Dr. Jain on Next Steps for Venetoclax in Relapsed MCL

Preetesh Jain, MD, PhD, clinical fellow in medical oncology at The University of Texas MD Anderson Cancer Center, discusses the next steps for a study examining the efficacy of venetoclax in high risk relapsed mantle cell lymphoma (MCL).

In chronic lymphocytic leukemia (CLL), it is known that BCL-2—based mutations are very significant, says Jain. However, in this study, only 17% of patients had a BCL-2 mutation, suggesting that the pattern of resistance with venetoclax in MCL is distinct from CLL. These findings need further validation in a larger cohort of prospectively collected samples.

Investigators are going to conduct similar types of studies and other ongoing trials with venetoclax (Venclexta) and ibrutinib (Imbruvica) in the frontline setting to understand the pattern of resistance in less heavily pretreated patients. To do this, they will have to look at pretreatment samples, Jain adds. In this study, the pretreatment samples had been collected from patients who had previously been treated with some other agents, such as ibrutinib or chemotherapy. As such, their pretreatment clonal evolution findings were not depictive of what an untreated sample would look like.

Even in poor-risk MCL, the response rate with venetoclax was very impressive, says Jain. These data are very provocative, even though it is a retrospective study with a small number of patients and samples available for whole-exome sequencing. These preliminary findings will lead investigators to study this particular pattern of resistance in a larger number of samples, concludes Jain.