Matthew S. Davids, MD, MMSc, an associate director with the Center for Chronic Lymphocytic Leukemia; director of clinical research, Lymphoma Program; and medical oncologist, Dana-Farber Cancer Institute; and an assistant professor of medicine at Harvard Medical School, discusses the potential utility of moving the combination of ibrutinib (Imbruvica) and umbralisib into the frontline setting of chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL).

Findings from a phase 1/1b study presented during the 2020 European Hematology Association Annual Congress showed that ibrutinib/umbralisib elicited high response rates in CLL and MCL with a tolerable safety profile.

Updated data from the study revealed that progression-free survival and overall survival did not differ significantly from ibrutinib monotherapy in patients with MCL; however, outcomes were not negatively impacted.

In CLL specifically, the combination may have utility in the post-venetoclax (Venclexta) patient population as venetoclax is being used earlier in treatment, explains Davids.

Moving PI3K inhibitors into the frontline setting has been met with some challenges such as increased immune-mediated toxicities, says Davids.

As umbralisib appears to be a well-tolerated PI3K inhibitor, this combination may have potential utility in CLL, concludes Davids.