Dr. Ghobrial, of the Dana-Farber Cancer Institute, discusses how she entered the field of smoldering myeloma, the PCROWD and PROMISE studies, and the racial gap in myeloma research, treatment, and diagnosis.
Where did you grow up and when did you know you wanted to be a physician-scientist?
I’m from Egypt originally, but I grew up in Nigeria. I lived there for 13 years before I moved back to Cairo. My parents are both physicians; my mom is a hematopathologist, and my dad is a cardiologist. For a long time, I did not want to be a physician. Then, as I was going through the process of applying to universities, I realized I was interested in biology, science, and medicine after all. I applied reluctantly, but I think it was one of the best decisions of my life. Immediately after, I knew I wanted to come to the United States to expand my knowledge and reach a different skill level.
I finished medical school in Cairo, went to Canada for a quick observership, and then came to the United States for my residency fellowship. That residency was mainly through the Detroit Medical Center and it was all clinical, so I wasn’t exposed to research. I did a short rotation in immunology with a lab at the Mayo Clinic. There, I learned to do Western blots and similar processes. I remember once at 3 am running six gels simultaneously. They were leaking, and I was stressed out. I said, “This is as bad as the intensive care unit [ICU] rotations we have in medicine.” My colleagues laughed and said, “How could this be as bad as being in the ICU all night?”
The work was exhilarating and stressful, but the best part was asking questions and answering them myself. In medicine, we see patients. We’re taught to do our differential, to do this or that, to give this medicine. But you can never say, “Let me actually ask the question and answer it myself,” which is the part of research I love. I never truly trained as a PhD, although I would have loved to. Instead, I learned science as I was doing it. I’m still learning every day from my postdocs and everyone I work with.
Were there any particular mentors who shaped your career path?
You can’t really become who you are unless you have amazing mentors. My mom was my first mentor. She’s a strong woman who really wanted to excel in everything. She had a PhD when she was living in Egypt, and that’s very rare. She’s a clinician. She raised four girls, and she never made us think we were any different than boys.
Sometimes you have to go out and find your mentors. They won’t come to you. I had great mentors during residency and fellowship. Morie Gertz, MD; Rafael Fonseca, MD; and Robert Kyle, MD—who started the whole world of monoclonal gammopathy of unknown significance (MGUS) and smoldering myeloma—shaped my career. They got me into myeloma and sparked my love for the field.
I also credit Rob Soiffer, MD. I’m a full professor, at a point in my career where a mentor may not be necessary, and yet I go to him all the time, even with the smallest things. It’s a lifetime mentorship. Even a full professor needs someone to talk to, to ask for advice, to look to for an answer to the question, “Am I doing the right thing?”
I would also say my husband; he’s just amazing to believe in me. He believes I can succeed despite everything, and that’s special.
How did you become interested in hematologic oncology, MGUS, and smoldering multiple myeloma?
I started my training with a fellowship at the Mayo Clinic. Thanks to Dr. Kyle, myeloma is a very strong field of study at Mayo. He really created the whole program. He is also an amazing person. He takes the time to explain things and always tells us to take care of the patients and put them first.
Drs. Gertz and Fonseca gave me the strength of understanding I needed to be a good clinician and scientist. They also taught me how to write grants and mentor new people. I still talk to them both; they are lifetime mentors.
I got into this field because of the passion Drs. Kyle, Gertz, and Fonseca have for myeloma. They’re also the reason I like myeloma so much.
Can you explain the PCROWD and PROMISE studies and what’s next for your research?
PCROWD sought to better understand the precursor conditions rather than waiting for MGUS and smoldering myeloma to develop. At the molecular level, what is the mechanism of disease progression? How can we define who will progress and who will not? Dr. Kyle defined it at the clinical and epidemiological levels, but there’s so much more to understand.
We didn’t have samples, and we didn’t see enough patients at Dana-Farber to create cohorts and longitudinal follow-up. We established the Center for Prevention of Progression (now called the Center for Early Detection and Interception of Blood Cancers) and started seeing patients with MGUS and smoldering myeloma. Now, patients from the United States and around the world come to see us. We have expanded into CHIP, monoclonal
B-cell lymphocytosis, and other disciplines. We have cardiologists, neurologists, and social workers on staff. We have developed multiple clinical trials, including a chimeric antigen receptor T-cell trial for smoldering myeloma that is actively recruiting.
For tissue banking, because you need the samples to ask those questions, we said, “Instead of waiting for patients to come to Dana-Farber, let’s have it available for them everywhere.” We put it online. Patients can click a link on a website, we send them a kit, and they send us their blood samples and clinical data. More than 3,000 patients follow us on MGUS and smoldering myeloma, and we have over 10,000 samples in the bank. We’ve been able to perform single-cell RNA sequencing on over 500 samples and whole genome sequencing on hundreds. It’s amazing what patients can do. They can drive research. They can ask the questions we are sometimes afraid to ask. I love collaborating directly with patients.
PROMISE came along because of a Stand Up to Cancer Dream Team application. We asked, “Instead of waiting for people to have MGUS and smoldering myeloma and then diagnosing them, can we screen for it? If you’re at risk, especially if you’re a Black patient, why are you at risk?” We screen only people who are at risk, so this is not a nationwide study where we’re screening the general population.
PROMISE is helping us build an understanding of epidemiology, biology, and genetic variants. It opened the door for so many things, and it continues to open the door, because we have amazing collaborations. We expanded to South Africa and are hoping to expand to Kenya, Rwanda, and other countries. PROMISE brings communities together. It facilitates talking to people and understanding how we can overcome racial barriers. I never thought I would do global health, but I am, and it’s wonderful.
What do you hope to see happen in this field and line of research in the next decade?
Early detection and interception are critical for changing the way we think of cancer. There’s nothing good about metastatic disease in any cancer. Myeloma is the perfect model of a cancer that you can detect early and intercept. You can understand all those steps and use them as a footprint for getting into other cancers in the future.
If we can make it in myeloma, if we can prove that you can change survival, then it can be done in other cancers that might be harder to detect than just a simple blood sample with a monoclonal protein. We’re very lucky to have some tools that can be useful. It’s harder in other cancers. You can’t detect it early, or you can’t find the evidence of it.
I’d love to see us work on equity and diversity. We all say it, but we need to do it. Myeloma is much more common in Black individuals, but we don’t know why. We haven’t really done in-depth germline assessments. We don’t know how the immune system of a Black patient compares with the immune system of a White patient or patients of other races. We don’t know how to close the gap in treatment. Black patients are diagnosed much later than White patients, and we need to change that.
What inspiration or recommendations would you give to younger physicians or trainees in the field?
First, think of what you want. Your own vision is critical. A lot of young faculty members are given a lot of ideas, and they don’t have the time to think or ask themselves, “What do I want in five and 10 years?” They’ll hear, “Oh, write this book chapter. Write this review. Do this clinical trial.” They will get bombarded and need to learn early on to say, “No, I will focus on this question,” and hopefully their mentorship committee will help them. Then, every step is a building block toward that goal.
Second, dream big. Don’t let things limit what you want to do. Think of big ideas, talk to people outside of your community. Mentors may not be in the same area or at the same university. Working with others is important when you’re trying to make a really big dream happen.
Third is a thing I haven’t done, which is find work-life balance. I think it’s critical these days to learn that it’s okay to stop, think a little bit, take time off, and recharge rather than the “go, go, go” that I do.
What hobbies or activities do you enjoy outside of work?
I love to learn and try new things. I’ve taken a lot of hiking trips—I’ve done Kilimanjaro, I did Mount Fuji with my daughter, and I’m hoping to do Machu Picchu. I’m a horrible hiker, and I’m scared of heights, but I enjoy those trips because they alter your life. You spend seven days hiking, no TV, no phone, nothing. You really learn to appreciate life and understand the person you’re hiking with.
I also love running. I’ve done the Boston Marathon and the New York Marathon, and I’m hoping to do a few others. I’m learning Spanish. I’m trying to learn dancing with my husband. I love traveling because I want to learn about other cultures and see the world. I would not mind learning anything and everything if I can.
Irene Ghobrial, MD, is a Professor at the Dana-Farber Cancer Institute and Harvard Medical School.