Jennifer R. Brown, MD, PhD, was awarded the Michael J. Keating Outstanding Achievement Award, which recognizes a clinician’s significant research contributions to advancing hematologic oncology treatment.
“I’m honored to receive the Michael Keating award,” Dr. Brown said in an interview with SOHO Insider. “I have greatly admired his work and always enjoyed his incisive questions in many meetings that we were at together.”
Dr. Brown, who has been an integral part of the revolution in chronic lymphocytic leukemia (CLL) treatment, serves as the director of the CLL Center of the Division of Hematologic Malignancies at Dana-Farber Cancer Institute, one of the few centers in the United States dedicated to treating and researching CLL. She has published more than 300 scientific papers in blood cancers, the majority of which are focused in CLL research and clinical trials.
Highlights of a distinguished research career
Dr. Brown served as principal investigator on many of the early clinical trials of Bruton’s tyrosine kinase (BTK) and phosphoinositide 3-kinase (Pl3K) inhibitors, leading the clinical development of the first wave of targeted therapies in CLL, including idelalisib and ibrutinib. She then led the charge in developing and trialing the second-generation therapies acalabrutinib and zanubrutinib, taking into account those therapies’ successes and limitations.
The experience of treating some of the first patients with the first-generation therapies, many of whom received numerous prior lines of therapy and were “very, very sick,” was one of Dr. Brown’s most rewarding career moments.
“The disease just sort of melted away before your eyes,” she said. “The opportunity to get those drugs and then see how amazingly they worked—and help people—was gratifying.”
Idelalisib, a PI3K inhibitor, was approved in 2014 by the US FDA, but is rarely used now because of its high toxicity in patients, a problem that Dr. Brown identified and has led the research to understand. (The agency withdrew approval in 2022 in treating follicular lymphoma and small lymphocytic lymphoma, but idelalisib remains available for CLL).
In the early days, Dr. Brown explained, idelalisib was neck and neck with ibrutinib, but in the end, ibrutinib proved to be the more effective therapy. Dr. Brown continues to research idelalisib and the therapeutic family of PI3K inhibitors.
“We have a novel [PI3K therapy] that we’re testing in a combination clinical trial, which we expect to have much less toxicity based on its development to date,” she said.
Another career highlight, Dr. Brown cited her research describing the mutation profile of CLL, which helped clarify how specific mutations shape disease progression and prognosis and how resistance-associated mutations emerge and evolve.
“It was also very exciting to describe the mutation profile of CLL initially, and we’re still working on that,” she said. “We’re also working on the resistance mutations and mechanisms of resistance to pirtobrutinib and to PI3K inhibitors.”
Early in her career, Dr. Brown was intrigued by the disease’s heterogeneity (“it’s not just one disease”) and heritability.
“CLL being the most familial lymphoma was interesting, and the way the cells circulate in the blood facilitates research,” she said. “I was excited when we found that ATM variants are associated with CLL risk and especially when we were able to validate that in our clinical data, which was published in the Journal of Clinical Oncology,” she said.
‘Very well deserved’
Susan O’Brien, MD, who is a SOHO past president and sits on the SOHO Education Committee as sub-committee chair, told SOHO Insider that Dr. Brown’s award is very well-deserved.
“I am very excited to learn that my colleague Jennifer Brown will be honored at SOHO with the Michael J. Keating Outstanding Achievement Award,” Dr. O’Brien said. “Jennifer has made enormous contributions to the field of CLL and helped pioneer many new and important therapies.”
Dr. O’Brien pointed to the ALPINE and AMPLIFY clinical trials, results of which were published in separate articles in The New England Journal of Medicine, as major research accomplishments by Dr. Brown and for the field.
“Dr. Brown was the lead author on the ALPINE trial, which showed that zanubrutinib produced less atrial fibrillation that ibrutinib in a randomized trial in relapsed CLL,” Dr. O’Brien noted. “More recently, she was the lead author on another article describing the results of the AMPLIFY trial, which revealed that the duo of acalabrutinib and venetoclax, or the triplet of those drugs in addition to obinutuzumab, produced longer progression-free survival than seen with chemoimmunotherapy in the frontline therapy of CLL.”
The results from the AMPLIFY trial are expected to lead to FDA approval of these combinations in frontline CLL in 2025, Dr. O’Brien said.
At a crossroads
At present, CLL treatment is at a bit of a crossroads, Dr. Brown observed. BTK and BCL2 inhibitors are effective in treating CLL, but clinicians need to be careful that patients do not develop resistance.
“I think it’s very important to try to avoid patients developing resistance to BTK inhibitors because it changes the biology of the disease and then they get less benefit from other therapies,” she said.
Dr. Brown is also worried that the effectiveness of BTK and BCL2 inhibitors might discourage clinicians from developing new therapies. Fortunately, this is not a problem yet as there are “plenty of drugs coming along,” she noted. “We still need new mechanisms for patients with hard-to-treat CLL,” she said.
Novel combinations of existing therapies, such as the combinations used successfully in the AMPLIFY trial, will also be a source of progress going forward, Dr. Brown said.
“I hope that that [trend] spreads into community practice and into the general [treatment] paradigm for CLL more rapidly now,” she said.
‘Batting your head against a wall’
Despite being highly accomplished and regarded globally as a top CLL expert, Dr. Brown still experiences frustrations.
“Research can be slow, or it can be hard to get grants,” she said. “Sometimes it’s like batting your head against a wall until [the grants] come through.”
Her advice to early-career clinicians? Stay persistent in the face of challenges.
“You may have to submit 10 grants to get your first grant, and it’s always been that way,” she said. “You have to be persistent and be able to take those setbacks in stride and still keep going or find new opportunities.”
Dr. Brown added that these frustrations are outweighed by the psychological rewards of caring for patients.
“Taking care of the patients offers immediate gratification because you can help them on a daily basis,” she observed.
She also participates in relaxing activities outside of work that keep her grounded, including reading, swimming at the beach near her summer house on the south coast of Massachusetts, and taking long walks in exotic locales.
“We’re going to go to the United Kingdom to do Hadrian’s Wall. There’s a long-distance path there,” she said. “Next January, we’re going to Vietnam and Cambodia.”
Deep connections with SOHO
Dr. Brown has deep connections with SOHO, having served on the society’s Steering and Education Committees since 2014, and then as SOHO president in 2022-2023. She said her involvement with SOHO started with an invitation to give a talk at the Annual Meeting.
“I was invited to give a talk, and one thing that I’ve always noticed is that the invitations to speak at SOHO usually include topics that have a provocative question or just a somewhat unusual twist on things,” Dr. Brown explained. “[That] invites people to put the data together in a novel way or present it differently.”
Dr. Brown is the Director of the CLL Center of the Division of Hematologic Malignancies at the Dana-Farber Cancer Institute and the Worthington and Margaret Collette Professor of Medicine in the Field of Hematologic Oncology at Harvard Medical School. She serves on the Steering and Education Committees for SOHO and was the 2022-2023 SOHO president.
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