Tag Archive for: Mount Sinai

What Are the Advantages of Seeking Care With a Lung Cancer Specialist?

What Are the Advantages of Seeking Care With a Lung Cancer Specialist? from Patient Empowerment Network on Vimeo.

What are the benefits of seeing a lung cancer specialist? Dr. Thomas Marron discusses the key advantages of specialty care, the value of a second opinion, and options for seeing a lung cancer specialist via telemedicine.

Dr. Thomas Marron is Director of the Early Phase Trials Unit at the Tisch Cancer Institute at Mount Sinai Hospital. Dr. Marron is also Professor of Medicine and Professor of Immunology and Immunotherapy at the Icahn School of Medicine at Mount Sinai. Learn more about Dr. Marron.

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Lung Cancer Treatment Plan Advice | Where Do Clinical Trials Fit In?

Lung Cancer Treatment Plan Advice | Where Do Clinical Trials Fit In?

Transcript:

Katherine Banwell:

What’s the advantage then of seeking care with a lung cancer specialist? 

Dr. Thomas Marron:

So, I think it’s extremely important. Unfortunately, a lot of the country, there are not lung cancer specialists available around the corner. But in large cities, there’s typically many lung cancer specialists, but I think it’s extremely important, at least as a second opinion, even if you’re not going to be treated locally by a lung cancer specialist, to seek out expertise.  

And often times, I’ll have patients that come from more rural areas outside of New York and they’ll come, and they’ll see me and then I’ll work with their local provider to come up with a treatment plan. Because the fact of the matter is, is that in every cancer type, but particularly in lung cancer, the field is moving so quickly. So, the treatment options that we have available today were not available in 2022.  

And we’re going to have probably five to 10 drugs that’re going  to be FDA-approved in the next year. And it’s typically the lung cancer specialist where it’s all that we do, we eat, breathe and live lung cancer, we’re the ones that really are up to date on everything. While if you’re seeing a general hematology, oncology provider who I’m always in awe of, they have to stay up to date on lung cancer, breast cancer, lymphoma, leukemia, everything under the sun.  

And when you have so much development in the research that’s happening, you really want to be talking to somebody, at least as a second opinion that knows exactly what the most latest data is and what the best options are available. And also, those lung cancer providers are usually the ones that will know exactly where you can go to get access to certain clinical trials.  

Katherine Banwell:

In seeking a second opinion, can somebody do a tele-visit, or do you have to actually, physically go to see the specialist? 

Dr. Thomas Marron:

So, it depends on the specialist that you’re trying to see.  

There are certain institutions that will allow you to do televisits. Oftentimes doctors, at least for their first encounter with a patient really want to see somebody in person, just so that we can really evaluate how functional somebody is. There’s a lot that I cannot tell through my computer screen, through my Zoom call with a patient.

And so, it can be a little bit difficult, but there are many centers, including our own that will offer patients televisits as a second opinion, for us to get a chance to talk to them about their medical history, review, the treatment decisions that they’ve had in the past or the current treatment decision that they’re dealing with and give our own opinion on what they should do.  

Lung Cancer Treatment Plan Advice | Where Do Clinical Trials Fit In?

Lung Cancer Treatment Plan Advice | Where Do Clinical Trials Fit In? from Patient Empowerment Network on Vimeo.

What questions should patients ask about a lung cancer treatment plan? Lung cancer expert Dr. Thomas Marron shares key considerations when choosing therapy and discusses where clinical trials fit into planning.

Dr. Thomas Marron is Director of the Early Phase Trials Unit at the Tisch Cancer Institute at Mount Sinai Hospital. Dr. Marron is also Professor of Medicine and Professor of Immunology and Immunotherapy at the Icahn School of Medicine at Mount Sinai. Learn more about Dr. Marron.

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What Are the Advantages of Seeking Care With a Lung Cancer Specialist?

What Are the Advantages of Seeking Care With a Lung Cancer Specialist?

Transcript:

Katherine Banwell:

What questions should patients be asking about their proposed treatment plan? 

Dr. Thomas Marron:

I think that in lung cancer, most patients are going  to get the same therapeutic approach offered to them wherever they go.  

It’s not like certain types of cancer where there’s 10 different ways to treat it. But there are some nuances and depending on the location in which you’re getting treated, whether it be in an academic hospital or a community setting, you may have different chemotherapies offered, immunotherapies offered. You may have different combinations offered. And so, I think it’s important to always ask your provider what other options are there, and why are they recommending one option over another. But I think it’s also really important that patients get second opinions.   

A lot of my patients, even my in-laws are always very skittish about getting a second opinion because they don’t want to insult their doctor, who they feel very close to. And I would say, it couldn’t be further from the truth. Any good doctor is 100 percent okay with a patient going and getting a second, third, fourth opinion because to us, the most important thing is that you have confidence in the decisions that we’re making about your treatment.

I always tell patients, I’m basically a waiter here offering you a menu of options and giving you my recommendation. But it is up to the patient in the end what treatment they receive and how long they receive it for.  

And if they decide ever to discontinue it. And I think that the more information, the more smart people looking at you, the better.  

Katherine Banwell:

Where do clinical trials fit into a non-small cell lung cancer treatment plan? 

Dr. Thomas Marron:

So, that’s a phenomenal question and one that I hope that everyone asks their providers when they see them because the reality is that while we are curing some patients, the vast majority of patients are not cured. And I think that all patients should at least consider a clinical trial, whether it be a first line clinical trial. So, the first medicine that you receive for your cancer, or at the time of progression.  

I think particularly, once patients progress on the first line therapy, those patients we really don’t have a cure for, even if we have some palliative chemotherapies or eventually these antibody drug conjugates to treat them.  

And so, I think everybody who is progressing on first line therapy should always consider a clinical trial. And I think it’s extremely important that patients realize the need to ask their providers about clinical trials, but also be an advocate for themselves and go out and get second opinions, get third opinions and see what trials are available in the community and even in other cities.

Because often times in New York City, I’ll have completely different clinical trials than my colleagues at the other five institutions in the city. And it’s really important that patients advocate for themselves, and they identify everything that’s available.   

Expert Perspective | New and Emerging Progress in Lung Cancer Treatment

Expert Perspective | New and Emerging Progress in Lung Cancer Treatment from Patient Empowerment Network on Vimeo.

What’s the latest in lung cancer research? Dr. Thomas Marron from the Tisch Cancer Institute at Mount Sinai Hospital discusses the advances in targeted therapy and immunotherapy and what this progress means for patients with lung cancer. 

Dr. Thomas Marron is Director of the Early Phase Trials Unit at the Tisch Cancer Institute at Mount Sinai Hospital. Dr. Marron is also Professor of Medicine and Professor of Immunology and Immunotherapy at the Icahn School of Medicine at Mount Sinai. Learn more about Dr. Marron.

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Lung Cancer Treatment Plan Advice | Where Do Clinical Trials Fit In?

Lung Cancer Treatment Plan Advice | Where Do Clinical Trials Fit In?

Transcript:

Katherine Banwell:

Dr. Marron, you’re a leading researcher in the field. What new and emerging progress in lung cancer care are you excited about? 

Dr. Thomas Marron:

So, there’s many extremely exciting, targeted therapies that’re in development. And so, as I mentioned, we do genetic sequencing, and we get three to 500 genes’ worth of data. But we only have drugs to target around 10 of those.  

So, hopefully in the coming years, in the next three to five years, we’ll have many more options based on somebody’s genetic profile of their tumor. I think that also, within the field of immunotherapy, which typically are given to patients who don’t have those targetable mutations. 

Immunotherapy is really, has revolutionized the treatment of lung cancer and with immunotherapy, we’re actually able to cure a subset of patients while in the past, we always said patients with metastatic disease had incurable disease, but it was treatable disease, just not curable.  

Now, we are curing a subset of patients. Unfortunately, we’re not curing the majority of patients. But the field of immunotherapy is evolving very quickly with new therapies targeting new parts of the immune system.  

So, similar with targeted therapies, it’s really an umbrella term. So, targeted therapy is an umbrella term for dozens of different drugs. Immunotherapy, similarly, is an umbrella term for dozens of different approaches to the immune system. So, dozens of different ways to turn on the immune system so that the immune system does its job and recognizes and kills cancer. Because your immune system is in your body to tell the difference between foreign things like COVID and normal things like your lung.  

And cancer is somewhere in between and there’s probably hundreds of different ways in which cancer finds an ability to hijack our immune system and then turn our immune system off. And so, I think with these emerging therapies that we’re developing now and will be further developed in the next five to 10 years, I think we’re going to see another revolution happen in the setting of immunotherapy.  

Katherine Banwell:

So, what do these advances mean for non-small cell lung cancer patients?  

Dr. Thomas Marron:

So, in non-small cell lung cancer, immunotherapy has really changed the way that we’re treating patients from 10 years ago when we were giving chemotherapy alone, or maybe 15 years ago. Ten or 15 years ago, when I saw a patient with metastatic disease, I would have to have a very frank conversation with them and tell them that the median survival was 10 months and that this was an incurable illness that would eventually take their life. Now, with the introduction of immunotherapy, patients are living more than twice as long on average. 

And there are a subset of patients, somewhere between 10 to 20  percent of people that go into remission and stay in remission. And so, that really has revolutionized the treatment. Obviously, we’re not done, because we still have to help the remainder of those patients and our goal is 100 percent cure. But the fact that we’re even using the C-word, cure in our cancer clinics is really amazing. 

Antibody Drug Conjugates for Lung Cancer | Advances in Research

Antibody Drug Conjugates for Lung Cancer | Advances in Research from Patient Empowerment Network on Vimeo.

What are antibody drug conjugates, and how are these new agents changing lung cancer care? Lung cancer expert Dr. Thomas Marron defines antibody drug conjugates and explains how they work to treat lung cancer.

Dr. Thomas Marron is Director of the Early Phase Trials Unit at the Tisch Cancer Institute at Mount Sinai Hospital. Dr. Marron is also Professor of Medicine and Professor of Immunology and Immunotherapy at the Icahn School of Medicine at Mount Sinai. Learn more about Dr. Marron.

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Transcript:

Katherine Banwell:

What are antibody drug conjugates, and how do they treat lung cancer?   

Dr. Thomas Marron:

So, antibodies are proteins that have been manufactured. They’re a synthetic version of something that happens in our own body And they’re very specific for a very unique protein. And so, there are certain cancer proteins, there’s proteins on the surface of cancer that really aren’t expressed anywhere else in your body. And so, what we can do is we can develop these antibodies that basically are a heat-seeking missile. So, you inject them like chemotherapy, through an IV. But they’re a heat-sinking missile, and they go throughout your body, and they stick themselves to the cancer.  

And hopefully, they don’t stick anywhere else. And basically, antibody drug conjugate means the drug is conjugated to the antibody, meaning you basically have glued chemotherapy onto that antibody.  

And so, what it allows us to do is, instead of giving chemotherapy through the IV like we normally would, where that chemotherapy goes everywhere in your body, and that’s the main reason that you have toxicity.  

It doesn’t just go to the cancer, it also goes to your bone marrow, to your hair, to your intestines, has side effects. Antibody drug conjugates, the goal of them is to really deliver the chemotherapy directly to the tumor and spare the rest of your body, the toxicity from the chemotherapy that’s glued onto the antibody.

It’s important to note that they still do have side effects. So, some of that chemotherapy, for lack of a better term falls off the antibody or it might leak out of the tumor after it kills the tumor cells. And so, there is still the potential for toxicity, very similar to the toxicities that we see with chemotherapy.   

But so far, the data is very encouraging, both in lung cancer and other cancer types that antibody drug conjugates might be a superior formulation of chemotherapy, so better able to treat lung cancer. And we have a few drugs that’re actually probably going to be FDA-approved in the second line setting for non-small cell lung cancer. So, that’s for patients who have received standard first-line therapy and unfortunately, their cancer has progressed.   

And we actually already have one drug that was, it’s called Enhertu that was developed for breast cancer. And that’s now FDA-approved for lung cancer, for a rare subset of lung cancer patients who have an exon-20 HER2 mutation.  

And the patients I’ve treated with that drug do extremely well, and so I think it’s a very encouraging sign of what’s to come using more and more of these targeted chemotherapy regimens.  

Katherine Banwell:

Yeah. Well, that leads me to the next question, is there a patient type that ADCs are right for? 

Dr. Thomas Marron:

So, maybe is the question, answer. So, I don’t know because we don’t have good biomarkers right now to identify the patients that’re going to respond best to the drugs that’re in development, at least those ones that’re furthest along in development.  

And we’re always searching for biomarkers, which basically just means a test that we do on the patient’s biopsy or in their blood to tell us who’s going to respond to a therapy and who’s not. Unfortunately, right now we don’t have a good biomarker for these drugs.  

Hopefully as we do larger trials and we study biopsies and blood from the patients on those trials, we can identify the subset of patients that will do best with the therapy. Because we always want to make sure we’re getting patients the best therapy for them and we’re avoiding giving these therapies, because there are some toxicities to patients that aren’t going to respond to the therapy. So, it’s definitely a work in progress. 

How Has Lung Cancer Molecular Testing Evolved?

How Has Lung Cancer Molecular Testing Evolved? from Patient Empowerment Network on Vimeo.

What are the latest advances in lung cancer testing? Dr. Thomas Marron discusses the role of molecular testing when choosing therapy and how innovations in technology have revolutionized lung cancer care.

Dr. Thomas Marron is Director of the Early Phase Trials Unit at the Tisch Cancer Institute at Mount Sinai Hospital. Dr. Marron is also Professor of Medicine and Professor of Immunology and Immunotherapy at the Icahn School of Medicine at Mount Sinai. Learn more about Dr. Marron.

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Transcript:

Katherine Banwell:

What should patients understand about the results of molecular testing? 

Dr. Thomas Marron:

So, molecular testing is extremely important and anybody who has metastatic non-small cell lung cancer should get it. And increasingly, with the new drug approvals, even patients that have earlier stage disease, stage II and III disease should also get molecular testing. Molecular testing is important to identify if there is a potential therapeutic target.  

But it’s also important to know that it may predict a response to a therapy, whether that be a targeted therapy or something like immunotherapy. But there is no guarantee. So, there’s no specific result from a molecular test that tells you there’s 100 percent chance you’re going to be cured by Drug X.  

And so, it’s important to always know that we’re following the data and we’re giving patients the drugs that, based on the knowledge we have today is the best option for them, based on their molecular test. But it isn’t a guarantee. And sometimes these drugs will work transiently.  

And so, they may work for weeks, months, year but then they might stop working. And it’s also important to understand that the mutational profile may change over time, which is one of the reasons why we do these genetic tests. Oftentimes multiple times. Not just at the time of diagnosis, but also when patients’ cancer starts to grow so that we can see if there’s a new molecular target that we might be able to identify and treat with a novel therapy.  

Katherine Banwell:

Dr. Marron, are there innovations in technology that are aiding in the advancement of lung cancer research?  

Dr. Thomas Marron:

Yeah, so there’s lots of developments in the molecular tests that we’re doing. One of them is that we’re able to track circulating tumor DNA. So, as cancer is growing, it grows in this very unorganized aberrant way, because the on and off growth switches within the cancer, within the DNA are very dysregulated. And what happens is that often times, they’re releasing a lot of cancer cells as they’re growing or also dying and releasing their DNA into the blood.  

And so, through blood tests, we’re now able to identify the mutations in a patient’s cancer. And this is a real revolution in the initial diagnosis of metastatic lung cancer because in the past, we had to wait for three, four, five weeks in order to know whether a patient had a targetable mutation like an EGFR mutation. Or if we should use a more agnostic approach, immunotherapy or chemotherapy to treat the patient.  

But now when I see a patient, typically I see lung cancer patients on Fridays, I will take some of their blood, I send it off for the liquid biopsy analysis. And by that following Friday, so just one week later, I typically have an answer of if the patient has a mutation that I can target, let’s say with an oral medicine or if they’re a patient that I should be treating with immunotherapy. Additionally, circulating tumor DNA, increasingly we can use it to identify or track a patient’s progress, as far as response to therapy.  

And so, this has really been developed in other tumor types, but increasingly we’re using it in lung cancer where we can either track how much cancer they have in their body. So, very early on, we can see if the cancer is shrinking or growing. And additionally, we can use it to detect patients after surgery, whether or not they have residual disease in their body.

And so, a lot of the times patients will undergo surgery because let’s say on a CAT scan, you might only see one large, isolated tumor. But after we take that tumor out, now we can do a blood test to see if there might be microscopic bits of that cancer that were left over, that we weren’t able to see on a CAT scan or PET scan.  

And it’s that patient population that we think benefits most from either chemotherapy or targeted therapy after surgery. So, we’re using circulating tumor DNA, both in the metastatic setting, where cancer has already spread to other parts of the body. And also, in the perioperative setting, around the time of surgery or radiation where we’re trying to cure patients. And we’re now able to use this technology to hopefully increase the likelihood that we’re curing them. 

Advances in Targeted Lung Cancer Treatments | What You Should Know

Advances in Targeted Lung Cancer Treatments | What You Should Know from Patient Empowerment Network on Vimeo.

Dr. Thomas Marron discusses how these therapies work to treat lung cancer, how the presence of certain mutations can impact care and treatment choices, and the research being done on new therapies to target specific lung cancer biomarkers.

Dr. Thomas Marron is Director of the Early Phase Trials Unit at the Tisch Cancer Institute at Mount Sinai Hospital. Dr. Marron is also Professor of Medicine and Professor of Immunology and Immunotherapy at the Icahn School of Medicine at Mount Sinai. Learn more about Dr. Marron.

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Antibody Drug Conjugates for Lung Cancer | Advances in Research

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Expert Perspective | New and Emerging Progress in Lung Cancer Treatment

Expert Perspective | New and Emerging Progress in Lung Cancer Treatment

Transcript:

Katherine Banwell:

Welcome, Dr. Marron. Would you introduce yourself, please? 

Dr. Thomas Marron:

Sure, I’m Tom Marron. I’m the Director of the Early Phase Trials Unit at the Tisch Cancer Institute at Mount Sinai Hospital. I’m a Professor of Medicine and also a Professor of Immunology and Immunotherapy at the Icahn School of Medicine at Mount Sinai. And I’m trained as both an oncologist and an immunologist.  

Katherine Banwell:

Excellent. Thanks for joining us today.  

Dr. Thomas Marron:

Thank you for having me.   

Katherine Banwell:

We know that the presence of certain mutations can affect lung cancer treatment options. Can you share the latest updates in targeted therapies?  

Dr. Thomas Marron:

Sure, so there’s been a lot of developments in targeted therapies as of late.  

Mutations in a patient’s cancer can represent a potential therapeutic target, and we have increasing numbers, every year we have new FDA approvals for typically pills that target very specific mutations and are able to either control cancer or even kill cancer. Additionally, we use DNA sequencing of tumors to identify mutations that could be predictive of a response to certain therapies. So, even though we don’t have a specific drug to target that mutation in their DNA, that change in their DNA that’s making the cancer grow, we do know that patients with certain DNA mutations do better on certain therapies than other therapies.  

And so, we can use mutations specifically to help guide therapy, even if we don’t have a targeted therapy for something like EGFR mutation or a KRAS mutation. And additionally, one of the things that we do as we’re treating patients is, often times we will give a patient with lung cancer a therapy and then their cancer may respond for weeks, months, even years.  

But then it might recur, or it might just start growing if it never went away entirely. And at that time, we’re oftentimes repeating the genetic sequencing, whether doing a biopsy or sometimes we can do what we call a liquid biopsy, which is just taking some blood and looking for some of the DNA from the cancer floating around in the blood.  

And the reason we do that is that if you see a change in the mutations, it might represent either a change in the type of cancer or it might represent what we call an escape mutation, or an escape mechanism where the cancer that had been responding to therapy X is now not responding because it changed its DNA to overcome the therapy you were given. And that might suggest that we try a specific new therapy, or that we just change our approach entirely.  

Katherine Banwell:

You’ve answered my next question to some degree, but I’m going to ask it anyway. How do these therapies work to treat lung cancer? 

Dr. Thomas Marron:

So, cancer is caused by changes in your DNA. So, your DNA is your instruction booklet on how cells should grow and when they should grow. And every cell in your body theoretically has the same DNA, except for, because of a variety of things like smoking or exposure to radon or just living in a large city full of pollution. As we get older, we basically accrue more and more mutations and changes in our DNA, our instruction booklet. And while most of these changes really don’t have any sequela, and they’re not going to affect the ability for the cancer, or for normal cells to grow.  

Sometimes you’ll get a mutation in a very specific gene that’s important for telling cells when to divide and when to grow and when not to grow. And you can think of it as a light switch where the light switch gets stuck in the on position and constantly, cells are growing and growing and growing and that’s when you have cancer. So, when you have these mutations, one of the approaches that we’ve been working on for the last few decades, in particular in the last few years.  

We have lots of these new drugs that target these mutations, and they basically turn that on signal off. So, they disrupt, it’s like turning the light switch off. You’re disrupting the constant grow, grow, grow signal and keeping the cancer from growing. Typically, we think of these targeted therapies that do this, not as cures for cancer, at least when patients have metastatic disease, but they’re very good at controlling cancer. And some of these therapies can work for years, even a decade and control the cancer. But often times, unfortunately cancer always finds a way to outsmart us, even when we’re outsmarting it.  

Katherine Banwell:

Right. Are there new mutations being discovered that can impact the future of small cell lung cancer care? 

Dr. Thomas Marron:

Well, I’m not sure I would say that there’s a lot of new mutations that’ve been discovered, per se. Every time that you come in and get a diagnosis of lung cancer, we typically will take the tissue and like I said, sometimes we’ll take some blood and do a liquid biopsy and look for a slew of different known mutations.   

And typically, we’ll look for anywhere from three to 500 known mutations in the cancer, even though we only have drugs to treat about 10 of those three to 500. The nice thing though is that as we learn more and more and more about these mutations and we study them, we are developing more and more drugs to address specific mutations. So, five years ago we really only had three different mutations that we could target.  

Now, we have around 10 because we have all these new drugs that target very specific mutations whether they be in genes like MET or RET or KRAS or BRAS.  

So, I think that while we aren’t necessarily discovering that many new genes, we’ve been looking at the genetic sequence of cancer and also, just the human genome for 20 to 30 years at this point, we’re discovering lots of new drugs that can target those specific mutations that we know patients have, but that most of the mutations we identify are not necessarily druggable targets.  

Expert Advice for Patients With Small Cell Lung Cancer

Expert Advice for Patients With Small Cell Lung Cancer from Patient Empowerment Network on Vimeo.

Dr. Triparna Sen, a leading small cell lung cancer (SCLC) researcher and expert, shares key advice for patients. Dr. Sen stresses the importance of working closely with your doctor, asking about clinical trials options, and the benefits of support groups.

Dr. Triparna Sen is an associate professor in the department of oncological sciences and co-director of the Lung Cancer PDX Platform at the Icahn School of Medicine at Mount Sinai in New York. Learn more about Dr. Sen.

See More from Thrive Small Cell Lung Cancer

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Advances in Small Cell Lung Cancer Research | Hope for the Future

Understanding Small Cell Lung Cancer Treatment Options

Understanding Small Cell Lung Cancer Treatment Options

Transcript:

Katherine:

What three key pieces of advice would you have for a patient who has just been diagnosed with small cell lung cancer?  

Dr. Sen:

First of all, I would like to say definitely, definitely work with your physician. They are trying to do their best for you. Work with your physician. Follow the treatment regimen that they give. Ask about clinical trials that you are eligible for and that you can enroll into. Then, of course, having a support group. So, there are many patient advocacy groups right now for non-small cell and small cell lung cancer.  

I think being a part of such a patient advocacy group where you have people going through the same journey, I think, it really helps. It helps you sort of manage your disease better. It helps you stay hopeful when you hear about other people’s sort of prognosis and if they have durable benefits from drugs. So, I think having a support group is very important. If there is an ability for you to contribute to research in terms of giving blood or tissues, if your physician is saying that you could be eligible for that, I think a contribution to research is really key. 

Because looking at the disease mechanisms in the clinical tissue is sort of where for us it is absolutely golden. We go there. We look at the disease mechanisms and tissues. If there is an opportunity for you, then I think it should definitely be explored.  

Finally, I would like to say we are really trying as researchers to really understand the disease better. We’re trying to do that better. I hope and I pray that we go faster with it. But I think there is hope right now for patients with small cell lung cancer. The research is really progressing better. There are many clinical trials.  

So, I think stay hopeful and have a peer support group who can take you through this quite difficult journey.  

Katherine:

Why should patients consider consulting with a lung cancer specialist?  

Dr. Sen:

I think it’s crucial because these lung cancer specialists really know the current state of the art treatments. They are thought leaders. They participate in trials. They actually sit on advisory boards with companies.  

They are strategizing the entire treatment landscape for this disease. So, if you go to a lung cancer specialist, you’re more likely to get the most updated knowledge about what treatments are out there, what you qualify for, what are the clinical trials out there, and what are working in patients. This is not just for small cell. There are many, many trials that are happening in non-small cell also. So, whatever your diagnosis is, a specialist should be able to tell you what your options are. You really want to know about your options. Your options about biomarker testing.   

Your options about screening. Your options about trials. I think a lung cancer specialist can really guide you towards that.   

Katherine:

Dr. Sen, thank you so much for joining us today. It’s been a pleasure speaking with you.  

Dr. Sen:

Thank you.  

Advances in Small Cell Lung Cancer Research | Hope for the Future

Advances in Small Cell Lung Cancer Research | Hope for the Future from Patient Empowerment Network on Vimeo.

What new treatments are being studied for small cell lung cancer (SCLC)? Dr. Triparna Sen, a leading researcher in the field, shares promising updates, including advances being made with LSD1 inhibitors, DDR (DNA Damage Response) inhibitors, and DLL-3 targeted therapies.

Dr. Triparna Sen is an associate professor in the department of oncological sciences and co-director of the Lung Cancer PDX Platform at the Icahn School of Medicine at Mount Sinai in New York. Learn more about Dr. Sen.

See More from Thrive Small Cell Lung Cancer

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Essential Small Cell Lung Cancer Testing

Essential Small Cell Lung Cancer Testing 

Expert Advice for Patients With Small Cell Lung Cancer

Expert Advice for Patients With Small Cell Lung Cancer

Understanding Small Cell Lung Cancer Treatment Options

Understanding Small Cell Lung Cancer Treatment Options

Transcript:

Katherine:

Dr. Sen, you are a leading researcher in the field. What is the latest research news that you can share with us about small cell lung cancer?

Dr. Sen:

There’s a lot of great research going on in my lab and labs all across the world. I think for the first time in a very long time, we are really trying to dissect the biology of small cell.   

It has been a research in making for many years. I think we have now really come to a point where we are really trying to understand the disease. I’ll go into a little more about the questions you are trying to answer. So, one of the main questions or one  of the main things that kind of is a hurdle to getting durable treatment options is that the frontline chemotherapy and immunotherapy doesn’t work as well as they should even for the approved regimens, which is the chemotherapy and the immunotherapy.  

The patients often do not have durable benefits. Even if patients have durable benefits, it’s only in a very minority of patient population which means in only about 10 to 15 percent of the total patient population actually do have any benefit from the frontline treatment. So, the main question that we are trying to answer is that why do these patients not respond to immunotherapy and chemotherapy in the frontline.  

What are the mechanisms of resistance to chemotherapy and immunotherapy? Primary resistance, what I mean by primary resistance is that patients who never respond. The disease comes back even while they’re getting the frontline chemo. So, the primary resistance, the mechanisms. Of course, when they have acquired resistance after the maintenance regimen when they come back, why are these patients having this acquired resistance to chemotherapy and immunotherapy? Because only when we understand resistance mechanisms will we be able to then come to the combination strategies.

That’s the next area of research is that once we understand the mechanism of chemotherapy and immunotherapy resistance is then coming up with effective combination therapy. So, what should we combine with immunotherapy in order to make immunotherapy better? I’ll give you an example from the research that we did. 

So, our lab focus is, as I said, on making immunotherapy better. What we understood is that there are certain epigenetic modifiers like LSD1.  

Repressing these, repressing LSD1, with a small molecule inhibitor actually augments or benefits the response to immunotherapy. So now, we are looking at LSD1 inhibitors in combination with immunotherapy. That’s one area that we are focusing on. The second are that we published extensively on is DNA damage response inhibitors which really works in combination with immunotherapy and makes immunotherapy response better.  

Now, we are investigating that in the lab the combination strategies of combining these DNA damage response inhibitors with immunotherapy. So, combination strategies. I think always coming up with novel targets. I will mention there are many novel targets that are right now in the clinical trials actually showing really, really encouraging data.  

I’m talking about DLL3 targeted BiTEs or ADCs we have seen that are showing preliminary data. We have seen a really good really good response in patients. So, finding these targets that are very specific for small cell and that can work in these unique population of patients.  

So, DLL3 targeted agents. There are agents that target B7-H3. So, we are looking at these novel targets and where they could fit in the current therapeutic regimen. Finally, since small cell lung cancer is not a surgical disease, we have to look for other options to find biomarkers. So, liquid biopsy. Liquid biopsy, what I mean by that is understanding the disease not just from tissue but also from blood.  

There’s a lot of research that’s happening in understanding the biology of small cell from blood draws from these patients.  

So, the field of using liquid biopsy or understanding the disease from blood draws is one of the areas that many labs, including ours, are focusing on, and how we can utilize these blood samples to then monitor the disease and also understand the resistance mechanisms to various drugs. I think these are the areas that we are investigating and seems, to me, very important areas that we need to address in order to really manage small cell lung cancer.   

Katherine:

What do these advances mean for small cell lung cancer patients? Are you hopeful?  

Dr. Sen:

Oh, yes. Of course. We’re always hopeful. That’s the goal, right. The goal is to have effective therapies that work and that works for a long time. That also benefits the patients in terms of quality of life which means without very severe adverse effects.   

So, very hopeful. Because I think what was limiting us for all those years for the last 40 to 50 years is that we really did not understand the complexity of small cell lung cancer. It is a very complex disease. It is very different from non-small cell lung cancer which has these mutations that you can target drugs against. So, there are this EGFR mutations and KRAS mutations in non-small cell.  

But small cell, it’s not that. It is not a disease where we have these GATA function mutations that we can devise therapies against. It’s a very different disease. The disease is aggressive. The disease progresses fast, and it also changes its physiology very fast. So, I think for the first time, we really are trying to understand the biology. What that helps is then to come with very informed decisions about therapy.  

So, yeah, I’m very hopeful. Because I think we have now targets that we are actually seeing benefits in patients. I think the more and more we understand resistance mechanisms, we’ll also be able to manage that better.   

Katherine:

That’s very promising news. 

Understanding Small Cell Lung Cancer Treatment Options

Understanding Small Cell Lung Cancer Treatment Options from Patient Empowerment Network on Vimeo.

How is small cell lung cancer (SCLC) treated? Dr. Triparna Sen discusses treatment options for patients with small cell lung cancer, both first-line and second-line therapies, and the important role of clinical trials in patient care. 

Dr. Triparna Sen is an associate professor in the department of oncological sciences and co-director of the Lung Cancer PDX Platform at the Icahn School of Medicine at Mount Sinai in New York. Learn more about Dr. Sen.

See More from Thrive Small Cell Lung Cancer

Related Resources:

Essential Small Cell Lung Cancer Testing

Essential Small Cell Lung Cancer Testing 

Expert Advice for Patients With Small Cell Lung Cancer

Expert Advice for Patients With Small Cell Lung Cancer

Advances in Small Cell Lung Cancer Research | Hope for the Future

Advances in Small Cell Lung Cancer Research | Hope for the Future

Transcript:

Katherine:

How do test results impact care? 

Dr. Sen:

So, you know, once the doctor has confirmed the small cell lung cancer and we have confirmed what stage it is at – what I mean by staging is that it could be either a limited stage disease which is an early stage small cell, or it could be an extensive stage of small cell. The treatment for those two are quite different. So, if it is an early stage or limited stage, patients are usually treated with chemoradiation. If it is an extensive stage or a metastatic small cell, then patients are usually given a standard of care which is chemotherapy in culmination with immunotherapy which is an antibody against PD-L1.  

Katherine:

You’re talking about treatment options that are currently available for small cell lung cancer. What about targeted therapies?  

Dr. Sen:

There aren’t very many therapeutic strategies that are targeted therapies as we speak like we hear from non-small cell lung cancer.  

So currently, like I mentioned, the frontline treatment for small cell lung cancer is with chemotherapy and immunotherapy and maintenance with immunotherapy alone.  

Once the patient relapses, which often is the case – all patients actually have resistance to the frontline chemo-io (chemoimmunotherapy) at some point in time. Once they have a relapse disease, the second line of therapy until now is with either topotecan or irinotecan which are two topoisomerase inhibitors or with lurbinectedin which is in the second line.  

So, when it comes to targeted therapies, so far we a have seen, you know, the conventional way that we think about EGFR inhibitors or KRAS inhibitors, it hasn’t been the case so far with small cell lung cancer. It’s very limited in the current approved setting. But there are many clinical trials that are investigating several targeted therapies that are either targeting – I can speak about that more as I talk about research strategy. But there are many targeted agents that are targeting surface targets like DLL3, B7-H3, or SEZ6. There are other targets that are targeting things like DNA damage repair, proteins, or epigenetic regulators like LSD1. But so far in the approved setting, it is quite limited.  

Katherine:

When we look at what therapies are available, what treatment options are available, what are some typical side effects? How are they managed?  

Dr. Sen:

Some of the major side effects that you see, especially with a frontline chemo-io (chemoimmunotherapy), are very common like you see with other cancer types. Also, it’s usually myelosuppression.  

I think it is prevented or is managed either by dose reduction or treatment delays or treated with transfusion. There has been research that CDK4/6 inhibitors, trilaciclib, when treated with in combination with chemotherapy can bring down the side effects that we see with chemotherapy.  

Some of the immunotherapy related adverse events includes pneumonitis, colitis. They are usually treated with early steroids, treatment withholding, and also it could be leading to permanent discontinuation of the treatment if the adverse events are really severe. Those are mainly what we see we the chemo-io (chemoimmunotherapy) regimen that is given up front.  

Katherine:

Okay. What questions should someone be asking about their proposed treatment plan?  

Dr. Sen:

Right. So, I think, of course, first is what stage. The treatment will depend upon the stage of small cell. Usually, on the frontline, everyone is given chemotherapy and immunotherapy. 

It’s a systemic therapy that’s being given. But I think the patient should be asking questions like are there clinical trials available for me. Because there are multiple clinical trials right now in the frontline and the second line setting.  

So, I think definitely the patient should ask about the clinical trials that the qualify for. In terms of contributing to research, I think if there are options for them to either sign up for blood collection protocol or for tissue collection protocol, I think the patient should definitely enroll for that.   

Because that really helps our research strategy. But in terms of treatment, I think they should ask about available clinical trials that they qualify for.  

Katherine:

Let’s turn to clinical trials then. Patient participation, of course, is essential to finding new and better treatments. What would you say to someone who’s hesitant to participate in a clinical trial?  

Dr. Sen:

Yes. I mean, that’s often the thing. We hear about these novel drugs. They’re in trial. For a disease that’s that aggressive, I think once there is a relapse, I think clinical trials could be a very good option for patients. These are novel drugs that have come out of very robust research that we do in the lab. They can often work quite a bit. So, I think, of course, talk to your physicians. Talk to them at length about whether you do qualify for it. But if there is a trial at the center that you’re getting treated at and if the doctor advises that, I think enrolling in a clinical trial could be a very good option for patients, especially in the aggressive setting where there are not many options available for patients.  

As I mentioned here, research is my true north. I mean, all my lab does is understanding the biology of small cell. It’s extremely essential that we actually try to get the knowledge of the patient tumor. So, if you have availability of contributing either in terms of tissue or blood to research, I think I would advise and encourage patients to definitely contribute to that. 

Essential Small Cell Lung Cancer Testing

Essential Small Cell Lung Cancer Testing from Patient Empowerment Network on Vimeo.

What tests are essential for patients with small cell lung cancer (SCLC)? Dr. Triparna Sen defines small cell lung cancer and reviews the testing that should take place following a diagnosis.

Dr. Triparna Sen is an associate professor in the department of oncological sciences and co-director of the Lung Cancer PDX Platform at the Icahn School of Medicine at Mount Sinai in New York. Learn more about Dr. Sen.

See More from Thrive Small Cell Lung Cancer

Related Resources:

Understanding Small Cell Lung Cancer Treatment Options

Understanding Small Cell Lung Cancer Treatment Options

Expert Advice for Patients With Small Cell Lung Cancer

Expert Advice for Patients With Small Cell Lung Cancer

Advances in Small Cell Lung Cancer Research | Hope for the Future

Advances in Small Cell Lung Cancer Research | Hope for the Future

Transcript:

Dr. Sen:

I’m Dr. Triparna Sen. I’m an associate professor at the Icahn School of Medicine. I’m also the co-director of the Lung Cancer PDX program here at the Icahn School of Medicine at Mount Sinai, New York. I am the lead of a very translational research laboratory. Our goal is to find novel and effective therapeutic strategies for patients with lung cancer.  

Katherine:

Thank you for that. We’re so glad to have you with us today. Would you define small cell lung cancer for our audience?  

Dr. Sen:

Of course. So, one of the main research areas in my lab is to try to understand the biology of this very aggressive form of lung cancer. Having said that, as you all may be aware that lung cancer is one of the leading causes of cancer related mortality.  

Lung cancer can be of two types, non-small cell and small cell. So, small cell is a very high-grade neuroendocrine tumor. And it is a very aggressive tumor.   

The name is derived because the size of the cells that you see under the microscope is very small. So, it was originally called old cell carcinoma, and now it is called small cell lung cancer. What you need to remember about this disease is that it is about 15 percent of lung cancer diagnosis. It is very highly metastatic. It is often associated with a long history of smoking.   

Katherine:

Okay. What testing should take place following a diagnosis of small cell lung cancer?  

Dr. Sen:

The symptoms can include various things like coughing, labored breathing, or even bleeding during coughing. What happens then is the initial diagnosis actually happens through some sort of contrast enhanced CT or PET CT. Also, a confirmatory test that happens through immunohistochemistry with H&E. That is  how we look at the histopathological features of the cancer. So once it is confirmed to be small cell lung cancer, then additional tests may happen through tumor biopsy where the doctor then confirms the stage of the tumor and how much the disease has spread.  

 So, there may be biopsies taken from the lung and from other regions of the body to determine how much the disease has spread.  

How Can I Get the Best Lung Cancer Care?

How Can I Get the Best Lung Cancer Care? from Patient Empowerment Network on Vimeo.

How can lung cancer patients access optimal care? Expert Dr. Christian Rolfo from Mount Sinai and Dr. Nicole Rochester discuss the latest lung cancer treatments and research, lung cancer testing, equitable care, and patient-centered care for the best health outcomes.

See More from Best Lung Cancer Care

Related Resource:

Lung Cancer Treatment Landscape Overview

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What Are the Latest Lung Cancer Treatment Updates?


Transcript:

Dr. Nicole Rochester: 

Hello and welcome. I’m Dr. Nicole Rochester, I’m a pediatrician, a professional health advocate, and your host for today’s Patient Empowerment Network program. We are so happy that you tuned in. How can you access the best possible lung cancer care? What do the latest combination therapies mean for you? Should you consider a clinical trial as a path to enhancing your lung cancer care? This Best Lung Cancer Care program focuses on providing actionable steps to achieving equitable care and connecting to patient-centered care on your path to empowerment. We are joined today by international lung cancer expert, Dr. Christian Rolfo, Professor of Medicine and Associate Director for Clinical Research in the Center for Thoracic Oncology at the Tisch Cancer Institute. Thank you so much for joining us today, Dr. Rolfo.

Dr. Christian Rolfo: 

Thank you, Dr. Rochester, for having me. It’s a pleasure to be here. 

Dr. Nicole Rochester: 

Wonderful. I’m looking forward to our conversation. Now, following this program, you will receive a survey and we would be thrilled to get your feedback because this helps inform future lung cancer programs we produce. Please remember that this program is not a substitute for seeking medical care, so please be sure to connect with your healthcare team regarding the best options for your care. Now, let’s delve into this very important topic, how can I get the best lung cancer care? And, Dr. Rolfo, we’re going to start with an overview of the lung cancer treatment landscape. We know that this landscape is rapidly changing and keeping up with the pace of developments could be a challenge not only for doctors, but certainly for patients and family members, so I was hoping that you could give us an overview of the current lung cancer treatment landscape.

Dr. Christian Rolfo:

In the last year, lung cancer treatment was changing radically. We have actually, including some of their new concepts as precision medicine or personalized medicine, that we have actually different therapies that are specifically for some group of patients, that they have specific alterations in their tumors. And when I’m talking about alterations I refer to mutations, genomic alterations that can be targeted nowadays with specific medications, and currently, some of them are actually, the majority of them are actually pills, for example. So it was changing radically and we are not using it like before chemotherapy for everyone. Another area of important interest was the introduction of immunotherapy, this is also an important tool for fighting cancer, and there you have a substance that are administered generally, all of them are intravenous, and this is the principle of that is to await from your own inner system, from the patient immune system, they are the tools to fight against the cancer, so it’s a very innovative way to approach cancer, and this is.

The good thing is that these two approaches targeted therapies, immunotherapy, and also still obviously the combination with chemotherapy in some of the case with immunotherapy, we can use not only metastatic patients, so in patients who have advanced disease, but also we can use in patients who have earlier stage that they were operated, for example, and we want to prevent that this patient is not going to a further process of cancer metastases, or there are several, several innovations. Then we have innovations that are coming also from local treatments and we call local treatments the one that, for example, surgery or radiation, we have new technologies also that are arriving there, and the combination sometimes with the medical treatment or systemic treatments that are going everywhere that is the description of systemic are helping these patients to have not recurrence and improving. Actually, lung cancer survival was really improving in the last years, and we are very excited by that because, unfortunately, it’s very still an aggressive disease that we were able to change with all this armamentarium the prognosis of these patients.

Dr. Nicole Rochester:

Wow, that’s a lot. I mean it’s exciting to hear that there are so many new developments on the horizon and that so much has happened just in the last year as it relates to therapy. What have we learned about drug resistance as it relates to non-small cell lung cancer? Are there any new developments in that area?

Dr. Christian Rolfo:

Yeah, obviously the patients of the…as I just commented, we have different patients with different needs and different scenarios, so we are now fragmenting a lot of the diseases and we have actually different diseases, and one big disease that is the lung cancer, so now we are treating patients in a different way. And some patients have, for example, patients who are under treatment with targeted therapies, they can develop mechanics of resistance that we can nowadays not only identify but also treat. 

So we can treat and change the recurrence of these patients. One of the tools that we are using for that is liquid biopsy, for example, that is this blood draw that we are going for the patients, and actually, we are trying to do this determination from the very beginning and also monitoring the patients after we have this information to see if we are able to determine the mechanics of resistance, see also the outcomes of some of the therapies and change the treatment when it’s necessary. In immunotherapy, we have alterations that are resistant or refractory, that is another way of definitions so refractory we say patients that are not responding during the treatment and resistance of patients that or simply patients that are after the treatment having a progression in a very short time, so we need to identify these two categories and try to treat them in different ways that we have armamentarium for that as well.

Dr. Nicole Rochester:

Wonderful, thank you for that. So you’ve mentioned a lot about updates, are there any other exciting updates that patients and families should know about related to lung cancer, maybe things that are in the works that we may hear about in 2023?

Dr. Christian Rolfo:

Yeah, I said, for example, liquid biopsy I was mentioning liquid biopsy, and we are focused obviously, and in patients that have advanced disease or when they have this disease that is already confirmed. But we are now moving the tools that we have to the dedication of cancer using liquid biopsy from the very beginning, so we can use a minimal residual disease that is patients after the surgery. And I think I hear answering one of the questions that we have in the chat that this minimal residual disease is the quantity of two more that sometimes we are not able to see in the images or is very tiny, and we have equivocal information, the possibility to discover the patients that after surgery, have the possibility to recurrence or have come back of the disease is really important. 

And also we are looking for early detection of lung cancer trying to identify patients with the high-risk populations that they are maybe having the opportunity to be in lung cancer screening because they are smokers, or because they have all the characteristics on top of this model that we can also use the liquid biopsy there. But one of the most important messages that I want to say, because I mentioned it here smokers and I want to remind you that we have a big proportion of patients around 20 to 25 percent of the patients that they never smoked and that they can develop lung cancer, so we have a motto, we say if you have a lung, you can have it because we want to break this stigma that lung cancer has the only patients who are smoking, obviously, smoking and tobacco are related highly with lung cancer. 

Dr. Christian Rolfo:

But also we have patients that are second-hand smokers or they have other causes of lung cancer, so we need to be aware and we need to try to get attention for that because, in this special population of non-smokers, we know that there is a special characteristic that we can treat them completely different, so it’s very important that we identify those patients as well.

Dr. Nicole Rochester:

I really appreciate you sharing that, Dr. Rolfo, because as I’m sure you know, there’s a lot of stigma associated with lung cancer and the assumption that if you have lung cancer, then that automatically means that you are a smoker, and not that we know that people who smoke, those are challenges, but to just acknowledge that not everybody with lung cancer is someone who is a smoker, and also that the approach, the treatment approach may be different, so I really appreciate you pointing that out.

Dr. Christian Rolfo:

And actually Dr. Rochester, you know this stigma was causing several domino effects. We have less funding for research, we have less support from the community sometimes like other tumors have, for example, breast cancer. So if we are looking specifically in lung cancer, the quantity of women that are dying or are going to a diagnosis of lung cancer, it’s very impressive, but actually it’s killing more people sometimes than other tumors. So we need to be very careful with this stigma because we need…and this is a call for action, now we need more funds, we need more support from the community, because this is a very important area that will need research.

Dr. Nicole Rochester:

Absolutely, so that brings me to the next section of our program, you’ve mentioned a lot of these therapies already, I just want to go a little bit deeper into exploring some of the lung cancer treatment strategies and also talk about clinical trials, so you talked about bio-markers. Can you expand a little bit on that? We know that no two lung cancers are the same. Can you explain to the audience how biomarkers help with lung cancer treatment and they can be so important? 

Dr. Christian Rolfo:

Yeah, we have different…as I say, we are looking at specific characteristics from the tumor when I’m referring to genomic alterations that I’m not referring to something that you can get from your family and bring to your descendants. So I’m talking about mutations that are occurring inside the tumors and only for the tumor, and so affecting only the subject that have this patient that has this alteration. So these biomarkers are an important way to identify populations that we can treat specifically, and I would like to be a little bit more specific on that. We have some of the alterations, for example, one of the mutations that we call EGFR or epidermal growth factor receptor mutation that is supported in different populations in different frequencies. 

For example, if we have patients that are with an Asiatic origin, we have there the possibility to have a…and I’m referring, for example, Chinese, Japanese, this area of the East Asia, we have a hyper-prevalence of these mutations in around 50 percent of the patients with lung cancer, non-squamous we’d say this is another characteristic of the tumor can have this specific alteration. If we are moving, for example, to Latinos, the pains of the areas of Latinos they are coming from, if you have Mexican or for example, Peruvian, they have also due to their ancestry, they are similar to the Asiatic population, 40 percent we’re going to white populations and Anglo-Saxons or Europeans, they have around 7 to 15 percent according to the different regions. 

African-Americans within 15 to 20 percent. So these kinds of alterations are giving us the opportunity to treat and we have nowadays inhibitors and that’s drugs that are from first, second and third generation, so we were evolving in January, this pharmaceutical in January to develop all drugs that are able to penetrate in the brain and acting not only in the tumor, but also in brain metastases. And patients who have this mutation, for example, are treated in first line, in front line, or the first treatment that they receive are pills, no chemotherapy. 

So for this reason, and that is something that is important because when we know that patients, when they start this journey of lung cancer diagnosis before they see an oncologist, they were struggling to get the diagnosis and then we’re passing through several doctors from the general practitioner or to the emergency room, going to CT scan and then a biopsy then a pulmonologist until they get the diagnosis, it’s a big period of time sometimes that we are very nervous because we want to each patient to have a treatment as soon as possible, and sometimes when they arrive to us, we say they need to wait until we have the results of these biomarkers.

So it’s difficult to understand, I put in the place of the patients and the families are really difficult to understand that I was passing a lot, I went here, I came here and I want your treatment right away, but this period that we are asking to wait is really important because we will have information that can change radically the treatment and the history of these patients. So one of the problems that we have in America is the lack of testing, so we have all the tools to test the patients, but if we are looking at some of the statistics, 50 percent of the patients have been tested…39 percent if we are moving to groups, for example, of African-Americans, so we need to be very careful that don’t push to get the treatment very quickly without having all the elements to this thing, which kind of treatment is the most adequate for the patient. 

Dr. Nicole Rochester:

That is such important information, and I really appreciate that, I appreciate it. That you put it in the perspective of the patients and family members. And that grueling, long wait, long time to diagnose this, and finally you’re in front of a specialist and the perception is that, Okay, now I’m going to get this treatment that I need, and then like you said to hear, now you have to wait a little bit longer, but also to understand that that wait is important to make sure that you get the treatment that is meant for your specific type of cancer, I think that is so incredibly important.

Dr. Christian Rolfo:

And believe me, we are trying to push as well from the that there are unfortunately technical times that we cannot overcome that are for testing and for having these results, and we can do that by like I said liquid biopsy, but also tissue biopsy, so we are sending the tissue that the patients gave for a biopsy in a biopsy or in a resection when they have surgery. We take these small biopsies and we send them for analysis and take longer sometimes, so it’s a pity, and we know but it’s the only way to go for the right treatment.

Dr. Nicole Rochester: 

So with regard to the biomarkers, you mentioned that these are kind of unevenly distributed among different populations depending on your origin, and so how does that play into the progression of the disease, what do we know about why patients with specific biomarkers have a different degree of disease progression?

Dr. Christian Rolfo: 

Yeah, so we know more or less that the characteristics, I mean more or less in terms of the evolution of the clinical characteristics of these patients, in terms of organ affection in case of progression, but what is most important of this is that we are able to continue to identify, and I say monitoring these patients with liquid biopsy for example, this is a good tool to understand or to understand it a bit better, which kind of mechanistic involvement. So because we have, for example, patients who were receiving the case that I was discussing before EGFR mutations and they received one graft from the very beginning, a third generation TKI is the one that is approved for the first line, and this patient has a progression.

 The possibility to have a mechanism of resistance is different, so we can have mutations that are coming in the same pathway, so in the same area, same kind of mutation, but different location, just to the people understand is the kind of line and we have the mutation that is here, the one that we are attacking, but we have another mutation that is in this area and it’s not covered by the track that is covering this mutation. 

Dr. Christian Rolfo: 

So we have nowadays drugs that are going to, in this area in clinical trials, or we have in other cases other areas of the task of mutations that have nothing to do with the original one. So we are activating another kind of pathway, or we are transforming the tumor from one kind of tumor to another kind of tumor, so for this reason, identify which kind of mechanism of resistance is in place can have an important or have important implications for how we are treating these patients, so we need to look at that to treat the patients.

Dr. Nicole Rochester: 

Wonderful. And speaking of resistance, we know that there are some patients who end up trying multiple therapies in order to treat their lung cancer, are there alternative treatment strategies for lung cancer patients who have failed all therapies? 

Dr. Christian Rolfo: 

Yeah, absolutely, we have research in lung cancer is never stopping in oncology generally, but in lung cancer it’s really exciting to see how this research is evolving and it’s arriving to the patients the meaning of the research when we are doing access to the patients, to the discovery of the finding that we have, and obviously, we have strategies in the clinical practice, but also we have the clinical trials. So clinical trials, and that is something we need to try to define very well because some patients believe that when we are going to clinical trials there are no more options or we don’t have any other options to do. We are sometimes using clinical trials even in the first line, so even in patients that are for the first time being treated. 

Because we know that some of the cases we are treating patients with from some standard of care and using drugs on top, we want to explore it, we can improve these outcomes that we already know. That could be also a clinical trial, that is also a clinical trial. So don’t take the participation in a clinical trial as the last option that you have, sometimes you will go to your doctor and the first time that you see a doctor for your first diagnosis, they can propose a clinical trial. 

And this is really valuable. What we really appreciate is the collaboration of the patients to be in clinical trials, because we need to remember that the drugs that we are using today were analyzing other patients before, so the treatment that you are receiving in a standard of care today were before a clinical trial, it’s really important how we can interact with the research and the clinical practice very easily, so we have also some options that are…for what we call early drug development, that there are some drugs that are in patients who are receiving the standard of care, and they have the opportunity to be treated in new drugs, and you can discuss…believe me there, and 

I know that there is a lot of questions about clinical trials but the clinical trial setting is really restrictive, it’s very well-coordinated, so you would be part of a very coordinated and structured things that they try to protect the patients in the first instance, and try to understand also how we can help the patients and the future generations. So that is really why we appreciate patients, that the contribution of patients that are giving to this clinical research because it’s helping to advance the knowledge for the new patients as well.

Dr. Nicole Rochester: 

And I really appreciate how you described clinical trials, and particularly your distinction about it’s not always this last-ditch effort that sometimes you all are using clinical trials as first line therapy. One of the common things is that clinical trials are tomorrow’s medicine today, and helping patients and families to understand that there’s value in being involved in clinical trials and that…and I think with COVID there’s a little more understanding, but certainly, we have a long way to go, and so I appreciate you sharing that. Do you have any specific examples of patients in your practice, and not names of course, but examples of…that have benefited from clinical trials?

Dr. Christian Rolfo: 

Absolutely, we have several of examples and actually FDA was doing a terrific job in the last year to try to get access quickly access to the drugs for patients, and some of this access that was granted was based in clinical trials that we’re starting for a phase one or phase two trials, so we are really doing a very rapid evolution of the drug development, and this is a revolution actually of the drug development because we have access very quickly. I can tell you that it was certainly in my career, several patients in clinical trials that they got benefits. Obviously, clinical trials are answering questions, so that is the way that we can answer questions scientifically and is the only way that we can advance in clinical therapeutics. 

Dr. Nicole Rochester: 

Wonderful. So I want to move into treatment access, we’ve talked a little bit today about some of the differences that we see in lung cancer with regard to the biomarkers, you and I know, and I’m sure that was in the audience, know that health disparities are widely reported here in the United States with really any all conditions, including lung cancer. So I’d love for you to talk a little bit, Dr. Rolfo about some of the challenges related to appropriate access to lung cancer care as it relates to different socio-demographic populations, and then how can we begin to address those disparities.

Dr. Christian Rolfo: 

Yeah, this is a topic that is really in my heart because I was coming with you before we start the communication, the recording of this. I was working in Europe before coming to the United States. I was shocked by the disparities that we see in some healthcare situations, so in my position before in Europe, we have a healthcare system that discovering for patients and we have, obviously, difficulties, but here I saw in some communities really underserved in terms of access to different service and healthcare is one of them. So we need to be conscious about that when we have patients that are struggling to get transportation, we have patients that are struggling to get approval for some drugs. 

So, there are a lot of areas that need to be addressed, disparity also in terms of language, we have also patients that are not understanding the doctors,  we have patients that are having difficulty when to get to the app information when we are saying, “Oh, you can see your report in your app,” so it’s not easy for some of them, we have generational gaps as well, these are disparities as well. So taking or being conscious of all these factors is making us take action and how we can take actions in our institutions, and in several institutions in the country, we have the support of an experienced team that is addressing that and teams are specific that are working for disparities. Some of them are social workers, some of them are advocate patients, so we have a big team of institutions that are helping to the patients to go for different scenarios, and even we have patients that are homeless, so how we treat patients in these conditions when we know that the patient is in a shelter, so if you have toxicity, what will we be doing. 

So all these things are taken into consideration, believe me, because it is like New York, you have a big disparity of or a big diversity, and we say of populations in one consultation morning, you can see all of them in your waiting room, so we need to try to address all this, and there are politics that are coming from us as a healthcare system, but there are also politics that they need to come from governmental politics, so try to use these…all the tools that we have at our disposal are important, and also we have a very good support of advocacy groups. 

Dr. Christian Rolfo: 

And this is something that I want to really profit their patient to say thanks because we have several, several advocacy groups that are doing a terrific job from testing to helping patients to go through this journey. So it’s really an important job, and obviously families, families are helping to these disparities and patients, so patients themself. So what I say always to the patient, raise your voice, empower yourself.

 Try to ask for your rights if you don’t understand your doctor… Ask again, if you want to have a second opinion, talk to your doctor, that is the most important thing. We are very open to help the patients, and that is our mission. So if I say to my patients, If you want to have a second opinion, please let me know, and I try to direct you to somebody who is an expert in the field and can help us to learn better your disease or your treatment, but I think it’s a situation that everyone is winning, especially the patient, but also ask for future patients understanding better every case.

Dr. Nicole Rochester: 

Well, as an independent patient advocate, myself, Dr. Rolfo, I always get super excited when physicians like yourself are talking about and emphasizing the importance of patients and families advocating for themselves, so I just want to reiterate a couple of things that you said just to make sure that our audience heard it very clearly and asking questions is one of the things that you said that is, I believe one of the most important ways that we can advocate for ourselves and for our family members in healthcare settings, and I really appreciate that you offer advice around second opinions.

A lot of people feel that they are sending their doctor if they ask for a second opinion, but a confident doctor like yourself and a good doctor is going to encourage that, particularly if the patient or family just needs that extra reassurance, so I just really appreciate that you brought that up. Before we wrap up, there are a few questions from our audience that I would love to present to you, and so one of them comes from MacKenzie and MacKenzie asked, can you speak about MRD testing and what that means for lung cancer?

Dr. Christian Rolfo: 

Yeah, and that we were discussing briefly. So minimal residual disease is the… As I say, when we have an operation, we can have the opportunity to have completely resected a tumor, but we don’t know more than with the CT scan when the patient will recover. So we are without an answer believing every follow-up visit what has happened, seeing if it has gone). So we are trying to reduce this…reduce the anxiety first of all, to try to get the tools that are able to identify patients that they can recurrence, have a recurrence so liquid biopsies, one of them, and we have now the several methods that are trials and several data coming that there are some companies that actually they are a market for some of the options, we are still having validations,  required validations, but we will certainly be there very shortly in time to identify these patients and to treat them in the proper time.

Dr. Nicole Rochester: 

Wonderful, and I think you just addressed a question that came in from Herald, which was is liquid biopsy playing a role in monitoring disease recurrence in lung cancer?

Dr. Christian Rolfo: 

Sure, we are actually tailoring treatments and checking the patients, and I have several, several experiences in patients that they’re monitoring over the time, and we have actually some of the vendors that are proposing this approach monitoring, liquid biopsy is a great tool because it’s minimally invasive, it’s just a blood draw and we can continue. Not all the patients have the possibility in terms of they are not all cheaters, that is something we need to know DNA, so it’s the majority of them, we can do it in some minimal proportion, we cannot do it when there are also possibilities to follow them.

Dr. Nicole Rochester: 

Excellent, and our last question from the audience comes from Laura, and she wants to know, “Are immunotherapy combinations in the metastatic setting, expanding to treat earlier stage lung cancer?”

Dr. Christian Rolfo: 

Yeah, absolutely, we have actually an FDA approval for us, one of the immunotherapeutic drugs in patients after the resection of the disease with some characteristics, but we are there and actually we are having more and more clinical trials using in earlier stages so we will say in the other stage from the earlier stage from that is the neoadjuvant and we call that when we are doing a treatment to reduce two months to be operated later on, so we have also some trials that are going there, but we have an approval already for the adjuvant setting that is after the surgery in some patients.

Dr. Nicole Rochester: 

That’s wonderful. You’ve given us a lot of good news. A lot of hopeful news, Dr. Rolfo, it is time for us to wrap up. I want to thank you again for being here for sharing your expertise. In closing, is there any takeaway that you want to leave with our audience today regarding lung cancer and advocating for themselves.

 Dr. Christian Rolfo: 

I will say that, first of all, thanks for the opportunity and it was a pleasure to discuss with you and I’d write to the population and say, Try to ask for your rights as a patient, so ask for your rights, be proactive in terms of your disease, you are the main actor here,  we are tools of trying to help you to arrive to the destination, but the good important thing is to create a good relation with your doctor, and to create a good relation with your doctor is part of the trust from both sides, so having an open communication… Open communication with the family as well. Sometimes we are smuggling or hiding things as a patient for our families to don’t help them, and vice versa that is not helping in this process, absolutely. And if you want, if you have that asking if you’re never deserving, so this is what we are here and all the team is here to help you.

Dr. Nicole Rochester: 

Wonderful. Well, I just want to echo what Dr. Rolfo said about asking questions about being an active member of your medical team, the doctors are there to assist you, but you are ultimately the expert for your disease for your body, so I just wanna thank you again deferral for being here for sharing such important information thank you all again for tuning into this patient empowerment network program. If you’d like to watch this webinar again, there will be a replay and you will receive an email when that recording is available, and remember, following this program, you will receive a link to a survey, please fill out that survey. Let us know what was helpful so that we can serve you better in the future to learn more about lung cancer and to access tools to help you get the best care no matter where you live. Visit powerfulpatients.org/lung cancer. I’m Nicole Rochester, thank you so much for joining us. 

MPN Research and Optimism About Curative Therapies

MPN Research and Optimism About Curative Therapies from Patient Empowerment Network on Vimeo.

Myeloproliferative neoplasm (MPN) researcher Dr. John Mascarenhas discusses why he’s excited about the future of care for patients with essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF).

Dr. John Mascarenhas is Associate Professor of Medicine at the Icahn School of Medicine at Mount Sinai (ISMMS) and the Director of the Adult Leukemia Program and Leader of Clinical Investigation within the Myeloproliferative Disorders Program at Mount Sinai. Learn more about Dr. Mascarenhas, here.

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Transcript

Katherine Banwell:

Before we close, Dr. Mascarenhas, let’s talk about research. Are there new developments that you’re excited about?

Dr. Mascarenhas:       

Absolutely. So, what I’m heavily interested in and involved in is clinical investigation and moving the field forward, and there are many people out there that are similarly involved and they’re doing really excellent work. So, I am super jazzed and enthusiastic and optimistic, and it’s what gets me work every day and inspires me is all of the effort that is happening. And, it’s a continuum. So, it’s not just one person trying to try a different drug here and there. It’s really a bringing together of many different people because these are rare diseases.

Many different people from many different institutions that have different areas of expertise, but have a common goal of translating from laboratory informed data, so, not just taking a dart and throwing it at the dartboard and hoping it sticks. But actually taking data that we learned from the lab and leveraging that information to develop therapies that are informed, that are targeted, that are personalized and going through a process of evaluating them to get them into the clinic, with the goal of, and I would say ambitiously, our goal these days is moving beyond trying to make patients feel better, which is an important goal, but it’s really can we really target the disease in a more effective way to induce remissions, to, dare I say, cure patients. So, I think the ambitious goal of the clinical investigators and laboratory investigators that are active in MPN research today is really one looking for an understanding at the basis of the biology of the  disease to develop curative therapies. And, I am optimistic that that will happen.

And, I don’t mean happen in a hundred years from now. I mean happen in our lifetime. So, that’s where we’re going. There’s a lot of very exciting drugs, oral and intravenous drugs and they target very different types of aspects of the disease, and I think patients and physicians will see that maybe those drugs are used best in combination. So, the idea of using one drug, waiting for it to fail and using another drug is really old news, and much of oncology is combination therapy. So, taking drugs that have different targets or mechanisms of action and non-overlapping toxicity to try to better target and delete what’s called the myelofibrosis stem cell that’s the basic issue here, which we don’t effectively delete other than transplant. So, our goal would be to put bone marrow transplanters out of business.

 

What To Expect When Starting MPN Inhibitor Therapy

What To Expect When Starting MPN Inhibitor Therapy from Patient Empowerment Network on Vimeo.

Changing a treatment approach for your essential thrombocythemia (ET), polycythemia vera (PV), or myelofibrosis (MF) can be intimidating. Dr. John Mascarenhas, a myeloproliferative neoplasm (MPN) specialist, shares tips and advice for beginning a new therapy.

Dr. John Mascarenhas is Associate Professor of Medicine at the Icahn School of Medicine at Mount Sinai (ISMMS) and the Director of the Adult Leukemia Program and Leader of Clinical Investigation within the Myeloproliferative Disorders Program at Mount Sinai. Learn more about Dr. Mascarenhas, here.

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Transcript

Katherine Banwell:

And we have another question from Craig that we received earlier. “I’m currently receiving regular phlebotomies for PV, but my doctor is considering switching me to inhibitor therapy. What can I expect, and are there side effects that I should be concerned about?”

Dr. Mascarenhas:       

So, for some patients, therapeutic phlebotomy is all that they need, and they do very well with it, and they don’t need to take a therapeutic like a JAK inhibitor or hydroxyurea, which is a non-specific treatment.

But some patients do. So, some patients where if their risk score is higher and their risk for thrombosis, that may be an appropriate indication. And some patients have a lot of symptoms with their PV. So, not all PV patients present and behave the same way. Some patients have a very low symptom burden. Some patients have a very significant symptom burden. Itching, for example can be a very annoying and very troublesome symptom for patients with PV.

And, if you don’t have PV or you don’t know someone with PV, you may not understand or realize the negative impact of having intractable itching, often associated with taking a shower or warm water.

And, that can really detract from quality-of-life and cause a lot of anxiety. So, that’s an example of where sometimes a JAK inhibitor like ruxolitinib can be really lifesaving in terms of restoring quality-of-life and functionality to a patient.

Usually, drugs like ruxolitinib are very well-tolerated too, which we’re fortunate about. There’s not a lot of toxicity associated with them. So, for example, nausea, vomiting, diarrhea, hair falling out with chemotherapeutics, you really don’t see with ruxolitinib or Jakafi. Easy bruising, headaches and some dizziness up front sometimes may be seen. They’re usually low-grade and they’re usually fleeting. And usually, the benefit, the feel-good aspect of it outweighs toxicity that can be seen with the drugs. They are immunomodulatory drugs. So, ruxolitinib or Jakafi may increase, to some small extent, but likely, real extent, infectious complications like shingles, urinary tract infections, upper respiratory infections. So, sometimes there is this increased risk. It’s often outweighed by the benefit of the drug.

But there are risks that are associated, and of course the results are not guaranteed. So, I always warn patients, be careful when you look at the package inserts or talk to the physicians. Risks are risks. They’re not guaranteed. So, most patients don’t have these toxicities, but one is at risk for toxicity whenever they take any medication.

An Overview of ET, PV and MF Treatment Options

An Overview of ET, PV and MF Treatment Options from Patient Empowerment Network on Vimeo.

Treatment for essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF) can vary greatly. Dr. John Mascarenhas breaks down the treatment types and the goals of treatment for each type of myeloproliferative neoplasm (MPN).

Dr. John Mascarenhas is Associate Professor of Medicine at the Icahn School of Medicine at Mount Sinai (ISMMS) and the Director of the Adult Leukemia Program and Leader of Clinical Investigation within the Myeloproliferative Disorders Program at Mount Sinai. Learn more about Dr. Mascarenhas, here.

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Transcript

Katherine Banwell:

Depending on the patient, it seems like ET or PV may be easily managed. So, how are they treated? Let’s start with essential thrombocythemia or ET.

Dr. Mascarenhas:       

So, ET is a disease in which first and foremost, we’re trying to reduce the risk of thrombosis, clotting, and/or hemorrhage bleeding. So, typically, ET patients are risk stratified by low risk or high risk.

It’s almost simply based on their age, whether they’ve had a clot in the past, and some systems now even incorporate other factors like mutation status. And, you tailor the treatment based on their risk score. So, low risk ET patients don’t necessarily need to be treated. They can be followed expectantly and watched. The height of the platelet count does not predict thrombotic risk. So, we don’t treat the platelet count per se. A high-risk patient is at high risk for clotting. So, these patients almost invariably are getting aspirin at a baseline, and they are often on cytoreductive therapy. And sometimes, that is chemotherapy like hydroxyurea. Sometimes it’s a non-chemotherapeutic option and like anagrelide, and sometimes it’s a biologic therapy like interferon alfa either 2a, Pegasys, or 2b ropeginterferon. And, these are therapies that have rationale, that have clinical data, that have demonstrated reduction in risk of clotting, which again is the reason why we treat high-risk ET patients.

Katherine Banwell:                  

And, what about PV, polycythemia vera?

Dr. Mascarenhas:     

So, in polycythemia vera, it’s similar to ET. We risk stratify patients low and high risk based on age and clotting histories. And whether you’re low or high risk, we give PV patients aspirin or at least once daily, and we look to keep their hematocrit below a threshold of 45 percent. And sometimes in women, we even go lower, to 42  percent. But the idea is that controlling the hematocrit, which is one of the red blood cells indices, you reduce the risk of having clots, and that’s been shown actually many years ago and reinforced in a very well-known study called the CYTO-PV study in Italy documented that if you keep the hematocrit less than 45 percent, so, stringent control versus allowing for less stringent control between 45 to 50, that you reduce by fourfold the number of cardiovascular events that can occur.

So, we know that controlling the hematocrit is important, and that can be done, again, with hydroxyurea, interferon, and ruxolitinib.

The JAK2 inhibitor has also proved specifically for patients who had an intolerance or refractory hydroxyurea, but also importantly as a drug that can address, probably better than most drugs in this field, the symptom burden that could be problematic for some of those patients. But, it’s really about controlling the hematocrit.

Katherine Banwell:                  

Yeah. Since myelofibrosis is a progressive condition, I imagine that makes it more difficult to manage. So, what else is available for patients with myelofibrosis?

Dr. Mascarenhas:       

The first line of treatment is typically a JAK inhibitor, although I would say that there are a subset of patients – well, there are patients we sometimes meet that have very low risk disease. They don’t have those clinical variables we discussed before that could uptick their risk score, and some of those patients can be watched.

And interestingly, there are a subset of patients that can have an indolent or slow form of the disease where they don’t have aggressive changes in their disease, their blood counts, their symptoms, their spleen, and don’t need immediate treatment. Most patients would benefit from a JAK inhibitor, although there are a subset of patients where their issue is less simple in spleen burden and it’s more anemia.

So, we take those patients where anemia’s the focus, we look at their erythropoietin level, which is their endogenous hormone level that regulates red blood cell production. If it’s low, we give them a lab-based form of erythropoietin, something called Procrit or Aranesp. If it’s high, we will move on. We can use a drug called danazol, which is a synthetic male androgen which can improve hemoglobin levels in 20 to 40 percent of patients. Or, we can use a drug called lenalidomide, which is an immunomodulatory drug. And, more recently, there’s a drug in testing called to luspatercept, which is an active activin receptor ligand trap. So, there is a growing armamentarium of drugs that can be used to try to alleviate the anemia which is present and can be a significant issue in about a quarter of patients with myelofibrosis upfront at time of diagnosis or about 75  percent through the course of their disease. So, that’s an unmet need that still requires attention and may alter the treatment plan for a given patient.

Katherine Banwell:                  

What about stem cell transplants?

Dr. Mascarenhas:       

So, we relegate stem cell plant transplants for those patients as mentioned before that are higher risk because we think that the potential benefit-to-risk ratio is in favor of transplant.

Transplant is really a modality that is the only modality that offers the potential for cure, but it’s also a modality that poses a significant risk of morbidity and mortality associated with it. So, it has to really be taken very seriously. It can’t be the kind of treatment you would think of as a last resort at the last minute. Once you see a transplanter, if they’re interested in that therapy and see it early on in the disease course, in my opinion, to start that dialog and then figure out when is the optimal time to employ a bone marrow transplant, which is not a surgical procedure. It’s often thought to be surgical. It’s not a transplant of an organ. It’s a transplant of hematopoietic cells. So, it’s really an infusion of stem cells that then end up in the person’s bone marrow, and they create a whole new hematopoietic system and immune system. And with that, you can have an immune system that then goes after the myelofibrosis stem cells.

That’s called graft-versus-leukemia effect. But with that included graft-versus-host disease, which is when the new graft, the new immune system doesn’t always recognize well the person’s own tissues, whether it’s the liver, or the lung, or the skin, and you can have immunologic reactions to that.

So, that’s a complex discussion. But, transplant, typically for patients less than 70 years of age who have high-risk myelofibrosis or even up to 75 if they have a good performance status and as we said don’t have a lot of comorbid issues with a goal of cure. So, if you have someone where their goal is to try to maximize their time out of the hospital and they’re not focused on longevity, their focused on quality of life, that may not be an appropriate patient for transplantation.

So, I think a very upfront, honest and a transparent discussion with the patient about what to expect with transplant, what are the pros and cons, what are the risks involved, and importantly does it match up with their expectations or their desires.

What Are the Benefits of MPN Inhibitor Treatment?

What Are the Benefits of MPN Inhibitor Treatment? from Patient Empowerment Network on Vimeo.

MPN expert Dr. John Mascarenhas shares an overview of how inhibitor therapy works to treat myelofibrosis (MF) and the benefits of this type of treatment.

Dr. John Mascarenhas is Associate Professor of Medicine at the Icahn School of Medicine at Mount Sinai (ISMMS) and the Director of the Adult Leukemia Program and Leader of Clinical Investigation within the Myeloproliferative Disorders Program at Mount Sinai. Learn more about Dr. Mascarenhas, here.

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Transcript

Katherine Banwell:

Dr. Mascarenhas, what is inhibitor therapy and how does that work?

Dr. Mascarenhas:       

So, inhibitor therapy in general are usually oral drugs for the most part, small molecule inhibitors that are geared and usually specific but not totally specific because then they can have off-target effects, but geared to inhibiting usually an enzyme that is overactive or is contributing to the pathophysiology of the disease.

I think in MF, probably one of the best examples is a JAK2 inhibitor. So, there are a number of JAK2 inhibitors that have been in clinical testing. There are two that are approved, ruxolitinib and fedratinib which are excellent drugs in inhibiting JAK2 protein itself in the cells that could be either upregulated or hyperactive in the signaling pathway, and it quiets down a signaling pathway in the hematopoietic cells that leads to a lot of the manifestations of the disease, namely symptoms and spleen.

So, one of the clear benefits of JAK inhibitors that was established many years ago and reinforced by multiple drugs that are either approved or in late-stage testing is these drugs are excellent in improving the symptom burden in the patients and reducing their spleen. Unfortunately, as a class, we’ve not seen these drugs induce remissions or cure patients. So, there’s still interest in developing, obviously, non-JAK inhibitor therapies. But inhibitors in general are inhibiting proteins that are either inappropriately activated or part of a cascade of signaling molecules that are contributing to the disease.

And they are not chemotherapeutic, which might be an important point to make. In past days, we’ve relied heavily in hematologic malignancies in using chemotherapies which are nonspecific and just kill dividing cells whereas inhibitors typically are targeted, and in some sense, it’s personalized to the disease with toxicity profiles that are usually quite distinct from the traditional chemotherapies that we use.