The FDA has approved the combination of daratumumab with lenalidomide and dexamethasone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplantation.
The FDA has approved the combination of daratumumab (Darzalex) with lenalidomide (Revlimid) and dexamethasone (DRd) for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplantation (ASCT).1
The approval, which was granted through the agency's Real-Time Oncology Review pilot program, is based on findings from the phase III MAIA (MMY3008) trial, in which the daratumumab 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 lenalidomide/dexamethasone alone (HR, 0.56; 95 CI, 0.43-0.73; P <.0001).2,3
"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, MD, 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."
In the open-label, multicenter, phase III MAIA study, 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. In the DRd arm, patients received daratumumab intravenously at 16 mg/kg 16 weekly for cycles 1 to 2, every 2 weeks for cycles 3 to 6, and every 4 weeks for cycle 7 and thereafter; also in this arm, 25 mg of lenalidomide was administered on days 1 to 21 of each 28-day cycle, and dexamethasone at 40 mg once a week for each cycle. Treatment was administered in both arms until disease progression or unacceptable toxicity.
The median age was 73 (range, 45-90), and 52% of patients were male and 92% were white. The ECOG performance status was 0 or 1 for 83% of patients. Per the multiple myeloma international staging system, 27% of patients were stage I, 43% of patients were stage II, and 29% of patients were stage III. Of the total population, cytogenetic risk level could be determined for 642 patients. A total 86% of these patients were standard risk and 14% of these patients were high risk.
At a median follow-up of 28 months, findings showed 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.
Regarding safety, the most common grade 3/4 treatment-emergent adverse events (TEAEs) for DRd (≥10%) included neutropenia (5%), lymphopenia (15%), pneumonia (14%) and anemia (12%). Infusion-related reactions occurred in 41% of patients, 3% of which were grade 3/4. The safety profile of daratumumab was consistent with what has been reported in prior studies.
The most common grade 3/4 hematologic TEAEs 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 TEAEs 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 <1%); peripheral edema (2% vs <1%); and nausea (1% vs ≤1%).
"Today's approval of DARZALEX underscores the significant clinical benefit of this CD38 monoclonal antibody and our efforts to advance treatment paradigms to change the course of the disease," Craig Tendler, MD, vice president, Clinical Development and Global Medical Affairs, Oncology, Janssen Research & Development, LLC, the developer of daratumumab, stated in the press release. "Importantly, this milestone also highlights the efficiency of the FDA's Real-Time Oncology Review process, ensuring that proven treatment regimens, such as DARZALEX plus lenalidomide and dexamethasone, are made available to patients as soon as possible."