Overcoming Rituximab Resistance: The US Clinical Experience With Bendamustine

Despite the wide usage, mild side effect profile, and commendable efficacy of rituximab in frontline treatment of indolent lymphoma, resistance to this agent commonly develops, ultimately limiting patient treatment options. The mechanisms of rituximab resistance have not yet been fully elucidated, although both tumor- and host-associated resistance mechanisms have been proposed. Several strategies for overcoming rituximab resistance are currently being evaluated, including manipulation of the immune system, as well as second-generation engineered anti-CD20 antibodies. Ultimately, the use of novel agents with alternative mechanisms of action may represent the best solution for overcoming rituximab resistance. The cytotoxic chemotherapeutic agent bendamustine, which has both alkylating agent and other cell-killing properties, has been used successfully in phase II clinical trials to treat rituximab-refractory disease. Ongoing pivotal studies are currently evaluating the use of bendamustine in this difficult-to-treat lymphoma patient population.