The Janssen Pharmaceutical Companies of Johnson & Johnson announced overall survival (OS) results from the Phase 3 ALCYONE study, which showed the addition of DARZALEX® (daratumumab) to bortezomib, melphalan and prednisone (D-VMP) improved OS in patients with newly diagnosed, transplant-ineligible multiple myeloma, with a 40 percent reduction in the risk of death compared to VMP alone. These updated data from the ALCYONE study also demonstrated that the addition of DARZALEX® to VMP resulted in higher rates of minimal residual disease (MRD) negativity.
"As a physician treating patients with multiple myeloma, I want to achieve the deepest response in the frontline setting to hopefully provide long-term benefit," said Maria-Victoria Mateos, M.D., Ph.D., Director of the Myeloma Unit at University Hospital of Salamanca-IBSAL, Salamanca, Spain, and a study investigator. "This longer follow-up from the ALCYONE study is encouraging because we see that adding daratumumab to VMP in the frontline setting can provide an important overall survival advantage compared with a current standard of care."
Results of a prespecified interim analysis, after a median duration of follow-up of more than three years, showed an estimated 42-month OS rate of 75 percent for DARZALEX®-VMP versus 62 percent for VMP, with a statistically significant improvement in OS observed for DARZALEX®-VMP versus VMP alone (hazard ratio [HR]=0.60; 95 percent confidence interval [CI], 0.46-0.80; P=0.0003). Of note, median OS was not assessed in either group and follow-up is ongoing. In addition, DARZALEX®-VMP resulted in a median progression-free survival (PFS) of 36.4 months versus 19.3 months with VMP alone after a median follow-up of 40.1 months (HR=0.42; 95 percent CI, 0.34-0.51; P<0.0001). The results also demonstrated that DARZALEX®-VMP achieved significantly higher rates of MRD-negativity compared to VMP alone (28 percent vs. 7 percent, respectively) at a threshold of one tumor cell per 10-5 white cells.
The most common Grade 3/4 treatment-emergent adverse events (TEAEs) occurring in ≥3 percent for DARZALEX®-VMP arm compared to the VMP arm included neutropenia (40.2 percent vs. 39 percent), thrombocytopenia (34.7 percent vs. 37.9 percent), anemia (17.3 percent vs. 19.8 percent) and pneumonia (13 percent vs. 4.2 percent).1 Grade 5 TEAEs were 6.9 percent in the DARZALEX®-VMP treatment arm compared with 5.6 percent in the VMP arm and discontinuation due to TEAEs was 6.9 percent in the DARZALEX®-VMP arm vs. 9.3 percent in the VMP arm, and the rate of invasive second primary malignancy in the DARZALEX®-VMP vs. VMP treatment arms were 4.9 percent vs. 4.5 percent, respectively.1 No new safety concerns were identified.
Common Grade 3/4 TEAEs occurring in ≥10 percent of patients in the DARZALEX®-Rd arm compared to the Rd arm were neutropenia (51 percent vs. 35 percent), lymphopenia (15 percent vs. 11 percent), pneumonia (15 percent vs. 9 percent), anemia (14 percent vs. 21 percent), leukopenia (11 percent vs. 6 percent) and hypokalemia (10 percent vs. 10 percent), respectively. The most common serious TEAE in the DARZALEX®-Rd arm compared to the Rd arm was pneumonia (14 percent vs. 9 percent, respectively). The most common Grade 3/4 infection rates were 36 percent in the DARZALEX®-Rd treatment arm compared with 27 percent in the Rd arm.2 In the DARZALEX®-Rd arm, 9 percent of patients discontinued treatment due to TEAEs, compared with 18 percent of patients in the Rd arm.
The randomized, open-label, multicenter Phase 3 ALCYONE (MMY3007) study enrolled 706 newly diagnosed patients with multiple myeloma who were ineligible for high-dose chemotherapy with autologous stem cell transplant (ASCT). The median age was 71 years (range: 40-93). Patients were randomized to receive up to nine cycles of either DARZALEX®-VMP or VMP alone. In the DARZALEX®-VMP arm, patients received 16 mg/kg of DARZALEX® once weekly for the first six weeks (Cycle 1), followed by once every three weeks for the next 48 weeks (Cycles 2–9). Following the nine cycles, patients in the DARZALEX®-VMP arm continued to receive 16 mg/kg of DARZALEX® once every four weeks until disease progression.
The randomized, open-label, multicenter Phase 3 study included 737 newly diagnosed patients aged 45-90 years old (median age of 73) with ...
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