May 08, 2018—Yesterday, the U.S. Food and Drug Administration (FDA) approved the use of the CD38-directed antibody daratumumab for the treatment of newly diagnosed patients with multiple myeloma who are ineligible for autologous stem cell transplant (ASCT). Daratumumab was approved in combination with the proteasome inhibitor bortezomib, the alkylating agent melphalan, and the corticosteroid prednisone (VMP).

Daratumumab has been previously approved as monotherapy, for the treatment of patients with multiple myeloma following at least 3 prior lines of therapy (including a proteasome inhibitor and an immunomodulator agent); in combination with pomalidomide and dexamethasone for patients who have received at least 2 prior lines of therapy (including lenalidomide and a proteasome inhibitor); and in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for patients who have received at least 1 prior line of therapy.

Yesterday’s approval is based on results from the randomized, open-label, multicenter phase III ALCYONE trial (NCT02195479) in which 706 patients were randomized to receive VMP alone (N=356) or VMP in combination with daratumumab (N=350). Investigators reported that the objective response rate (ORR) for patients receiving daratumumab was 91% compared with 74% for patients in the control arm, including a complete response or better for 43% and 24% of patients, respectively. Further, the minimal residual disease (MRD) negativity rate was 22% for patients in the experimental arm compared with 6% for patients in the control arm.

At 12 months, 87% of patients in the daratumumab group remained progression-free, compared with 76% of patients in the VMP group. At 18 months, progression-free survival rates were 72% and 50%, respectively. Overall, the addition of daratumumab to VMP reduced the risk of progression or death by 50%.

Adverse events (AEs) most commonly observed in patients receiving daratumumab included upper respiratory tract infection (48%), infusion reactions (28%) and peripheral edema (21%). Serious AEs included pneumonia (11%), high-grade upper respiratory tract infection (5%), and pulmonary edema (2%). Grade 3/4 hematology AEs included lymphopenia (58%), neutropenia (44%), and thrombocytopenia (38%).

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Jonathan A. Bell
Published Online: Tuesday, May 08, 2018