daratumumab + cyclophosphamide + bortezomib + lenalidomide + dexamethasone

Dara-CVRd is an intensive five-drug combination regimen consisting of the monoclonal antibody daratumumab, the alkylating agent cyclophosphamide, the proteasome inhibitor bortezomib, the immunomodulatory drug lenalidomide, and the corticosteroid dexamethasone. This regimen is the focus of the OPTIMUM (MUKnine) Phase II trial sponsored by the University of Leeds, which evaluates its efficacy in patients with newly diagnosed ultra-high-risk multiple myeloma or primary plasma cell leukemia. The combination utilizes multiple synergistic mechanisms: daratumumab targets CD38 on plasma cells to induce immune-mediated lysis; lenalidomide binds cereblon (CRBN) to induce the degradation of transcription factors Ikaros and Aiolos; bortezomib inhibits the 26S proteasome to disrupt protein homeostasis; cyclophosphamide causes DNA cross-linking; and dexamethasone modulates glucocorticoid receptor signaling to induce apoptosis. This augmented approach is specifically designed to overcome the poor prognosis associated with high-risk genetic features in plasma cell dyscrasias.

Brand names

DarzalexCytoxanVelcadeRevlimidDecadron

Other names

Dara-VCD-RDara-CVR-DDara-CVRd regimen