Dr. Zeidan, Associate Professor of Medicine at Yale University, Director of Early Therapeutics Research in Hematology and Assistant Medical Director of the Clinical Trials Office at Yale Cancer Center, and leader of Myeloid Malignancies and Leukemias DART (Disease Aligned Research Team) at Yale Comprehensive Cancer Center discusses a patient who shaped his career path, what he sees as the most pressing questions in the field, and more.
Where did you grow up, and when did you know that you wanted to be a physician? I grew up in Jordan, my home country. Both of my parents were teachers. In Jordan, many families want their kids to be physicians. It’s a cultural thing. Since I was very young, that was instilled in me. As far as I can remember, I always wanted to be a physician. Initially, when I was a kid, I wanted to be an orthopedic surgeon because my mother suffered from a significant disc prolapse in her spine. However, that quickly changed during medical school when I realized I did not want to be a surgeon.
What led you to specialize in hematologic oncology and myeloid malignancies such as acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) specifically? Medical school in Jordan is six years right after high school. It’s not divided into undergraduate education and then a separate medical school. The first three years are preclinical, and in the fourth year, you start going to the wards, you work with the inpatient teams, and you interact with the patients.
I happened to be placed in the hematology/oncology ward during one of my very early rotations in the fourth year. Seeing those patients with different malignancies was emotional for me, especially a particular patient who was a young kid—I think he was eight or nine years old—with an advanced malignancy called Ewing sarcoma. He was in the hospital for end-of-life care because he had stopped responding to all treatments at that point and the family was unable to take care of him at home.
I saw him every day. He did not have really any sense of what was going on because he was just too young. He would ask me questions like, “When will I be able to go home?” It was very impactful for me. Not only did that experience make me want to be able to help patients with cancer in general, but it also made me want to do clinical research for my career to avoid being at that point where you cannot offer the patients any additional treatment, which is a very difficult situation. Sometimes you cannot fix the underlying disease, but at least you can give patients hope or a fighting chance. Many patients, all they ask for is a fighting chance against their cancer. Doing clinical trials and being able to offer the patient—as long as they want to keep fighting—a new therapy on a clinical trial, a new opportunity to fight the cancer, an opportunity to help future patients with that cancer, and was something I really wanted to do.
That is why I decided to go into hematology/oncology. That is also why I decided to come to the United States, in all honesty, because clinical research, at that time, was quite limited in Jordan. I wanted the best training, not only in my field, but also in clinical research.
In terms of why I focused on myeloid malignancies, that’s something I always enjoyed as a medical student, blood conditions and the hematology syllabus in general. I actually did quite a bit of classical hematology research early in my training on thrombosis, bleeding, and anticoagulation. Some of my early career mentors were focused on those conditions, including Dr. Peter Kouides in Rochester, NY and Dr. Michael Streiff at Johns Hopkins.
Very early in my hematology/oncology fellowship it became clear to me that I wanted to do malignant hematology, in particular leukemia and MDS. That decision was largely driven by my admiration for two of my early mentors at Johns Hopkins, Drs. Steven Gore and Judy Karp.
Can you tell us about some of the research and clinical trials you’re currently working on? Clinically and research-wise, I focus on myeloid malignancies, especially AML and MDS. I’ve been lucky to start my fellowship during an era in which many new and exciting therapies were being studied for both conditions.
I started my first faculty job in 2014 at Yale University, and a number of exciting drugs were going through the pipeline then. Starting in 2017, multiple drugs—a total of 10 drugs—have been since approved for AML after many years of no drug approvals for this very tough-to-treat blood cancer. Two other drugs have been approved for MDS. There has been a lot of development in solid oncology and other blood cancers as well, especially for immunotherapy agents, so it’s been a very exciting area, with many new drugs.
My research has focused on trying to find new therapies or new combinations of therapies for patients with advanced MDS or AML. I focused on immunotherapies to try to help some of those patients.
The second area of research that I do—in addition to clinical trials—is outcomes research, which is population-based, real-life analysis, and effectiveness research. I find it very complementary to my clinical trial work, because often you see good results on clinical trials, but once the drugs get approved, you are not seeing the same degree of success when those drugs are used in the real-life setting. I find my real-life outcomes work helps identify some of these gaps and why the drugs sometimes underperform.
What are some of the most pressing questions in MDS and/or AML that still need to be addressed? I’ll start with MDS, which has two areas that I think need a lot of work. One of those areas is improving the efficacy of hypomethylating agents though combinations with other novel agents, as these drugs are currently approved for management of higher-risk MDS as monotherapies and their single-agent activity remains suboptimal.
Bone marrow transplant is the only potential way to cure MDS. But most patients—more than 90%—are not able to undergo transplant because of their age, medical conditions, lack of donors, and so on, so we are stuck with noncurative treatment for most patients with higher-risk MDS, which is clearly not very satisfying. Trying to optimize the treatment has been a big part of what I do. Adding drugs to the hypomethylating agents so you can continue to improve the overall survival and outcomes is a major area of unmet need.
The second area of unmet need is after those hypomethylating agents stop working. That is what we call a hypomethylating agent failure situation, which is a big problem in the management of patients with higher-risk MDS. The survival is generally less than six months on average when that happens, so it’s very important to try to find therapies in that setting.
In AML, the bigger obstacle is that many patients can go into remission, but many of them will relapse. Trying to get them to a curative situation is very challenging, especially among older patients.
How to use combinations of the multiple new drugs that have been approved and how to sequence them is a very important area of research these days. Of course, it’s also important to find new therapies. Many of the therapies that we have can help patients, but patients are still relapsing and often die from their disease, so we still need to discover new and more effective drugs.
What do you hope to see happen in the field of MDS and AML over the next five to 10 years? I think we are going to continue to go in a positive direction in both diseases. Ideally, we want to have therapies that can increase the number of patients who can be cured. We have had some success at this. We have been able to take more patients to transplant and try to cure them.
Realistically, most patients are older and have multiple medical problems, so transplant is not a practical option for them and often we cannot cure them despite our best efforts. Even when they undergo transplant, the most common reason transplant does not work is because of relapse.
At that point, it’s often very difficult to achieve a cure. We give a lot of treatments with the goal of extending survival. If you cannot cure the cancer, try to maintain or improve quality of life, minimize complications and time spent in clinic or hospital, and optimize things for the patient in a way that aligns with their goals.
For example, we have patients whose goal is to be there in a year for their daughter’s graduation from university or their son’s wedding or their grandchild’s graduation from high school. They know that we cannot cure the disease, but trying to achieve that short-term goal is very meaningful, not only for them, but for their families. Those are smaller victories but can mean a lot for the patients and their families.
We have more and more drugs that are being added in multiple combinations. They are given orally. Historically, we used to treat leukemia with just chemotherapy, which has a lot of side effects, and patients had to be in the hospital. Now, we can do more and more outpatient treatment with multiple drugs given early on and try to optimize the quality of life and extend survival for the patient.
My hope and expectation over the next five to 10 years is that we see more of these combinations, more migration to oral drugs, and more treatment in the outpatient setting. This will allow us to optimize quality of life and give patients the ability to enjoy their lives and families as much as possible, as long as possible, while limiting their time in the hospital and the chances of complications.
You’re quite active on Twitter. Can you speak to how you use social media as a platform to engage with other clinicians and researchers? Twitter is interesting for me. In all honesty, I used to dislike Twitter because of the politics involved and some of the polarization that takes place there. But when the coronavirus pandemic hit, it impacted our ability to interact with a lot of our colleagues. We went into lockdowns and did not have in-person conferences. Twitter gradually became a way for a lot of the medical community to stay in touch and give their opinion about different studies. A significant number of people from the oncology/hematology community have joined the platform.
On a personal level, I enjoy cooking and trying different cuisines from across the world. Twitter has been a way to connect with people who have these same passions. Travel has always been one of my main hobbies, and Twitter has also allowed me to share my experiences.
I do find it professionally helpful. It’s a good way to humanize and meet many of your colleagues when you don’t know much about them on a personal level. Overall, the experience has been good, but I think it has its own advantages and disadvantages, and people have to figure out the best way to use it.
Is there a skill, hobby, or interest you have that people might be surprised to learn about? I have two main hobbies. In addition to traveling, I’m a huge fan of soccer, especially European soccer. My favorite team is a Spanish team called Real Madrid. I have been a hardcore fan of theirs since I was 13 or 14 years old. I have luckily been able to go to several of their big games, including the Champions League finals, which is the equivalent of the Super Bowl. That was one of the most amazing experiences for me.
Amer Zeidan, MBBS, MHS, is the Director of Early Therapeutics Research in Hematology and Assistant Medical Director of the Clinical Trials Office at Yale Cancer Center.
*In the photo at top, Amer Zeidan, MBBS, MHS, is shown while traveling in Cappadocia, Turkey. Photo courtesy of Dr. Zeidan.