Darzalex Combination Granted Priority Review for Myeloma Treatment

The Food and Drug Administration (FDA) granted priority review to the combination use of Darzalex (daratumumab), Velcade (bortezomib), melphalan and prednisone for the treatment of newly diagnosed patients with multiple myeloma who are not eligible for autologous stem cell transplant (ACST).

“The granting of priority review to the submission of daratumumab in front line multiple myeloma is an important step forward toward potentially brining this product to an even larger number of patients in need,” Jan van de Winkel, Ph.D., chief executive officer of Genmab, said in a statement.

The supplemental biologics license application (sBLA) was based on trial data that was presented at the 2017 American Society of Hematology (ASH) Annual Meeting and published in the New England Journal of Medicine. The phase 3 ALCYONE study tested the four-drug combination in the frontline treatment setting for this patient population.

The randomized, open-label study involved 706 newly diagnosed patients with myeloma who are ineligible for ACST. Participants were randomized to nine cycles of Velcade, melphalan and prednisone combined with Darzalex (D-VMP) or VMP alone.

In the Darzalex arm, patients received 16 mg/kg of the drug once weekly for six weeks and then once every three weeks. After nine cycles, patients continued to receive 16 mg/kg of Darzalex once every four weeks until their disease progressed. The primary endpoint was progression-free survival (PFS).

Findings showed that adding Darzalex to the triplet combination caused a 50 percent reduction in the risk of progression or death after a median follow-up time of 16.5 months. Median PFS was 18.1 months in the Darzalex arm, and was not reached in the VMP arm.

The most common all-grade adverse events (AEs) for D-VMP and VMP included neutropenia (49.7 percent vs. 52.5 percent), thrombocytopenia (48.8 percent vs. 52.5 percent), anemia (28 percent vs. 37.6 percent), peripheral sensory neuropathy (28.3 percent vs. 34.2 percent), upper respiratory tract infection (26.3 percent vs. 13.8 percent), diarrhea (23.7 percent vs. 24.6 percent), pyrexia (23.1 percent vs. 20.9 percent) and nausea (20.8 percent vs. 21.5 percent).

The most common grade 3 to 4 AEs, which occurred in at least 10 percent of patients in the D-VMP and VMP arms, were neutropenia (39.9 percent vs. 38.7 percent), thrombocytopenia (34.4 percent vs. 37.6 percent), anemia (15.9 percent vs. 19.8 percent) and pneumonia (11.3 percent vs. 4 percent). Only one patient in each arm discontinued treatment due to pneumonia.