Dr. Davids on Updated Data With Ibrutinib/Umbralisib in R/R CLL and MCL

Matthew S. Davids, MD, MMSc, an associate director with the Center for Chronic Lymphocytic Leukemia; director of clinical research, Lymphoma Program; and medical oncologist at Dana-Farber Cancer Institute and an assistant professor of medicine at Harvard Medical School, discusses updated findings from a phase 1/1b study which examined the combination of ibrutinib (Imbruvica) and umbralisib in relapsed/refractory chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL).

Initial results from the study were published early last year with just over 2 years of follow-up, says Davids, and they showed high rates of response in CLL and MCL, as well as good tolerability. From that study, the recommended phase 2 dose of umbralisib was identified at 800 mg twice daily in combination with the standard dose of ibrutinib. The challenge with the early report was that the follow-up was fairly short, notes Davids.

The updated data presented during the 2020 European Hematology Association Annual Congress, look specifically at progression-free survival (PFS) and overall survival (OS) in high-risk patients at a longer follow-up of 43.5 months, adds Davids. Another aspect of the study was the rate of complete remission, which increased over time, something that is often seen with B-cell receptor pathway inhibitors, says Davids.

The PFS and OS data didn't change too much in the patients with MCL, according to Davids. The median PFS in the high-risk patient population was 10.8 months and the median OS was 30.7 months. Thus, the data observed with the combination of ibrutinib and umbralisib did not differ too much from ibrutinib monotherapy. Although the outcomes with the combination were not worse, it is difficult to say whether there is a difference in benefit with this approach versus the monotherapy in this patient population, concludes Davids.