The Road Ahead for CLL Research and Treatment: Overcoming Challenges and Embracing Innovations in Patient Care

Featuring Jennifer R Brown, MD, PhD 

Please share your name, title, and a brief overview of your professional history. 

Jennifer R Brown, MD, PhD: I’m Jennifer R Brown, MD, PhD, Director of the CLL Center and Institute Physician at Dana-Farber Cancer Institute (DFCI) in Boston and the Worthington and Margaret Collette Professor of Medicine in the field of Hematologic Malignancy at Harvard Medical School.  I trained at Harvard, completed my residency at Massachusetts General Hospital, and did my fellowship at DFCI. Since 2004, I have been faculty at DFCI running my clinical and translational research program in chronic lymphocytic leukemia (CLL).  

How have recent studies or trials shaped the current recommended treatment options for CLL patients, and what implications do these findings have for clinical pathways?

Dr Brown: Over the last 5 to 10 years, we have had many phase 3 trials comparing targeted therapies to chemoimmunotherapy. As a result, targeted therapy has really become the standard of care for frontline CLL. This typically looks like either one year of venetoclax-obinutuzumab or continuous BTK inhibitor.  We have also had phase 3 comparisons of both acalabrutinib and zanubrutinib with ibrutinib. This resulted in demonstrating that the second-generation drugs were shown to be safer, and in the case of zanubrutinib, also more effective, than ibrutinib.  

What challenges or obstacles are currently hindering progress in CLL research and treatment? 

Dr Brown: I think the biggest challenge in CLL research is that relatively few patients enroll on clinical trials and the only way we can learn what therapy is best is through clinical trial enrollment.   

Based on your research, what are the most promising developments in CLL treatment pathways that health care professionals and patients should be aware of in the near future? How do you see the landscape of CLL treatment evolving?

Dr Brown: The newest development is the advent of combinations of BTKis with BCL-2is, which provide an all-oral regimen of typically 1 to 2 years of therapy. The AMPLIFY trial has been announced to be positive by press release and I will present the data at the upcoming American Society of Hematology meeting. It is hoped that those results will lead to the first approval of a second generation BTKi (acalabrutinib) with venetoclax, +/- the antiCD20 antibody obinutuzumab, for the therapy of CLL. This will provide another option for first-line therapy that is entirely oral, well tolerated, and time limited.