Jonathon Cohen, MD, MS, Associate Professor in the Department of Hematology and Medical Oncology at the Emory University School of Medicine, discusses how he came to focus on lymphoma, as well as current research, pressing questions, and potentially paradigm-shifting data in the field of mantle cell lymphoma (MCL).
Where did you grow up and how did you first become interested in medicine? I lived in Florida for most of my childhood. Then we moved around a little bit. I spent some time in southwest Virginia and went to high school in Jacksonville, Florida.
I was always interested in medicine from a young age. I think I was just interested in the science. As I got to college, I started some of the pre-med classes, and it just went from there. I had some experiences in the clinic. I wouldn’t say I had an “aha” moment. It just always felt like the right thing. As I learned more about the field, I became that much more interested.
What led to your specialization in hematologic oncology, and lymphoma in particular? I was always somewhat interested in oncology. I had family members who dealt with cancer.
My first real experience in the field was with my father-in-law, who’s now a retired oncologist. When my wife and I were dating in college, I would go to visit her family over the holidays, and he would sometimes take me to work with him so I could see what his day-to-day life was like.
One thing I really liked about oncology is that you get to manage all different aspects of a patient’s health care. In addition to managing the cancer, there’s a good amount of psychology involved. We also evaluate a lot of infections, pulmonary issues, cardiac issues, etc. You get to use the breadth of your internal medicine knowledge.
My journey to the field of lymphoma was a matter of being in the right place at the right time, with the right mentor. I did my fellowship at Ohio State University. As first-year fellows, we were assigned to a clinic, and I was assigned to Dr. Kristie Blum’s clinic. She was our fellowship director but also led the lymphoma program. I immediately found that was where I wanted to be. I enjoyed the science of it. I enjoyed taking care of patients—a wide range from young to old. Dr. Blum got me involved with clinical research and lymphoma.
Can you tell us about some of the research and clinical trials you’re currently working on? I spend most of my time on two different aspects of research. One is developing and carrying out clinical trials. The other is what we call outcomes research, or real-world evidence, where we’re keeping track of how patients are being treated, what their outcomes are, and what some of the factors are that may impact those outcomes.
From the clinical trials standpoint, my primary focus is on a fairly rare subtype of lymphoma, MCL. I have developed studies on frontline treatments, as well as studies of patients in whom the diseases recur.
In the outcomes work, I’m a part of two large consortia in the United States that are evaluating newly diagnosed—as well as relapsed—patients with lymphoma. We are trying to learn more about the disease through those endeavors as well.
In your outcomes research, is there anything you found that is surprising or unexpected? Or anything that confirmed something that you saw on an experiential level in the clinic? There are a couple projects we’ve been involved with that have done both of those things.
The first is that most of us recognize that being physically active and exercising is important just for our general health. We’ve done some projects now in collaboration with other centers that have suggested that being physically active likely leads to patients with lymphoma living longer. That has become a big part of what I discuss with patients, the importance of being active and maintaining that activity level.
Another finding has been surprising to me. The lymphoma community is relatively small, so my sense was that there are some agreed-upon treatment parameters. But what we found with some of these projects is just how varied the treatment is from center to center and from region to region. It doesn’t necessarily mean that the treatment is bad or wrong, it’s just different. This is becoming more apparent as we put together these larger-scale projects.
I’ll give you an example. Historically, it has been “assumed” that hematopoietic stem cell transplant is an important part of treatment for MCL. It has become clear from several projects that a minority of patients actually receive a transplant. There’s a number of reasons why that could be. It could be because some people don’t feel like transplant is that important. Maybe those patients live far away from a transplant center.
You see at national meetings that people will start off a talk on MCL saying, “The standard of care is to get chemotherapy followed by a transplant.” But then when you actually look at what’s happening, that’s not always the case.
What are your thoughts on the role of transplant in MCL? My thoughts on that are evolving. Until recently, I felt it was probably important, or appropriate, for patients who are young and fit.
There’s a large study that was presented at the 2022 American Society of Hematology (ASH) Annual Meeting and Exhibition that brings that into question, especially for those who receive a newer therapy called ibrutinib. It may be that those patients can receive ibrutinib and don’t necessarily need a transplant. My guess would be that in the next six to 12 months, if not sooner, there’s going to be a shift in how that is approached in patients for whom the Bruton’s tyrosine kinase (BTK) inhibitor is indicative and appropriate.
I think there’s going to be a transition period where it’s going to be complicated. Then, hopefully, we’ll settle on some sort of agreed-upon approach.
What do you see as the major challenges and unmet needs in the field of MCL? There are a few issues. The first is, many patients with relapsed disease who receive a BTK inhibitor do well; however, when they ultimately progress, we know that for those patients, chimeric antigen receptor (CAR) T-cell therapy is active. But CAR-T isn’t always available or, for whatever reason, may not always be feasible.
For those patients, we don’t really have great options. Those are patients who need clinical trials. But as a standard approach, we don’t have a lot of great approaches.
In those patients who progress after CAR-T, we really struggle. In the handful of patients I’ve encountered who have had that experience, it has been very challenging to get their disease back under control. That is an area where we are falling short and need to improve therapies.
Although there has been a lot of interest and research done, we still don’t do that well at risk stratifying patients up front and tailoring therapy appropriately.
A young patient who is eligible for it will still receive pretty intensive chemotherapy, and then you can talk about transplant. But there may be some patients who have a very indolent or slow-growing process who may not need therapy at all or might be able to get by with less-intensive therapy.
There is a lot we still haven’t hashed out. Even though those patients tend to do well, we’re probably overtreating at least some of them.
What do you think are some of the most pressing questions in MCL that still need to be addressed? One of the biggest questions is going to be, “What, if anything, is the role for transplant?” Are there patients for whom transplant is still preferred? Are there patients where it hinders their overall disease course? Even with new studies coming out, that is still going to be an area of interest in my mind.
The other piece is that we still don’t really know which is the most appropriate frontline therapy. Every center has their own treatment, some of which are based on studies, some of which are adapted from studies. I think we still don’t really know how to treat patients with MCL.
Fortunately, the survival is much better than it has been in the past. There still is a ton of variability among oncologists—even oncologists who specialize in lymphoma—as far as how to treat it.
Is there a certain clinical trial going on right now that you feel could answer those questions? If not, is there a certain clinical trial design you feel would help answer those questions? The US Intergroup has two studies that may help contribute somewhat to both of those issues.
First is the EA4151 trial, in which patients—regardless of their induction regimen—undergo minimal residual disease (MRD) assessment. Those who are MRD-negative are randomized to receive a transplant or not receive a transplant.
This research will help us, to some extent, identify populations that still may benefit from transplants versus those that may not.
Then there’s sort of a companion trial, EA4181, that is looking at a couple of different frontline regimens to try to determine how important, for example, cytarabine is. How important is it that patients get a BTK inhibitor?
Those two studies, combined with the TRIANGLE study presented at ASH, hopefully will help us sort through some of those issues. Obviously, there will be more questions and new therapies we want to investigate. But I’m hopeful these studies will help us at least continue to move toward an answer.
What do you hope to see happen in the field? What do you think can happen in the next five to 10 years? It would be great to be better at identifying which patients need which therapy. It may be, for example, that some patients really need cytarabine, a BTK inhibitor, and transplant. Whereas others may need none of those or just one of those.
Being able to better tailor therapy would be great. It will help patients, and it will help us make sure that we’re doing things properly.
The other thing we haven’t talked as much about is that there is a population that, despite all those interventions, still experiences early relapse. Those patients, unfortunately, tend to have a shorter survival.
I’ve been very interested in a number of ongoing studies looking at moving CAR-T, for example, earlier on in the course of therapy, especially for high-risk patients, and integrating bispecific antibodies for some of the high-risk patients.
There are some newer therapies that are either here or emerging that may positively impact outcomes for patients with high-risk disease. I’d love to get to a place where even high-risk patients are able to get their disease under control and enjoy a prolonged survival.
What would you want to tell someone who is just starting out in the field of hematologic oncology? The key is to try to latch on to a mentor who is both clinically strong and interested in helping you get involved with research. That is critical. It’s a small community, but all of oncology is becoming more complicated, especially malignant hematology. It really is exploding with the number of new therapies and classifications. Having somebody who you can rely on, who is going to help you gain that clinical expertise, and who is going to look out for research opportunities is important. Mentorship is important in any field, but I think in malignant hematology especially, it’s critical.
The other piece is recognizing that there’s a lot we still don’t understand and that it’s okay to ask questions. I send out questions to some of my colleagues regularly—even though I’ve been doing this now for a while—because it seems like every month you see something you’ve never encountered before. The key is to surround yourself with a good support team.
It’s important to recognize that it’s an ever-evolving field and understand that the right thing to do in November 2022 may not be the right thing to do in March 2023. Things change pretty rapidly.
What are some of your favorite hobbies and activities outside of work? I have three kids who are all school age, so a lot of our time outside of work is going to sporting events and school activities. As a family, we really enjoy travel. My wife and I have had the opportunity to do a bit of exploring. We love the beach, so we’ve been to a number of beaches here in the Southeast, and we’ve also been to Europe a couple times.
We also are pretty big sports fans. We like to go to Braves games here in Atlanta. My two older kids are particularly into it.
My wife and I also enjoy trying new restaurants. She’s a more adventurous eater than I am, but we still try to check out new things when we can.
As you can imagine, the work can sometimes be very intense; then other times, fortunately, there’s a bit of time to relax or take a break. When we do have those free evenings or afternoons, we try to take advantage of it.
Is there a skill you have or something that people might be surprised to learn about you? I can’t really claim it as an active skill, but one thing people may not know is that I participated in the National Spelling Bee as a teenager. I placed 21st in the country, which was exciting. I still am a decent speller, but I certainly don’t retain those nationally ranked spelling skills.
As an adult, I developed a talent for baking. In the last couple years during COVID-19, I started doing some baking, and that has been enjoyable. Probably my favorite thing I’ve made is an apple pie from scratch. And croissants—with the croissants, it’s a two-day process, but it’s incredibly satisfying when those come out good.
Any other thoughts you’d like to share? The key thing that has helped me be successful is that there generally is a lot of cooperation and collaboration within our hematologic malignancy community. I would encourage anybody who is pursuing a clinical career in malignant hematology to avail themselves of the many people who are out there and are happy to help them in their career, whether they’re at the same center or another.
There are a number of folks I’ve called upon over the years to provide help with clinical cases or research projects.
It’s hard and complicated work. There are a lot of complex issues. It’s important to identify that you’re not going to always know exactly what to do and that there are others who may have had that experience and are happy to provide support.
Jonathon Cohen, MD, MS, is an Associate Professor in the Department of Hematology and Medical Oncology at the Emory University School of Medicine.