FDA Approves Frontline Darzalex/Rd in Transplant-Ineligible Myeloma

The Food and Drug Administration (FDA) has approved the combination of Darzalex (daratumumab) with Revlimid (lenalidomide) and dexamethasone (DRd) for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplantation.

The approval, which was granted through the agency's Real-Time Oncology Review pilot program, is based on findings from the phase 3 MAIA trial, in which Darzalex regimen led to a 44% reduction in the risk of disease progression or death in transplant-ineligible patients with newly diagnosed multiple myeloma who are transplant ineligible versus Revlimid/dexamethasone alone.

In the open-label, multicenter, phase 3 MAIA trial, 737 newly diagnosed patients with multiple myeloma who were ineligible for high-dose chemotherapy and ASCT aged 45 to 90 years old. Patients were randomized to receive either DRd or Rd alone in 28-day cycles. Treatment was administered in both arms until disease progression or unacceptable toxicity. The median age was 73 (with and age range of 45 to 90), and 52% of patients were male and 92% were white.

At a median follow-up of 28 months, results also demonstrated that the median progression-free survival for DRd has not yet been reached compared with 31.9 months for patients who received Rd alone. Moreover, DRd led to deeper responses versus Rd alone, including higher rates of a complete response or better at 48% versus 25%. The overall response rate was also higher with the triplet regimen, at 93% versus 81%, respectively.

"Multiple myeloma can become more difficult to treat after relapse, so it is important that patients receive an efficacious upfront therapy with a goal of extending their first remission period," Saad Usmani, M.D., FACP, Department of Hematologic Oncology and Blood Disorders, Levine Cancer Institute/Carolinas HealthCare System, and a lead investigator of the MAIA study, stated in a press release. "This regimen offers an important frontline treatment option for this patient population, and it has been submitted to the NCCN Multiple Myeloma Panel for review and consideration for potential inclusion in the NCCN Clinical Practice Guidelines."

Regarding safety, the most common serious treatment-related side effects for DRd (greater than or equal to 10%) included neutropenia (5%), lymphopenia (15%), pneumonia (14%) and anemia (12%). Infusion-related reactions occurred in 41% of patients, 3% of which were serious. The safety profile of Darzalex was consistent with what has been reported in prior studies.

The most common serious hematologic side effects in the DRd arm were neutropenia (50% vs 35% with Rd), lymphopenia (15% vs 11%), anemia (12% vs 20%) and thrombocytopenia (7% vs 9%).

The most frequently occurring nonhematologic side effects in the DRd arm included pneumonia (14% vs 8% with Rd); fatigue (8% vs 4%); diarrhea (7% vs 4%); deep vein thrombosis, pulmonary embolism or both (6% in each arm); asthenia (4% in each arm); back pain (3% in each arm); constipation (2% vs less than 1%); peripheral edema (2% vs less than 1%); and nausea (1% vs less than 1%).

This article was adapted from an article that originally appeared on OncLive as "FDA Approves Frontline Daratumumab/Rd in Transplant-Ineligible Myeloma."