Breakthroughs Start with Strong Patient Relationships

Many healthcare professionals get into medicine out of a desire to help people, and Zachary Epstein-Peterson, MD of Memorial Sloan Kettering Cancer Center, is no exception. In fact, one of the primary factors that led him to focus his career on lymphoma was witnessing the close relationships between doctor and patient during his early rotations, and it’s those deep connections with patients that continue to inform his lymphoma research today.

Dr. Epstein-Peterson began considering a career in oncology during his first experiences working with cancer patients at Harvard Medical School. After observing both exceptional patient care and opportunities for research
advancements, he continued to seek out opportunities in oncology during his residency at the University of
Washington, New York-Presbyterian Weill Cornell Medical Center, and finally Memorial Sloan Kettering, where he was propelled forward by several mentors.

“The intensity of the relationship between doctor and patient is unique to oncology,” said Dr. Epstein-Peterson.
“While in residency at different oncology clinics at Memorial Sloan Kettering, I saw almost every patient bring a gift to the Clinical Director of Lymphoma Outpatient Services during the holidays. That was a bit of an early window, both into the patient population and the clinical issues that arise, and that planted a seed for what the future could hold.”

With lymphoma, in particular, Dr. Epstein-Peterson saw an even greater opportunity to foster those deep patient
relationships due to the often chronic nature of the disease and the intense treatments with which it is associated. He was fortunate to continue his training in his home state of New York at Memorial Sloan Kettering with a fellowship in Hematology and Medical Oncology before being hired as an attending physician in January 2022. “Even since I started, I’ve already seen some patients 10 to 15 times,” he said. “The critical diagnosis and the sheer volume of visits means that I’m going to get to know my patients and their families and caretakers really well.”

In his practice, Dr. Epstein-Peterson sees and treats every type of lymphoma, but he has a particular interest in T-cell lymphomas and mantle cell lymphoma (MCL). He recognized during his training that these sub-types face “a major unmet need” because of their rarity and complexity. “I routinely see patients who need better therapies, more effective therapies, and better-tolerated therapies, so there’s more work we need to do,” said Dr. Epstein-Peterson. One of his mentors, Steven M. Horwitz, MD – an LRF Scientific Advisory Board (SAB) member and lymphoma oncologist at Memorial Sloan Kettering – also contributed to Dr. Epstein-Peterson’s decision to specialize. “To be able to work with him, an international expert in this area, and to have his mentorship and guidance along the way, was a slam dunk,” Dr. Epstein-Peterson added.

Improving Patient Care Through Research

At Memorial Sloan Kettering, Dr. Epstein-Peterson sees patients two days per week in the clinic and spends the other three days handling administrative work, research, and other follow-up clinical issues. In his limited spare time, Dr. Epstein-Peterson enjoys being with family, exploring the outdoors to the extent possible in Manhattan, and listening to classical music and jazz. He also likes to travel and follows the commercial aviation industry, “a little bit nerdily,” by his own admission.

Dr. Epstein-Peterson applies this same enthusiasm to his work. One of his current research projects is investigating if isocitrate dehydrogenase 2 (IDH2) enzyme inhibitors can treat angioimmunoblastic T-cell lymphoma (AITL). IDH2 mutations have been identified in a subgroup of patients with this rare form of non-Hodgkin lymphoma (NHL), and there are drugs successfully targeting that mutation in other cancers. “But there aren’t really any targeted therapies that are specific to mutations for patients with T-cell lymphomas yet, so if we’re able to show that this treatment is safe and effective, it would hopefully be a major advance forward for molecularly targeted therapies,” said Dr. Epstein-Peterson.

In the laboratory, Dr. Epstein-Peterson is trying to understand even more about how and why this form of AITL develops, specifically the different cells that occur in the cancer and how they interact with each other. “The hope would be that somehow we uncover new avenues for treatments by understanding the tumor better,” he said. He is also researching another innovative treatment avenue, a form of therapy called EZH2. As an epigenetic enzyme, EZH2 controls which genes are expressed or not expressed in the cell, and he says there’s recently been promising data for a medication that inhibits that enzyme. He’s starting to look now to understand how that medication actually works and why some patients don’t respond to it.

Dr. Epstein-Peterson’s research ideas already stand out in the field. He received the Lymphoma Research Foundation’s (LRF) Clinical Investigator Career Development Award in 2022, for the clinical trial he’s getting off the ground at Memorial Sloan Kettering to test the IDH2 inhibitor for AITL patients. Receiving this award was “a tremendous honor” for Dr. Epstein-Peterson. “I was really humbled and thankful for the recognition,” he says. “It was a validation of some of the work that I’ve done with my mentors. They put a lot of wind in the sails to keep pressing forward, because grant success is few and far between in academic medicine.” Dr. Epstein-Peterson’s completed research is already garnering industry recognition, too. A major journal recently accepted his publication of the high-level results of a clinical trial for a new mantle cell lymphoma treatment approach that was designed and implemented at Memorial Sloan Kettering, mentored by Dr. Anita Kumar, herself a prior LRF Career Development Award recipient.

Dr. Epstein-Peterson is also involved in several other clinical trials still taking place. Building upon earlier work done at Memorial Sloan Kettering that found one way of targeting a signal transducer and activator of transcription (STAT) pathway showed benefits for T-cell lymphoma patients, he the Memorial Sloan Kettering head of the multicenter clinical trial which is looking at a different way to target that pathway. He’s also involved in another multicenter study on the use of chimeric antigen receptor (CAR) T-cell therapy in mantle cell lymphoma and is helping to lead a similar effort that will look at the benefits of this therapy. The goal, he says, is to first “understand the patients who clearly seem to really benefit the most from CAR T-cell therapy and then those who unfortunately didn’t benefit as much.” That insight may optimize their patient selection for this treatment moving forward. “If there’s a certain feature or something that shows patients aren’t going to respond as well, then we should understand why that is, and that may inform future efforts there,” he added.

When Dr. Epstein-Peterson looks at a research problem, he first thinks of his patients. “Whatever problem we’re working on, I wish that whatever advances come of this were available for a certain patient in the past, who maybe we weren’t able to save. I think about the patient I’m treating right now – maybe somehow this can help them in the future,” he said. On the flip side, the clinical issues he sees arise in his patients’ care directly feed into the research problems he wants to address. For instance, he’s noticed that patients with AITL can sometimes have Epstein Barr Virus (EBV) at the same time – raising questions about that virus’ relationship to the cancer and possible therapy options. “Seeing that in patients that you’re taking care of and looking at that in the biopsy specimen, it then directly feeds into more basic science or translational questions to try to understand it. I think there’s a lot of synergy for seeing patients and being a researcher,” Dr. Epstein-Peterson said.

The Road to a Cure

Looking at the future of lymphoma research, Dr. Epstein-Peterson sees a lot to be excited about. For one, the field is becoming even more collaborative. “More and more, I see institutions partnering together, and working together to try to design trials,” he said. “In the past, things were a little bit more siloed. But even in the past couple of years, I’ve seen even more collaboration occurring over time. That can only benefit researchers and patients because some of these are rare conditions, and you really need a lot of people together to try to study them.”

Dr. Epstein-Peterson is also optimistic about the “explosion of immunotherapy as another research frontier. “Having new approaches that are completely different, that work in a different way and have different mechanisms is really important and exciting,” he explained. “I think it opens up new avenues for treatment that may benefit people in the future where chemotherapy either doesn’t work or has side effects.”

Always thinking about what will benefit patients most, Dr. Epstein-Peterson believes efforts to deescalate therapy and incorporate patient-reported outcomes (PROs) into clinical trials – two things that have been done in other cancer types – could show a lot of promise for lymphoma treatments in the future. He also highlights the growing recognition that healthcare disparities across underrepresented patient populations need to be addressed, stemming from lymphoma research that shows certain racial and ethnic groups may have inferior treatment outcomes. “We want to be equitable, and we want every patient to have the best chance. So, trying to understand those patterns, I think there’s a growing interest within the field,” he said. “Then the next step after that will be interventions to level the playing field and try to address some of those disparities within the field as much as possible.”

To reiterate why greater investment in lymphoma research is needed, Dr. Epstein-Peterson points to the importance of finding safer therapies without toxicities as well as more palliative therapies that better mitigate side effects and symptoms of the disease itself, like the itching that can be common in cutaneous (skin) lymphoma. He also emphasizes how the chronic nature of some lymphomas presents another challenge. “If we have ‘X’ number of tools in the toolbelt, eventually, we’re going to really need to build on that, especially for younger patients who have a whole lifespan ahead of them to deal with this chronic illness,” Dr. Epstein-Peterson said. “We know that over time, as patients go through therapy after therapy, eventually the cancer just starts outsmarting things. For that reason, we need more tools in the toolbelt.”

Despite these needs, funding isn’t as robust for lymphoma compared to other cancer types. Dr. Epstein-Peterson explains this is because lymphoma patients tend to do better than other types of cancers that are even harder to treat, and that epidemiologically, other cancers are a bit more common as well. It can also be harder to do research for the much rarer lymphoma sub-types since it costs more to conduct clinical trials at multiple centers. “But we’re still seeing patients everyday who need our help, and we’re trying to advance the field forward. LRF and other organizations like it have a unique and needed role to fill that gap and to provide funding where it may not otherwise be present,” he said.

Funding to Support the Lymphoma Community

When Dr. Epstein-Peterson was a fellow at Memorial Sloan Kettering, another one of his mentors, David J.
Straus, MD, invited him to give a presentation about marginal zone lymphoma at one of the Lymphoma Research Foundation’s (LRF) scientific meetings. “I was immediately impressed,” Dr. Epstein-Peterson said about this first encounter with LRF. He believes LRF’s sole focus on lymphoma provides a unique opportunity to drive its mission.

Ever since Dr. Epstein-Peterson has continued to stay close to the organization. In addition to receiving one
of LRF’s Career Development Awards in 2022, he was named an LRF Scholar in 2021 as part of the Lymphoma
Scientific Research Mentoring Program (LSRMP). The funding he’s garnered through that program has been
helpful for conferences, training, and hardware purchases to jumpstart his career, he says. “The fact that they really promote early career investigators, networking, and career development, I think is extremely important because that’s not always possible through traditional funding mechanisms or through other opportunities.”

Dr. Epstein-Peterson also emphasizes how LRF’s initiatives benefit not only researchers but also patients directly. “Having patients participate in clinical trials is a very tangible way to move the field forward. I know that LRF has a lot of efforts in that regard to help patients find trials,” he said. He adds that patient advocacy also goes a long way. “Anything that patients or caregivers or families can do to advocate for more funding for lymphoma research and more awareness of lymphoma as an issue, can only benefit them and benefit us as researchers to get more attention, and ultimately, more funding for what we want to accomplish.”

“I think it’s fundamental for ultimately achieving more cures and developing better therapies that we have
organizations like LRF to get us there,” said Dr. Epstein- Peterson. “The efforts that they support, I have every
expectation, will majorly benefit patients in the future from many perspectives: new therapies, better therapies,
better side effects, better ways to understand the patient experience. All of that will help patients in the future for sure.”