Tag Archive for: Mount Sinai

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

Related Resources:

Essential Small Cell Lung Cancer Testing

Essential Small Cell Lung Cancer Testing 

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

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

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

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

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Lung Cancer Treatment Landscape Overview

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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.  

 

How Do MPNs Progress From One Disease to the Next?

How Do MPNs Progress From One Disease to the Next? from Patient Empowerment Network on Vimeo.

Understanding how essential thrombocythemia (ET), polycythemia vera (PV), or myelofibrosis (MF) are connected may be confusing to patients. Dr. John Mascarenhas, an expert in myeloproliferative neoplasms (MPNs), provides an overview of how the conditions are defined and how they may progress from one condition to the next.

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: 

As we move through today’s program, which is going to cover the three classic MPNs, polycythemia vera, essential thrombocythemia and myelofibrosis. So, for someone who has one of these conditions, can you help us understand how one may progress to the next?

Dr. Mascarenhas:

So, these are a very heterogeneous or variable group of diseases that are under an umbrella called the myeloproliferative neoplasm. So, MPNs can really present and behave and have very different clinical courses. So, I think it’s very important for patients to realize that these are rare diseases, that that has a complexity to it because they don’t always have the ability or the privilege to know other patients or people in their lives that may have these diseases. So, it could be very frightening from a level of feeling isolated or alone with a diagnosis like this and not having familiarity, but also, that these are vague diagnoses in the sense that when you have breast cancer, one can kind of conceptualize that there is a mass in the breast, for example, and that that can be staged. It can go to the lymph nodes in the armpit, it could spread below. And people can kind of understand that concept. I think it’s a little bit more challenging when you talk about MPNs because it’s a little bit more abstract.

These diseases are within the bone marrows at diagnosis. So, they’re not staged in a physical way, and they are complex because they can lead to high blood counts, low blood counts, different types of symptoms, and the approaches really have to be personalized. They are all three interrelated because there are commonalities. So, there are certain clinical commonalities and also biologic commonalities. So, for example, the JAK2 mutation, the JAK2V617F mutation is seen in all three diseases. So, it’s not specific to one or the other.

It’s more common in polycythemia vera, but in about 50 percent of patients with ET, and 50 percent of patients with MF, you can see this mutation. So, the mutation alone doesn’t really tell us what the disease is. It just tells us you have one of these diseases. And, there are other mutations. So, a bone marrow biopsy then becomes integral in helping subtype the patient and then create that treatment plan and that outlook that’s specific for that disease.

And as you mentioned, to make it even more complicated, these diseases can overlap not just biologically, but in a continuum. So, patients with ET or polycythemia vera can progress in some cases to myelofibrosis. And, all three diseases in a minority of patients can progress or evolve into acute myeloid leukemia, which is a more aggressive form of bone marrow cancer.

Patient Considerations That Impact MPN Treatment Decisions

Patient Considerations That Impact MPN Treatment Decisions from Patient Empowerment Network on Vimeo.

How can personal choices play a role in your MPN care? Dr. John Mascarenhas reviews factors that should be considered, including lifestyle and overall health, when choosing therapy for essential thrombocythemia (ET), polycythemia vera (PV), or 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:

Outside of testing, what other factors should be considered when choosing treatment?

Dr. Mascarenhas:       

I think patient expectation. So, sometimes physicians and family will impose what they want for a patient, and that may not be what the patient really wants. So, I have learned over the years that it’s crucial to make sure that you understand the patient and what the patient’s expectations, desires, and that’s influenced by the life they’ve lead or the remaining life that they want to live and their own personal religious and spiritual beliefs.

So, I think knowing your patient and understanding what their expectations are, it’s fundamental, and sometimes, it’s overlooked. So, understanding that, I think, is very crucial. And then, dividing what are the objectives of the treatment in a given patient? Is it really to improve anemia in some patient versus perhaps a different patient, it may be to improve their quality of life and reduce their symptom burden. And then in other patients, it may be purely trying to cure the disease with therapies that may be aggressive, which may not be appropriate for an older patient where toxicity could outweigh any potential benefit of survival or longevity. So, you really have to have a discussion with the patient or caregivers, and then define what are the goals in that individual to personalize that approach for that patient.

Katherine Banwell:                  

Right. Right. And, there’s the patient’s overall health, comorbidities, other things like that?

Dr. Mascarenhas:       

Yeah, because we are not treating a disease in isolation usually. So, patients come with baggage posed of past diseases, current diseases.

And sometimes patients are not “fit” for certain types of therapies because they may be sick or they may have organ dysfunction that would make certain types of treatment approaches ill-advised because the toxicity could be higher. So, absolutely, you need to know their comorbid index, how much comorbidities they have and also their performance status, how active and how well they are in general.

Katherine Banwell:                  

Are there specific biomarkers that may affect prognosis or treatment?

Dr. Mascarenhas:       

So, yes and no. I mean, I think that’s an area of intense interest and research. So, we have identified certain biomarkers that have, as I mentioned, prognostic significance, and that may influence treatment decisions. So, patients who have, for example, as we discussed next-generation sequencing and we see their mutations that are present, if they have an accumulation of high molecular risk mutations, that may give us a sense that perhaps that patient may not enjoy the full benefit and duration of benefit of, for example, a JAK inhibitor as another patient that has a less complex disease.

And, that doesn’t necessarily mean that the therapy is not appropriate for the patient. But it may help us plan and be prepared to move on to the next therapy sooner or to be more vigilant for changes that would tell us it’s time to move on. So, I think they help us maybe get a general sense of things and put things into perspective. They don’t always necessarily inform us on a change in therapy immediately or the next or the most immediate therapy. But I do think that that will change because I would predict in the next five to 10 years, I think that the number of available drugs for myelofibrosis, for example, will likely double from what it is now. I think we will have an armamentarium to choose from, and what we will learn from trials that are ongoing is there may be certain profiles, mutations, chromosomal profiles, other clinical variable profiles that we will learn from these trials that will help us to find upfront, “Well, this profile really should go with his medication. That profile should go with that medication.”

An early of example that would be we’re learning that not all patients with the JAK2 mutation are created equal, that you can have different burdens of JAK2 mutation.

And, patients with low burden JAK2 mutation, for example, may fare better with up a specific JAK to inhibitor like pacritinib than patients who get treated with other JAK inhibitors like ruxolitinib.

So, there are differences even within patient defined by mutation that may help us predict which of the JAK inhibitors, as an example, may be more appropriate as a first-line therapy. So, I think that will evolve more so over the next five to 10 years.

What Questions Should Patients Ask About MPN Test Results?

What Questions Should Patients Ask About MPN Test Results? from Patient Empowerment Network on Vimeo.

What should you know about your MPN test results? Dr. Mascarenhas discusses how test results are used, including the importance of genetic mutations and risk stratification when analyzing results.

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: 

Some patients may not know if they’ve received these important tests. So, what key questions should they ask their physician about testing?

Dr. Mascarenhas:       

Well, I think it’s important that the patients feel empowered to understand sort of where the field is and what key questions you would ask a physician, hematologist who’s taking care of you. So, I think all patients should be aware of their diagnosis, the name of the diagnosis, the subtype, but also do they have any of the key driving mutations, the JAK2 mutation, the calreticulin mutation, the MPL mutation, and that’s usually done off of a bone marrow biopsy sample, but it can be done off peripheral blood. And, they may not always know that it’s done. So, I think having a discussion with the position to understand there are criteria that exist called the World Health Organization criteria that are updated frequently and should set a standard throughout the world of how you diagnose and establish these diagnoses.

So, I think it’s important for physicians to be able to convey to the patients with confidence, “We follow these criteria and you have these criteria and we’ve done this testing that shows that you have these mutations.” And not just regurgitate what they found, but help them understand and navigate with that means, which again, I will point out that sometimes we don’t know. But, I think it’s important for physicians to convey sometimes that some of the findings that they may see, for example, patients look on portals these days and they can look at their labs and stuff like that. And, we don’t always have a terrific answer or an informed answer for everything that we get back. And, we will potentially in 10 years from now, but sometimes at the moment, we don’t. But, I think a discussion about the meaning of the labs that are obtained is probably good for the patient to understand what’s being done.

Katherine Ba:nwell:

Absolutely. It sounds like each person’s situation is unique and should be considered before making any treatment choices. Can you talk about how the results of these tests may affect prognosis and treatment?

Dr. Mascarenhas:     

So, we do have risk stratification systems that we use for essential thrombocythemia, polycythemia vera, and myelofibrosis. I’ll talk about myelofibrosis because that’s probably a little bit more of a complex and sophisticated model. It’s also changing, and we update it frequently. And, these models are imperfect, so I always warn patients to not put all of their money in one basket when we talk about risk stratification. They broadly help us understand where a patient is in their disease course. So, for example, in myelofibrosis, historically, the DIPSS, the Dynamic International Prognostic Scoring System is used, which considered five clinical variables that have been shown to be independently prognostic. So, at age over 65, the presence of blasts or circulating immature cells in the peripheral blood, anemia, hemoglobin less than 10, symptoms, fevers, night sweats, weight loss or a high white count over 25,000, you those points up.

And patients can do this online. There are calculators that you can calculate your DIPSS score. And, you’ll see that there are four different risk groups that range from low risk to high risk, and they are associated with median survivals. We now know that mutations influence those, have influence on prognosis. So, there are a group of high molecular risk mutations like ASXL1, SRSF2, IDH1/2. So, there are mutations that also have prognostic significance, and we incorporate them into the decision-making.

And, essentially, and this is where I think patients have to be very careful, physicians have to be very careful with conveying this. With these risk models whether they are clinical variable risk models or these integrated molecular risk models, each category is associated with a median survival, that’s based on retrospective studies. But that doesn’t tell the patient specifically what they should expect in terms of survival. And, I always fear that patients, when they look at these things, or even physicians when they convey them that they may inadvertently misrepresent or convey what those really mean.

And, I think the purpose of those risk stratifications is really to help guide a risk adapted treatment approach that’s reasonable and is weighted for benefit to risk of the disease. So, for example, if you have advanced disease with a high-risk score of intermediate to or higher, bone marrow transplant in certain patients may be a warranted therapy to consider. So, they really help inform treatment.

 

Which Tests Do You Need Following an MPN Diagnosis?

Which Tests Do You Need Following an MPN Diagnosis? from Patient Empowerment Network on Vimeo.

After a diagnosis of essential thrombocythemia (ET), polycythemia vera (PV), or myelofibrosis (MF), what testing should take place? Dr. John Mascarenhas shares an overview of essential and in-depth testing for patients with myeloproliferative neoplasms (MPNs).

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: 

What tests are necessary to help understand a patient’s specific disease at diagnosis?

Dr. Mascarenhas:

Usually, the blood counts are the first opening door test that allows some understanding of, again, either an abnormal production of red blood cells, platelets or under production of these cells. And, that’s really where often the evaluation begins. And then, there are further blood tests that often are done.

And I would say almost indefinitely or almost definitely one should have a bone marrow biopsy that helps categorize the type of myeloproliferative neoplasm because there can be overlap in how the blood counts can look from one disease to the next and overlap in the mutations like the JAK2 mutation. So, sometimes, the blood counts and the molecular testing are not enough, and a bone marrow biopsy looking under the microscope at the different types of cells, the proportion of cells, whether there’s fibrosis where there’s others other types of cells that shouldn’t be there and they’re looking at the chromosomes and the flow cytometry, these are associated tests. As well as almost probably anywhere anyone goes at this point, they’re going to get next-generation sequencing, which is looking at multiple genes and mutations, and that gives a more broader, deeper sense of the disease.

So, those really become the integral parts. In some cases, patients will end up getting imaging of their abdomen to see if they have an enlarged spleen or enlarged liver.

Although that’s not always necessary, that is often part of the workup. So, it’s bloodwork, it’s bone marrow biopsy, sometimes imaging is usually the cornerstone.

Katherine Banwell: 

And, what is molecular or biomarker testing?

Dr. Mascarenhas:    

So, molecular testing today really means – at one point, it really meant looking at PCR for specific gene mutations.

So, for example, we would look at the JAK2 and we would say, “In a given person, is this gene mutated?” We all have JAK2 gene, but in patients with these diseases, they’re more commonly mutated which means altered in the blood cells. And, it’s very important for a patient to understand not in every cell in their bodies, but in their blood cell compartment. And, that helps us understand and start characterizing their disease, and sometimes that mutation can be measured. It can be at a low level. It could be a high level. And, that’s all put together in trying to understand the molecular basis of these diseases.

Today, next-generation sequencing has really taken over and that’s looking at more than just one gene.

Its sequencing could be 40 genes, it could be 200 genes, to get a sense of the complexity of the disease and looking for certain mutations which are considered biomarkers that can portend prognosis or I think increasingly, we’ll see may inform treatment decisions and may even be targets themselves of therapies.

Katherine Banwell:              

Right. Should all patients diagnosed with ET, PV, or MF undergo biomarker testing? Is that necessary?

Dr. Mascarenhas:       

I would say it’s part of the modern evaluation and management of patients today. I don’t think that that was true 10 years ago. But, I think the field has matured. I will say I’m the first person to acknowledge to patients that we get a lot of information back, and the truth is we don’t often know what to do with all of that information. So, sometimes we get information back that can cause anxiety because you can see mutations in genes. But they don’t always inform us on how to educate the patient about their disease or tell us what to do with the treatment.

So, there is still a lag as there normally would be between the testing of the results that we get, and then the actual knowledge of what to do with that. And, that’s still a process that’s in evolution.

What Is Personalized Medicine for ET, PV & MF?

What Is Personalized Medicine for ET, PV & MF? from Patient Empowerment Network on Vimeo.

MPN expert Dr. John Mascarenhas defines personalized medicine and how the approach is used in 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 delve into our discussion, let’s start with a term we’ve been hearing a lot about recently. How would you define “personalized medicine?”

Dr. Mascarenhas:    

So, it’s a good question because I think it’s poorly defined in many ways because it can mean different things I think to different people. And, it’s a definition that’s in evolution. So, I think at its core, personalized medicine tries to embody the concept of creating an evaluation and management plan that is specific of tailored to that patient on multiple levels.

On a personal level, on an objective level of what the patient’s objectives are with their therapy or their disease, and then on a biologic level in terms of the type of disease, and now increasingly, on a molecular level. So, in some cases, it may be personalized therapeutics that are specific or targeted to certain mutations that the patient may have. And, that’s kind of where things are evolving from a treatment perspective. And to me, personalized medicine should be the goal of any interaction with a patient that you have to personalize the approach. Because, every patient that we meet is quite different and distinct from the next patient, and their own sensitivities, understandings and desires can be quite different. So, you want to personalize that approach to that patient at the most basic level.

Which MPN Treatment Is Right for You? What You Need to Know Resource Guide

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