Development of targeted therapies for B-cell non-Hodgkin lymphoma and multiple myeloma.

The design of innovative, more effective, and less toxic therapy of B-cell lymphoma is emerging in parallel to a better understanding of the mechanisms of action of target-specific agents targeting the neoplastic B cell. Rituximab has changed the treatment paradigm of patients with B-cell lymphomas and is considered the first effective targeted therapy approved by the US Food and Drug Administration (FDA) for the treatment of lymphoproliferative disorders. Despite its good efficacy and safety profile, sustained complete remissions have been documented in a relatively small proportion of patients treated with rituximab monotherapy. To improve antitumor activity, initial strategies combined rituximab with standard chemotherapy drugs which led to higher response rates and improvement in disease-free and in some cases (ie, diffuse large B-cell lymphoma) prolongation of overall survival. While rituximab has been incorporated into multiple chemotherapy regimens (ie, CVP, CHOP, FND, etc.) a significant number of lymphoma patients either relapse after initial responses or fail to respond as a consequence of either intrinsic or acquired resistance. Scientific efforts are being focused toward developing new strategies to improve rituximab activity. In this report we provide an overview of recent developments in target-specific therapies and review past, ongoing, and future research tiling this diverse group of exciting novel agents.