blue:

I just want people to know that it’s okay to get a second opinion. I think that regardless of what’s happening in your care, sometimes it’s always good just to have someone, especially someone who’s what they call a myeloma specialist, to review your case, and just make sure that you’re on the right road, and that things are going well for you. So, it’s something that I would recommend for anyone to do. 

How Is Bispecific Antibody Therapy Changing Myeloma Care?

/in , , , , , , , /by

How Is Bispecific Antibody Therapy Changing Myeloma Care? from Patient Empowerment Network on Vimeo.

How does bispecific antibody therapy work? Dr. Brandon Blue explains the benefits of bispecific antibody therapy and how this treatment may be quicker to access for patients.

Dr. Brandon Blue is Assistant Member and Clinical Instructor in the Department of Malignant Hematology at Moffitt Cancer Center in Tampa, FL. Learn more about Dr. Brandon Blue.

See More from Evolve Myeloma

Related Resources:

What Myeloma Patients Need to Know About Bispecific Antibodies

What Myeloma Patients Need to Know About Bispecific Antibodies

 Myeloma Treatment: Who Is Stem Cell Transplant Appropriate For

 Questions and Considerations When Making Myeloma Treatment Decisions

Questions and Considerations When Making Myeloma Treatment Decisions

Transcript:

Katherine Banwell:

Dr. Blue, can you tell us about bispecific antibody therapy for myeloma?  

Dr. Brandon Blue:

Yeah. So, bispecific is basically similar to CAR T in a way that it uses the body’s immune system. But the big difference with bispecific therapy is that not only does it attack the plasma cell, which is the typical cancer cell in multiple myeloma, but it also brings the cancer cell to the actual immune system. 

So, it’s one thing to kind of go after the cancer cell, it’s another thing to say, “Hey, here’s the immune system, here’s the cancer cell. Let me figure out a way to marry the two of them together so that the fighting really takes place in real time.” And luckily, we’ve seen some really fantastic results.  

Katherine Banwell:

So, how is this therapy changing myeloma care? 

Dr. Brandon Blue:

The big thing about bispecifics is that they’re a much quicker process than CAR T.  

Right now, one of the things that is slowing up the CAR T process is something called manufacturing time. And so, even if someone wanted CAR T today, they may not be able to get it for six to eight weeks due to that manufacturing time. However, these bispecific are typically readily available so that if you need them today, probably by tomorrow, the next day, they can be infused. And so, that’s a much quicker time, and that allows patients to get the treatment that they need. 

Because, again, these are patients who, unfortunately, disease has not responded to a lot of the more traditional therapies. So, they need help, and sometimes they need help quickly. 

Accessing Myeloma CAR T-Cell Therapy Clinical Trials

/in , , , , , , , /by

Accessing Myeloma CAR T-Cell Therapy Clinical Trials from Patient Empowerment Network on Vimeo.

How has CAR T-cell therapy changed the landscape of myeloma care? Dr. Brandon Blue shares how this therapy has been a “game changer” in myeloma care, and how clinical trials for newer CAR T-cell therapies are advancing care and access for patients.

Dr. Brandon Blue is Assistant Member and Clinical Instructor in the Department of Malignant Hematology at Moffitt Cancer Center in Tampa, FL. Learn more about Dr. Brandon Blue.

See More from Evolve Myeloma

Related Resources:

Considering CAR T-Cell Therapy for Myeloma_ Key Questions to Ask Your Doctor

 Questions and Considerations When Making Myeloma Treatment Decisions

Questions and Considerations When Making Myeloma Treatment Decisions

Transcript:

Katherine Banwell:

Dr. Blue, we know that the approved CAR T-cell therapies are for patients who have already undergone several lines of treatment. How has this therapy revolutionized care for myeloma patients?  

Dr. Brandon Blue:

Yeah. So, CAR T is really a game changer when it comes to multiple myeloma. I’ll tell you that previously people have seen a lot of the best medicines that we have, and unfortunately for a good percentage of people the disease just becomes what we call refractory.  

And unfortunately, despite us giving them the best medicines, the disease still likes to survive. So, we had to think of something of what can still kill cancer, but may not be the traditional chemotherapy that people may think of? So, we say, “Well, let’s come up with CAR T because it’s a way to actually use the body’s own immune system to fight off those cancer cells.” And for myeloma it really has shown a lot of progress. And one of the things that we know now is that not only do we have one, but we have two products, and maybe even a third coming down the pipeline because there’s more and more of this CAR T becoming available. 

And that’s better, and better for patients.  

Katherine Banwell:

Absolutely. That’s great news. For patients who are recently diagnosed, Dr. Blue, is there any chance of accessing this treatment sooner? Maybe through clinical trials. 

Dr. Brandon Blue:

Yeah. One of the biggest clinical trials that I think that people are excited about is trying to challenge something that we’ve been doing since the 1980s, which is stem cell transplant.  

So, typically, when a person get diagnosed with multiple myeloma, especially newly diagnosed, stem cell transplant is typically part of the treatment plan. But now there’s clinical trials that are coming out where we challenge instead of maybe a patient going to stem cell transplant, maybe they might do CAR T instead. And we’re trying to figure out can something that we’ve been doing since the ‘80s be un-throned as the best standard practice? And so, I think that’s something that people are really excited about, that’s something I’m excited about. 

And it gives people who are newly diagnosed a chance to get some of this novel therapy.   

Katherine Banwell:

I have a follow-up question about the clinical trials, you mentioned that there is one going on. Where is it taking place?  

Dr. Brandon Blue:

Yeah. So, it’s actually a multi-center study. And so, hopefully, we hope to have Moffit Cancer Center involved in that clinical trial, but it’s multiple different sites really all over the world because I think this is a question that everybody’s really excited about. Again, like I said, transplant has been happening since 1980s, and so for some treatment to come along to potentially challenge that, I think people are excited about a new contender. And we’ve already seen the progress that CAR T has already made. 

And so, the big question is how well will it work when someone is newly diagnosed before their body has really seen all the extra treatments that are there? Will it work even better?  

We’re very hopeful, and we’re very optimistic. 

Katherine Banwell:

Where can people find out about this particular clinical trial and other clinical trials?  

Dr. Brandon Blue:

Yeah. So, I tell people there’s so many different websites and resources. One of the main ones that is very readily accessible is clinicaltrials.gov, is very kind of easy, and intuitive. Typically, what you can do at clinicaltrials.gov is you can literally kind of just type in your disease process, and then they’ll tell you if it’s newly diagnosed, or relapsed. There’s also a place called SparkCures. SparkCures is fantastic organization that really tries to focus people, and get them matched with clinical trials, which is fantastic.  

There’s also HealthTree. HealthTree not only helps people from a clinical trial standpoint, but they also have patient support programs because nobody wants to be in the fight for cancer by themselves. The American Cancer Society does a fantastic job, as well as Leukemia & Lymphoma Society. 

The International Myeloma Foundation, or the IMF, and then the MMRF, the Multiple Myeloma Research Foundation. And there’s many more, but those are some of the top ones that we readily use that have a lot of information. And some of them have not only information for the patient, but also information for the family, and the caregivers. Because again, when someone gets diagnosed with cancer it doesn’t just affect the person, it affects the whole family.  

How Are Myeloma Patients in Remission Monitored?

/in , , , , , , , /by

How Are Myeloma Patients in Remission Monitored? from Patient Empowerment Network on Vimeo.

How often should testing be administered when myeloma is in remission? Dr. Brandon Blue discusses how patients in remission are monitored and when a bone marrow biopsy may be required.

Dr. Brandon Blue is Assistant Member and Clinical Instructor in the Department of Malignant Hematology at Moffitt Cancer Center in Tampa, FL. Learn more about Dr. Brandon Blue.

See More From INSIST! Myeloma

Related Programs:

Stem Cell Transplants for Myeloma: An Update

Stem Cell Transplants for Myeloma: An Update

 Should You Push for a Stronger Myeloma Treatment at Relapse

Should You Push for a Stronger Myeloma Treatment at Relapse?

 Questions and Considerations When Making Myeloma Treatment Decisions

Questions and Considerations When Making Myeloma Treatment Decisions

Transcript:

Katherine Banwell:

Dr. Blue, how often should bone marrow biopsy be performed in the years following a stem cell transplant?  

Dr. Brandon Blue:

So, typically following stem cell transplant patients are kind of switched to what we call maintenance therapy.  

Meaning that the disease is typically under control after transplant, and our job right now is to kind of put the lid on the disease and keep that lid on so that the disease doesn’t kind of bubble over. And likely, people are on that maintenance therapy for three, four, sometimes even five years, or more. And so, sometimes when the disease is very stagnant or very stable, and people are on maintenance therapy, there may not be a need for multiple repeated bone marrow biopsies. 

Because the disease may just be in a kind of dormant or remission stage. However, at the first sign that we see that things are changing, we see that unfortunately the disease may be starting to relapse, or maybe even there’s a new pain, or things happening that just need further investigation, I think a bone marrow biopsy would be very warranted at that time.  

Katherine Banwell:

Okay. So, when patients are in a kind of remission stage you just monitor them. Do you continue to do bloodwork, and test their urine, and so on?  

Dr. Brandon Blue:

Blood, urine, imaging. Blood, urine imaging. 

Katherine Banwell:

Yeah. Blood, urine, imaging.   

Dr. Brandon Blue:

Yup. Those would be the best ways to follow it. Of course, the gold standard would be a bone marrow biopsy, but typically what happens is that the blood, the urine, and the imaging typically reflect what’s happening in the bone marrow. It’d be sometimes very unlikely for a patient’s bloodwork to be normal, but then the bone marrow to be ridden with cancer. Typically, it doesn’t work that way. There are some unique circumstances where bone marrow biopsies are needed in people who have something called non-secretory myeloma, but that’s a very small percentage. 

What Testing Is Appropriate for People With Smoldering Myeloma?

/in , , , , , , , /by

What Testing Is Appropriate for People With Smoldering Myeloma? from Patient Empowerment Network on Vimeo.

How is smoldering myeloma monitored? Myeloma expert Dr. Brandon Blue explains why treatment is not necessary and the types of tests that are used to monitor this diagnosis.

Dr. Brandon Blue is Assistant Member and Clinical Instructor in the Department of Malignant Hematology at Moffitt Cancer Center in Tampa, FL. Learn more about Dr. Brandon Blue.

See More From INSIST! Myeloma

Related Programs:

How Are Myeloma Patients in Remission Monitored

How Are Myeloma Patients in Remission Monitored

 Myeloma Combination Therapy _ What Patients Should Know

Myeloma Combination Therapy: What Patients Should Know

 Questions and Considerations When Making Myeloma Treatment Decisions

Questions and Considerations When Making Myeloma Treatment Decisions

Transcript:

Katherine Banwell:

What testing and treatments are appropriate for smoldering myeloma? And first, could you define smoldering myeloma for us?  

Dr. Brandon Blue:

Yeah. So, one of the things that makes multiple myeloma kind of a very difficult disease is that it can attack people’s bones.  

When people have the smoldering myeloma, they have none of those bone disease. When people typically have multiple myeloma it can affect their kidneys, and actually cause low blood counts called anemia.  

When people have smoldering, they don’t have any of those classic features, however, they still may have a burden of cancer cells. Anywhere from 10 to 59 percent of plasma cells is really still considered this smoldering, or inactive cancer, but it’s still cancer. And so, we know that roughly in the first five years about 10 percent of those patients will go from this inactive smoldering stage to the active myeloma and required treatment. 

A lot of times we do observation for those patients to kind of make sure that they get the treatment when they need it. There is some studies to show that some people do get treatment during the smoldering stage, but for a lot of times observation is needing because sometimes it can be several years really before someone would need treatment. 

And a lot of times we try not to expose people to treatment if it’s really not necessary at the time.  

Katherine Banwell:

I see. So, it’s more of a watch and wait. 

Dr. Brandon Blue:

Exactly right. And sometimes you actually watch and wait, and then you keep watching, and waiting, and sometimes people never develop the active disease. And so, especially in those patients, you would’ve exposed them to chemotherapy that they really never needed. And one thing that I always tell my patients is that it’s important to know that you have cancer cells, but it’s also important for us to follow it. We are here to help and support you, right? And having cancer in your body sometimes can be very anxiety-provoking. 

And so, for a lot of patients who are in that category, sometimes we offer them clinical trials that we have available to say, “Hey, this is something that we’re trying to explore and learn more about smoldering myeloma. And maybe this is something that may benefit you.” 

Katherine Banwell:

Yeah. Can a patient with smoldering myeloma be monitored through blood work? Is that something you would do?  

Dr. Brandon Blue:

Yeah. So, typically what we try to do because the disease is so multifaceted, meaning that myeloma is not the same for each person. So, the blood is a fantastic way of following the disease, and monitoring, however, we need to do a little bit more than that. We also like to collect urine because, again, multiple myeloma can affect people’s kidneys. And the good thing about urine is that we flush it down the toilet all the time, but there’s so much information that gets flushed down that we really can learn about the disease and learn about the person by following the urine over time. 

The next thing is that we can follow imaging because, again, multiple myeloma can affect people’s bones. Sometimes if you get aches, and pains, we don’t know if that’s the muscle, we don’t know if that’s a ligament, we don’t know if that’s the bone. Pain is such a subjective thing, so we need to follow people, and have them be monitored with imaging. So, I think that combination of blood, urine, and imaging would be the best thing to do. 

Accessing Personalized Myeloma Treatment | What Patients Should Know

/in , , , , , , , /by

Accessing Personalized Myeloma Treatment | What Patients Should Know from Patient Empowerment Network on Vimeo.

Myeloma experts Dr. Francesca Cottini and Dr. Ashley Rosko provide an overview of the latest advances in essential testing for myeloma and explain how results could affect care and treatment decisions. Drs. Cottini and Rosko also review available myeloma therapies and their hopes for the future of patient care.

Dr. Francesca Cottini is Assistant Professor in the Division of Hematology at the Ohio State University Comprehensive Cancer Center. Learn more about Dr. Cottini.

Dr. Ashley Rosko is Medical Director of the Oncogeriatric Program at the Ohio State University Comprehensive Cancer Center – The James. Learn more about Dr. Rosko.

Download Resource Guide

See More From INSIST! Myeloma

Related Programs:

What Should You Ask Your Doctor About Myeloma Testing_

What Should You Ask Your Doctor About Myeloma Testing?

 How Is Myeloma Treatment Response Measured?

How Is Myeloma Treatment Response Measured?
 How Does Essential Testing Affect Myeloma Care and Treatment (1)

How Does Essential Testing Affect Myeloma Care and Treatment?

Transcript:

Katherine:

Hello and welcome. I’m Katherine Banwell, your host for today’s program. Today we’re going to discuss how to access personalized care for your myeloma and why it’s vital to insist on essential testing.  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. Let’s meet our guests for today. I’ll start with Dr. Ashley Rosko. Dr. Rosko, welcome. Would you please introduce yourself? 

Dr. Rosko:

Hi everyone. My name is Ashley Rosko. I’m an associate professor at the division of hematology at The Ohio State University. 

I’m also the medical director of the oncogeriatric program here at The James and one of the myeloma physicians here at Ohio State. 

Katherine:

Thank you. Also with us is Dr. Francesca Cottini. Dr. Cottini, would you please introduce yourself to the audience? 

Dr. Cottini:

Sure. My name is Francesca Cottini. I am an assistant professor in the divisions of hematology at The Ohio State University. I see patients with multiple myeloma, and I also run my own lab where I focus on multiple myeloma basic research. 

Katherine:

Thank you both for taking the time out of your busy schedules to join us today.  

It’s no secret that it’s important for patients to take an active role in their care and treatment decisions, and I’m sure many viewers here today are doing just that. So, Dr. Rosko, let’s start with this question: Why do you think it’s essential that patients advocate for themselves and insist on better care?  

Dr. Rosko:

Yeah, so I think when it comes to uncommon diseases like multiple myeloma –  

Although we’re talking a lot about it here today, myeloma is an uncommon cancer, and when it comes to rare cancers, it’s really important for you to get care at either a comprehensive cancer center or a place where there is expertise specifically in multiple myeloma. 

And the reason why that’s so important, it’s recommended through the NCCN guidelines and other standing guidelines is because myeloma is a very – it’s a shifting and changing landscape when it comes to both treatment regimens, diagnosis, and there’s a lot of moving parts and pieces.

Such as, there is an uncommon cancer that when diagnosed, we do recommend that patients and with their caregivers and with their families and support be able to seek expertise care for these uncommon cancers. We work often in collaboration with our community team, but we would not be able to care for myeloma if it were not for our community partners. 

And so, it’s really, really important for patients oftentimes, when there’s been such a diagnosis, they can come to a comprehensive cancer center for a consultation or to be able to get a second opinion oftentimes. And then continue to get care locally. It really provides this overall guidance on the management and diagnosis of uncommon plasma cell disorders, and we’re happy to do that. 

Katherine:

Thank you for that. It’s helpful as we begin our discussion. Part of accessing more personalized care starts with test results. Dr. Cottini, what testing should take place following a myeloma diagnosis?  

Dr. Cottini:

So, once somebody is diagnosed with multiple myeloma, there are different types of tests that we need to get. Some are blood tests, some are urine tests, some are bone marrow tests, and others are just different types of imaging. So, the reason for all these tests is because multiple myeloma can kind of go everywhere and can cause the damage to different types of organs. 

So, if we look at blood tests, usually you would see that you get the complete blood count, so we can count the number of red blood cells, white blood cells, and platelets. And then we’ll look at kidney function, through a chemistry profile, calcium levels, multiple myeloma can affect bone cells can affect kidneys. And then, you will see some more sophisticated tests that are really important for the diagnosis of multiple myeloma but also for monitoring and seeing if you’re actually responding to the treatment or you are progressing. 

These two tests that you can see are kind of difficult to say, but very important and needs to be remembered. So, one is called serum protein electrophoresis with immunofixation. And the other one is free light chain assays. 

And the practicum with these two tests is we can identify the specific marker of the multiple myeloma cells and it is either something monoclonal protein or M-protein or kappa light chain numbers. And as I said before, these numbers can be monitored. So, in response to the treatment, they should go down. And then, unfortunately, if we see progression, they might go up again. 

And then, urine tests can also give the same type of numbers. Usually, we have our patient keep the urine for 24 hours, for a day, and we can see if there’s monoclonal proteins or light chains there, too. Then there is a least favorite test of all of them that is the bone marrow testing. So, this is very important for us, because it’s where most of the myeloma cells stay. So, we need to have a look at the bone marrow.  

We need like a piece of the bone and some of the liquid tissue to look at specific characteristics of the myeloma. And then, I said before, the myeloma can go to bones, so we need to kind of get some imaging of the bones. These are usually a set of X-rays – it’s called skeletal survey – to see if there is any area that is abnormal or at risk of fractures.   

Then, we are also looking at PET scan, which is a more sophisticated test that is based on sugar consumption. We know that myeloma cells and all cancers enjoy sugar, so with the PET scan, we can see visually where the myeloma cells are in the body.

Katherine:

What is cytogenetics? 

Dr. Cottini:

So, this is a really interesting question. So, cytogenetics, or FISH tests, are tests that practical tests allow us to look at the chromosomes of the multiple myeloma. 

So, everybody has 46 chromosomes, right? Multiple myeloma cells can have more of them or less of them. So, they can have – some myeloma cells have 17 chromosomes instead of 46. So, cytogenetics in the karyotype counts how many chromosomes there are. And then, there is another type of test that is called FISH test, or fluorescence in situ hybridization – I get all the difficult names – that practically look at specific area of chromosome. It can tell us if some areas of chromosomes are lost. That’s what you can read as deletions, or practically missing pieces of chromosomes.  

Or there are extra pieces of chromosomes. These are the amplification gains. Or if there are different pieces of chromosomes that stick together. And these are the translocational chromosomes. And all of these data are important for deciding for knowing how aggressive or difficult to treat the myeloma. 

Katherine:

Dr. Rosko, in many other cancers, we’ve been hearing about targeted therapies and immunotherapies. In some cases, a specific mutation or chromosomal abnormality may indicate that a particular treatment may be effective. Are we there yet in multiple myeloma care? 

Dr. Rosko:

Yeah, so, myeloma care is always a little bit different. So, myeloma, being a blood cancer, is different than other solid tumors and how we treat it is also a bit different. So, unlike solid tumors, in which we look at the size of a cancer and then if it’s in different places in the body. In multiple myeloma, it being a blood cancer, just by definition it’s throughout the body. So, we have to be able to estimate or stage cancers differently or stage myeloma differently. And it is based upon the cytogenetics that Dr. Cottini just outlined to you.  

So, to get back to your question, Katherine, I didn’t forget about, how do we define treatment, how are some of these therapies being defined specifically and personalized for persons with multiple myeloma? And we do do that. And it is based a lot upon the DNA of those cancer cells and whether or not they’ve acquired what I would call a standard-risk changes or whether or not they’ve acquired a biology that makes them tend to act more aggressively. Now, again, these DNA differences – not all cancers follow the book, and not all therapies are unique to these. 

But what it does help us to do as clinicians to say, “Well, we have standard risk mutations within these cancer cells, and then we can define oftentimes how many drugs a patient gets when they’re newly diagnosed. Just like many other cancers, our treatments for multiple myeloma can be a combination of pills or shots. And then, if patients carry mutations that tend to act more aggressively, we tend to be very aggressive with their upfront therapy. For many patients, we’d receive three medications. Patients with more aggressive disease biology may receive four medications. 

And it’s very unique upon many characteristics. It’s not only based upon the cancer cells’ DNA but also the health of the patient. The health of the patient really defines also the ability to tolerate treatment. So, many patients are – myeloma has a lot of heterogeneity to it, where some patients with myeloma can’t believe that they could possibly have this cancer. 

You know, it’s really kind of picked up subtly, with blood abnormalities. And then some patients with myeloma come into the hospital very very sick, with having kidney damage or having infection. And it runs the gambit between being asymptomatic really and having patients coming in quite unwell. That also influences our treatment decisions. So, when we think about the question about whether we have different immunotherapies or targeted therapies based upon the genetic changes within the myeloma cancer cells, the answer is yes, we do shape therapy that’s tailored around the type of abnormalities within the cancer cells. 

But unlike some cancers, where if the cancer cells carry a specific marker, we give a specific drug, that’s not quite where we’re at with multiple myeloma, in terms that providing therapy is saying, “If you carry this mutation, this is what you should get.” 

So, it’s a very long answer to say to you that we do personalize therapy based upon changes within the DNA, but we also base it upon how fit the patient is and how their health was prior to developing cancer. 

Katherine:

Thank you for that. Dr. Cottini, what mutations or abnormalities are you looking for? 

Dr. Cottini:

So, as Dr. Rosko said, and as I quickly previously mentioned, so there are different types of DNA tests that we can do. One is this FISH test, and that’s a standard test. It’s usually done practically everywhere. And it practically tells us if there are specific deletions or changes. 

And we don’t really have yet a specific medication that we know works for specific abnormalities. But all this information is important to decide, as Dr. Rosko said, number of drugs, and maybe that can be helpful in the future when hopefully thanks to the research, we will be able to say, “Based on this abnormality, you would benefit more from this type of treatment.”  

There are other types of tests. One is called DNA testing, so we look at the mutation. So, really to point to small changes of a particular gene. This is done not routinely, but I think it can still give lots of good information. And there are lots of genes that are normally myeloma, that has potential drugs that have been studied, those with multiple myeloma and any other type of cancer. 

Katherine:

Yeah. Dr. Rosko, what do the results of these tests tell you about prognosis? 

Dr. Rosko:

Yeah, I think this is a really important question. And, in my experience, when we encounter a patient newly diagnosed with myeloma, it is like drinking from a firehose in terms of the amount of information that we are reviewing and the amount of information that we are discussing with the patient and with their family. And oftentimes, we talk about this piece of these cytogenetic abnormalities, and we talk about – but I really encourage your patients and anyone who is listening in today to really take a deeper dive. 

Because sometimes it’s helpful as, one, you’re navigating a new cancer diagnosis, but that’s challenging in and of itself. And then, two, talking about a cancer, multiple myeloma, that is – most people don’t know so much about multiple myeloma, unlike breast or colon or lung cancer, and so I really encourage patients and their caregivers. And a lot of times this happens, where we’ll go over all the cytogenetic abnormalities, we’ll talk about how it plays a role in their overall treatment trajectory, and their prognosis, but also good just to circle back and say. 

Settling into what this diagnosis is, oftentimes, people on first time treatment. And then even sometimes months or even years into their diagnosis, they stop and they come back and they say, “Can we talk about this FISH data? Can we talk about what changes that I had within the DNA? What does this mean?” And that’s not uncommon at all.  

So, I really feel like for many people that are on the call here today, I think it’s important to say it’s okay to go back to your physician and say, “I’m learning more about this, now that I’m more familiar with what this diagnosis is, can we talk about these FISH changes, or can we talk about the stage of my cancer?” Because I think it’s oftentimes an overwhelming period of time to have a new cancer diagnosis. And I also want to just give permission to everyone on the call that it’s okay to go back and ask questions, even if it’s been months or years.  

So, having high-risk mutation can upstage a cancer and in the absence of high-risk mutations can downstage a cancer. So, what that really means is saying, “These biologic changes that are happening in the cancer cells give a sense of what we anticipate that the trajectory is going to be when someone is diagnosed.” 

Now, it’s imperfect. I feel like cancer just generally is unpredictable and there are many things that we try as clinicians. And especially with the experience that we have, to say, “This is what we anticipate the course will be like you, in terms of response, in terms of the cancer being quiet.” As you all know, multiple myeloma is not a curable cancer right now. And for all patients, when they’re diagnosed, they’re often able to get disease control and be able for that cancer to be put in remission. And we do focus on remission. 

I think that’s also something that I talk to my patients about. Even though we can’t cure it, we can certainly control it, and that’s a big part of what we do. So, when we get good disease control, we’ll talk more about next therapies, but that is how Dr. Cottini – Dr. Cottini is a wonderful scientific investigator and knows all of the latest and greatest when it comes to different mutations that are identified within cancer cells. We partner very closely with her in terms of  scientific investigation and how the mutations that were newly identified, too, play a role in terms of response to treatment, and how we’re able to best treat them.  

Katherine:

Thank you for that. Dr. Cottini, do you have anything to add as far as what type of questions patients should ask their healthcare team about test results?  

Dr. Cottini:

I mean, I think Dr. Rosko already pointed out the most important things. So, multiple myeloma is a rare disease, and it’s not as intuitive to understand as breast cancer, lung cancer, prostate cancer. 

So, it’s really important as a patient to understand which tests are we ordering. Why are we ordering? How do we monitor the disease? Because that’s one of the most important questions the patient asks, because for different types of solid tumor, we get imaging, and we know that the tumor is growing or not. Where, for us, we look at the markers I had described previously. And sometimes, we maybe see small changes in the markers that are very concerning and worrisome for the patient, but sometimes they are not. So, I think asking questions about the testing and how we treat them and monitor the disease is a very important part of being a good applique for itself. 

Katherine:

Thank you. Dr. Rosko, I’d like to move on to treatment. We know that multiple myeloma patients have a number of options and that many available therapies are used in combination. 

So, I’d like you to walk us through the options that are available. 

Dr. Rosko:

So, I’m going to start by how the best way that I can frame out when we talk about newly diagnosed versus patients when they have relapse. So, there are therapies that are available for patients that are FDA-approved when they are newly diagnosed with the cancer, and there are therapies that are approved only when a cancer has acted up again or relapsed. 

So, I’ll kind of frame it from patients who are newly diagnosed. And then, I also will talk more about relapsed therapies and what we’re able to offer to patients. So, in first, when we talk about treatment options, we frame treatment based on a couple things. So, one is, we talk extensively about the disease biology. So, that plays an important role in how we decide which treatment the patient should get.  

And then, the second part about how – I would probably say there’s about four main parts. And so, disease biology is one, and another thing has to do with the patient characteristics. In terms of the patient’s overall health prior to developing cancer, and also how the cancer has impacted their health in terms of everyday activities. Whether or not a person has really slowed down quickly, whether they’ve been in the hospital, and how it’s impacting their organs. Because that plays a role in terms of what we’re able to give patients.  

If a patient has advanced kidney failure, which can sometimes happen, or if you have to focus more on protecting their bones and if there’s concern about fractures and things like that. And then independent of patient characteristics in terms of overall health, the last part I talk to patients about is their own preferences. It’s a hard thing to talk about, shared decision-making in a cancer that most people have never heard about, but there is certainly – when we talk about options and there are, it’s important to talk about shared decision-making in terms of what’s most important to them and where they – and most patients will say, “Well, I just want the best medicine.” 

And I say to them, “Well, you know, we have lots of options, and that’s the best thing about it, but we also want to be cognizant of the real world, of giving best options,” and for example, Many of my patients – so, I’m at The Ohio State University, I’m here. And a lot of patients travel. I have a lot of older patients that I care for, and they’re very independent with travel. And I want to make sure that whatever therapies we’re getting for them, that we can do this in such a way that maintains their lifestyle.  

So, the beginning part of a treatment, it is broadly described as – when we talk about someone who was diagnosed with this, it’s this thing called induction. So, induction is when we give anywhere from two to four medications to be able to control their cancer and put it into remission. And we know that the cancer is in remission because, like we started out the conversation with Dr. Cottini, myeloma makes proteins. Oftentimes, it makes proteins, those proteins are not nutrition proteins but are cancer proteins that we can track in the blood. 

So, we can check them every month and to make sure that the patients are having a really good response, and as such, we’re able to define that they’re responding to their treatment. Because they have a beginning stage in induction, which they’re given treatment, and then the goal is to put patients put in remission. 

Depending on the overall health of the patient, a standard of care for most patients diagnosed with multiple myeloma is to undergo an autologous stem cell transplant. An autologous stem cell transplant is not a transplant in which you’re getting cells from your brother or sister and they’re being donated to you. They are your own stem cells. We get them out of you when your bone marrow is free of disease, and then we would admit you to the hospital for a more intensive therapy and give them back.  

That is often the standard of care for patients newly diagnosed with multiple myeloma and it is recommended for most patients. Some patients get – I like to think of it as a stem cell transplant not at the time of their initial diagnosis, but later on at the time of relapse or some patients are not candidates for a transplant or elect not to have a transplant. And all of these options are very personalized to the patient. It’s very hard to say that this is exactly what we do. 

Because it’s a strategy where it requires a lot of shared decision-making to make sure that we’re getting good disease control, good quality of life, and deep, deep remissions for our patients. So, then, if a patient gets a transplant, there’s a period of recovery, and then patients go on a pill most often, a maintenance pill that they stay on for indefinitely. 

Myeloma is also a cancer which has perpetual therapy. Very different than many other cancers, where there’s a beginning and an end, myeloma for the most part is perpetual therapy, where you get some form of therapy at higher dosages versus lower dosages over a period of time.  

So, I’m going to talk broadly about the classes of drugs that we have and how we use them to be able to define therapy. 

So, the first class of drugs are called proteasome inhibitors. Just like many other cancers, we use different types of drugs to be able to target different aspects of a cancer cell’s growth cycle.  

So, very similar to how we do other drugs, these are very specific to the cancer cell, and they’re very targeted. So, unlike some of our other kind of classic chemotherapies, many of these medicines that I’m going to talk about are very targeted at the cancer cells without causing too many other problems. 

So, proteasome inhibitors include drugs like bortezomib (Velcade), which is given as a shot, carfilzomib (Kyprolis), which is given as an IV, or ixazomib (Ninlaro), which is given as a pill. They have different indications, but they’re the same class of drugs.  

The next class of drugs is called immunomodulatory drugs, or iMiDs. This includes things like lenalidomide (Revlimid), pomalidomide (Pomalyst). Those are the most common, and then we sometimes use the drug that the original iMiD drug, which is called thalidomide (Contergan). 

These are all pills that patients take, and so that’s oftentimes very nice for patients to be able to provide therapy at home, very well-tolerated. The next class of drugs are called monoclonal antibodies. On a cancerous cell, there is a marker. 

And so, we use monoclonal antibodies to be able to target the marker on the cancer cell. What that means is very specific. To that cancer cell, so, the most common target is the CD38, that’s a marker on one of the cancer cells. And we use a drug called daratumumab (Darzalex), that can be given as an IV or a subcutaneous agent, or another drug called isatuximab (Sarclisa). We also have other markers on the plasma cell. There’s a marker called SLAMF7, which we have other drugs called elotuzumab (Empliciti), which is often used for patients more in the relapse setting.  

Katherine:

Dr. Cottini, I’m wondering if you could briefly go over CAR T-cell therapy and bispecific antibodies. 

Dr. Cottini:

Yes, of course. So, these are all our new therapeutic approaches for patients. And these are types of treatments that are given to patients that already went through their induction, they went into remission, maybe they had a bone marrow transplant. And then, after a couple of years or months, unfortunately the disease came back, and they need the new and different treatment options. So, these two strategies, CAR T and bispecific antibodies, really rely on the T-cells, on the immune cells of the patient.  

And they all focus and target a specific marker on the plasma cells, but they work a little bit differently. So, the bispecific antibodies – and we have different antibodies.  

Some are approved by the FDA, some are just in clinical trials trials. They practically recognize something that is on the plasma cells, on the myeloma cells, that can be BCMA, GPRC5D, or other targets. So, at the same time that I am able to get close by the T cells, the immune cells, and in this way, practically there is both the antibodies and also the immune cells which is activating and getting rid of the cancer cells. 

So, these are infusions. Often, they’re done initially in the hospital and then in the outpatient setting. Sometimes it’s even every week, every other week or so.  

CAR T are different strategies, and it’s a very smart way of trying to get rid of the cancer cells. So, practically, these are T cells.  

So, these are immune cells from you, from the patient. And they are practically taken and then brought to a very specific and clean facilities where these T cells are modified in order to be able to recognize the cancer cells.  

And then these cancer cells are sent back to us and then practically they are given into the veins to patient, and then there is this kind of reaction of these T cells, which are very peppy and aggressive to be able to kill all the remaining cancer cells. So, these are all the new strategies. 

Obviously, we are kind of like in the early process, but these are very promising therapies I think we’ll be maybe moved up front even with diagnosis in the next 10, 20 years, we don’t know. 

Katherine:

I want to thank you both so much for your thoughtful responses. And as we close out the program, I’d like to get a final comment from each of you. What are you excited about in myeloma research, and why should patients be hopeful? Dr. Cottini?  

Dr. Cottini:

So, I think that especially if we look back especially at where myeloma was 20 or 30 years, I think we have made so many progresses, and there is really hope for our patients. I’m very passionate about research. That’s what I do. That’s why I read paper, I publish paper, and I think that it’s the heterogeneity of our disease is huge, and it’s difficult to tackle. But we as researchers, as physicians are the ones that can look at these changes, and find new therapies for our patients. So, I think that research is the way to go to be able to finally cure our patients. 

Katherine:

Dr. Rosko? 

Dr. Rosko:

Yeah, I mean I go Dr. Cottini’s sentiments. The multiplying therapies for myeloma really provides our ability to prescribe and make myeloma more of a chronic illness for our patients. I think it’s really important to allow patients to get really good targeted therapy personalized to them. Of course, we all are looking forward here to deep remissions. We want to be able to do that in such a way where we have good quality life for our patients. 

I think, importantly, as part of this program does here, we have to create access. So, most of myeloma is treated in the community, and most myeloma is diagnosed in older adults. And I really think how important it is, we talk about clinical trials, and being able to get our patients on to clinical trials, and to be able to get more knowledge about the disease process of pathogenesis, which I think is just really pivotal. 

So, I’m excited about personalizing therapy to the individual’s health and really being able to increase access to all of these novel therapies that we have. For patients, often at specialized cancer centers, but I’m really interested in how we can increase reach and access for all of these advances in myeloma research to every patient no matter where they’re at. 

Katherine:

Well, thank you both for joining us today. And thank you to all of our partners. 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.