Dr. Jain on Future Research Efforts Examining Venetoclax Resistance Patterns in MCL

Preetesh Jain, MD, PhD, clinical fellow in medical oncology at The University of Texas MD Anderson Cancer Center, discusses research efforts examining resistance patterns with venetoclax (Venclexta) in mantle cell lymphoma (MCL).

The findings from a small prospective study indicated that venetoclax-based therapy was highly effective in patients with high-risk MCL and acquired resistance to the agent was predominantly associated with non–BCL-2 mutations. These findings need further validation in a larger cohort of prospectively collected samples, says Jain. Similar types of analyses in other ongoing trials with venetoclax and ibrutinib (Imbruvica) in the frontline setting are also being conducted to understand the pattern of resistance to the agent in less heavily pretreated patients.

To do this, pretreatment samples will need to be collected and studied. In the phase 1 study, the pretreatment samples had been previously treated with other agents, such as ibrutinib or chemotherapy, making the pretreatment clonal evolution data not indicative of what an untreated sample would look like.

Even in patients with poor-risk MCL, the response rate with venetoclax was very impressive. These findings are very provocative, according to Jain, even though it was a retrospective study that had enrolled a small number of patients with limited samples available for whole-exome sequencing. These are preliminary findings, which will potentially lead to studying this particular pattern of resistance in a larger number of samples, concludes Jain.