James N. Gerson, MD, Assistant Professor of Medicine at Perelman School of Medicine, University of Pennsylvania, Philadelphia, commented on the implications of the findings from CAPTIVATE.

James N. Gerson, MD

“Upfront therapy for chronic lymphocytic leukemia (CLL) is rapidly evolving. We now have three chemotherapy-free regimens that are [U.S. Food and Drug Administration (FDA)]-approved—ibrutinib, acalabrutinib, and the combination of venetoclax and obinutuzumab. Of them, only venetoclax plus obinutuzumab allows time-limited therapy. There is much interest in applying the concept used in many areas of oncology—that combination therapy with different targeted agents will result in deeper and more sustained remissions,” Dr. Gerson said.

“The CAPTIVATE trial is yet another potential step forward. This trial combines ibrutinib and venetoclax in the upfront treatment of CLL. Early data were presented at the ASCO Annual Meeting in 2018 and suggested high rates of minimal residual disease (MRD) negativity in the blood and bone marrow with a manageable toxicity profile. The presentation at the 2019 American Society of Hematology Annual Meeting provided an update and confirmed high rates of MRD negativity after 12 cycles in both blood and bone marrow. The toxicity profile was again shown to be manageable, without the development of new or unexpected adverse events,” he continued.

“The data are compelling, but not yet practice-changing. Longer follow-up, as well as a randomized comparison, is needed prior to FDA approval of this combination as a front-line regimen for patients with CLL. It remains uncertain whether ibrutinib plus venetoclax will lead to superior outcomes as compared to ibrutinib alone, acalabrutinib alone, or venetoclax plus obinutuzumab. Regardless, it is certain that more and more chemotherapy-free regimens are on the horizon, many of which will utilize time-limited therapy and will be associated with high rates of MRD negativity. This is wonderful news for our patients,” Dr. Gerson said. 

DISCLOSURE: Dr. Gerson has served in a consulting or advisory role for AbbVie, Pharmacyclics, and Seattle Genetics.