Dr. Jain on Response and Resistance to Venetoclax in Relapsed/Refractory MCL

Preetesh Jain, MD, PhD, clinical fellow in medical oncology at The University of Texas MD Anderson Cancer Center, discusses response and resistance to venetoclax (Venclexta) in relapsed/refractory mantle cell lymphoma (MCL).

Investigators at The University of Texas MD Anderson Cancer Center conducted a prospective study of 24 patients who received venetoclax-based salvage therapy. These patients were heavily pretreated, having received a median of 5 prior lines of therapy. A few patients had also relapsed after CAR T-cell therapy, says Jain. However, the overall response rate was 50%, suggesting that venetoclax works well in patients with highly refractory disease that has progressed on a BTK inhibitor.

However, patients did progress after receiving venetoclax. These patients have a poor survival of around 6 to 7 months, says Jain. Investigators found a pattern of clonal evolution and increased frequency in histone modifier mutations, such as KM2TD, TP53, and SMARCA4. Additionally, investigators found CELSR3, which has never been identified in MCL before, says Jain.