Sequence-dependent synergy of the proteasome inhibitor bortezomib and cytarabine in mantle cell lymphoma.

Single-agent bortezomib, a potent, selective and reversible inhibitor of the 26S proteasome, has demonstrated clinical efficacy in relapsed and refractory mantle cell lymphoma (MCL). Objective response is achieved in up to 45% of the patients; however, complete remission rates are low and duration of response proved to be short. These limitations may be overcome by combining proteasome inhibition with conventional chemotherapy. Here we present two case reports and in vitro data suggesting synergistic efficacy of bortezomib combined with cytarabine in MCL. Interestingly, efficacy in vitro correlated with sequence of treatment, indicating that pretreatment with cytarabine, followed by proteasome inhibition, may be the preferred approach.