Multinational phase 3 trial of addition of bortezomib to rituximab-cytarabine-dexamethasone for relapsed or refractory mantle cell lymphoma

The therapy of relapsed or refractory mantle cell lymphoma (R/R MCL) remains a major clinical challenge. A randomized phase 3 trial of the European mantle cell lymphoma network compared bortezomib plus rituximab, high-dose cytarabine, and dexamethasone (B+R-HAD) versus R-HAD alone for R/R MCL. Primary endpoint was time to treatment failure. Median time to treatment failure was 12.0 months with B+H-RAD versus 2.6 months with H-RAD (MIPI-adjusted HR 0.69; p=0.045). Overall and complete response rates were 63% versus 45% (p=0.049) and 42% versus 19% (p=0.0062), respectively. Toxicity was mostly hematological and attributable to the chemotherapy backbone. The authors conclude that bortezomib in combination with chemotherapy can be effective in R/R MCL, and should be evaluated further as a therapeutic option, especially when therapy with BTK inhibitors is not an option.