Tag Archive for: BiTE

Updates in Myelofibrosis Research From an Expert

 
Dr. John Mascarenhas shares updates on myelofibrosis research. Dr. Mascarenhas highlights the shift towards combination therapies, particularly the use of JAK inhibitors alongside novel agents, with the goal of improving disease response and patient outcomes.
 
Dr. John Mascarenhas is Professor of Medicine at the Icahn School of Medicine at Mount Sinai (ISMMS) and the Director of the Adult Leukemia Program and Director of the Center of Excellence for Blood Cancers and Myeloid Disorders at Mount Sinai. Learn more about Dr. Mascarenhas.

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Transcript:

Dr. John Mascarenhas:

My name is John Mascarenhas, I am a professor of medicine at the Icahn School of Medicine here in New York City. I direct the Center of Excellence for Blood Cancers and Myeloid Disorders, and I lead the adult leukemia program. But my real passion and interest is in myeloproliferative neoplasms and translational research, trying to understand the biology of the diseases and helping translate that into effective therapies in the clinic. 

Katherine Banwell:

Dr. Mascarenhas, from your perspective, what are the highlights so far this year in myelofibrosis research? 

Dr. John Mascarenhas:

So, I think myelofibrosis research – I’ve been in this field for about 20 years, and I’ve watched it go from a field where we had very little insight into the biology of the disease, which meant very little targeted or informed therapies to the era of JAK inhibitors.  

The first being 2011 with ruxolitinib (Jakafi), then 2019 with fedratinib, 2022 with pacritinib, and then 2023 with momelotinib (Inrebic), has really afforded us a significant advantage in trying to tailor the treatments for different patient niches to improve spleen and symptom benefit.  

And I do think that translates to a survival benefit in our patients with myelofibrosis. So, outside of bone marrow transplant, really these treatments are not curing patients, but they are addressing certain aspects of the disease. 

What I’m most excited about is the new era; the next generation of approaches that we’re seeing, and we have been seeing, and will continue to see emerge, and these include combination therapy approaches up front. So, taking those JAK inhibitors, the benefit they have, and trying to improve upon that with the addition of informed therapies, rational drugs that have pre-clinical evidence. 

Meaning, in the lab with cells from patients with animals that are engineered to have myelofibrosis, so that when we take them into the clinic, we are more confident, more informed in our decision-making, that we’re not exposing patients to drugs that really don’t have rationale.

Katherine Banwell:

What do these research advances mean for myelofibrosis patients? 

Dr. John Mascarenhas:

Well, I think what we’re seeing is a shift towards more combination therapy. So, what I think it means for a patient is deeper responses from not just spleen and symptom, but what we’re looking at very intently are biomarkers of disease modulation and disease response, hopefully, disease course changes.  

So, things like reductions in their driver mutation. These are gene mutations like JAK2, CALR, MPL, reductions in inflammatory markers, reduction in bone marrow fibrosis in the bone marrow.  

All of these things suggest that we’re really starting to modulate the disease in a more significant way. What we’re trying to show is that that actually matters to a patient, that these findings actually translate to better progression-free survival, better overall survival. So, I’m really enthusiastic and excited by what is happening now, because I do think it pays off. 

It’s incremental benefits, but things that are now more targeted, like mutant CALR antibody approaches, or BiTE approaches.  

To those patients who have this abnormal CALR protein expressed on the surface of the cell transformative with at least the potential to be JAK2 selective inhibitors, really going after that mutant JAK2 in a very selective way, or a Type II JAK2 inhibitor. Really, the potential to have very molecularly defined targeted therapies that will, hopefully, get us much deeper responses; that patients will see even greater benefits, better improvements in symptom burden, spleen, but ultimately survival.  

Exciting Advances in Waldenström Macroglobulinemia (WM) Treatment

Exciting Advances in Waldenström Macroglobulinemia (WM) Treatment from Patient Empowerment Network on Vimeo.

What new therapies are on the horizon for patients with Waldenström macroglobulinemia (WM)? Dr. Shayna Sarosiek from Dana-Farber Cancer Institute reviews promising developments in WM treatment, including immunotherapy and BTK inhibitors.

 Dr. Shayna Sarosiek is a hematologist and oncologist at the Dana-Farber Cancer Institute where she cares for Waldenström macroglobulinemia (WM) patients at the Bing Center for Waldenstrom’s. Dr. Sarsosiek is also Assistant Professor of Medicine at Harvard Medical School. Learn more about Dr. Sarosiek, here.

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Transcript:

Katherine:

What are you excited about when it comes to Waldenstrom’s research? 

Dr. Sarosiek:

So, there a couple of things that I find really exciting right now. One thing in particular is currently for treatment for Waldenstrom’s, we often use BTK inhibitors. So, the group of medications that includes zanubrutinib (Brukinsa), ibrutinib (Imbruvica), acalabrutinib (Calquence). And that class of medications has really revolutionized treatment for Waldenstrom’s. But sometimes patients become resistant to those medications. And there’s a new group in that same class of what’s called BTK inhibitors.  

And those are non-covalent BTK inhibitors. And those drugs actually work often for patients who progress on initial therapy with ibrutinib or zanubrutinib. So that really, I think is game changing. There are some early Non-Covalent BTK inhibitors that are in trials. And I really think it’s going to lead to use of those medications very commonly in the future for Waldenstrom’s. So, that I think is exciting to have a next oral therapy to go to after progression on the current therapies. I’m also excited about new combinations that are being tried in Waldenstrom’s.  

So, using combinations of different oral therapies together that would offer deep responses and also offer a time-limited therapy. Because right now many of our treatments are given indefinitely. And so, offering a limited therapy. So, I think that, and there are many other things I could go on for a long time about this. But there are many things that I think are really exciting and we’re going to be changing the field in the coming years. 

Katherine:

Dr. Sarosiek, what is immunotherapy? Could you define that and also, how does it work to treat Waldenstrom’s? 

Dr. Sarosiek:

So, immunotherapy includes many different types of medications. But these are all medications that either use the patient’s immune system or use something from the immune system, like an antibody to help fight off a cancer. And this plays a huge role currently and I think it will continue to in the future. So, probably the most common immunotherapy that patients are familiar with, with Waldenstrom’s now is rituximab (Rituxan). So, that’s a monoclonal antibody.  

And that’s used in many combinations in Waldenstrom’s and is a very important therapy currently. And that antibody is essentially just goes into where the cancer cells are located and attacks that type of cell.  

But the other immunotherapies that are up and coming – which I think are important for patients to know about – one is CAR-T cell therapy. So, a lot of patients ask me about that. and that’s essentially, a T cell is part of the immune system that every patient has. And what CAR T-cell therapies do is patients can collect from their bloodstream – the physicians can collect T cells and then they modify those T-cells in a way so that they’ll recognized the cancer and attack the cancer.  

And so then, those T cells are given back to the patient and then that T  cell can go and work with the patient’s immune system to destroy the cancer. And that’s been very successful in a lot of other cancers and is being used in Waldenstrom’s now. And I think we’re going to be learning a lot about that and it’s going to be an important part of the future with immunotherapy involved in Waldenstrom’s. Another therapy similar is something called BiTE therapies. So, Bispecific T-cell engagers.  

So, that’s essentially two antibodies together. One antibody kind of pulls in the cancer cell and one antibody pulls in the immune system. So, when that treatment is given to patients it kind of brings the immune system close to the cancer cells. So, your own immune system can help fight off the cancer. So, those are just kind of two of the newer immunotherapies that are up and coming that I think will play an important role in the future in this disease. 

Katherine:

Who is this treatment right for? 

Dr. Sarosiek:

Immunotherapies in general currently we’re using them – currently immunotherapies are being used in patients who have had a relapsed disease. So, they have already had current available therapies, like BTK inhibitors or rituximab. And there are clinical trials that can use CAR-T cell therapy. And there are up and coming trials with BITE therapy. So, right now it’s being used in their relapse setting. But as we learn more about it, it’s possible those we moved earlier on to patients who are earlier in their disease course. 

Katherine:

What kind of side effects should patients be aware of? 

Dr. Sarosiek:

So, the side effects can vary depending on what the therapy is. So, patients who are getting rituximab, the currently available immunotherapy, patients can have infusion reactions. So, as your body is kind of getting used to that monoclonal antibody coming in, you can have a reaction. And in that case, we have to stop the infusion, wait for the side effects to settle down, and then restart.  

Katherine:

What type of side effects would they be? 

Dr. Sarosiek:

So, side effects from rituximab infusions can really vary. In some patients it can be similar to an allergic reaction. So, let’s say itchy throat or a rash or hives. Sometimes it can be pain in the chest or the back or trouble breathing. So, they can really vary. But most of the time, those can – when the infusion is stopped, we can give patients medications like Benadryl or Tylenol to help with symptoms. And then we can restart the Rituximab at a lower rate. And that lower rate allows the patient’s body to kind of get used to the medication and continue on the treatment. So that’s generally the things we watch for with Rituximab.