Darzalex + chemotherapy in Phase III ALCYONE study shows overall survival benefit in patients with newly diagnosed multiple myeloma ineligible for transplant- Janssen.

The Janssen Pharmaceutical Companies of Johnson & Johnson announced overall survival (OS) results from the Phase III ALCYONE study (Abstract #859) , 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. These data are the first OS results from the ALCYONE study and were featured during an oral session at the 2019 American Society of Hematology (ASH) Annual Meeting in Orlando. The data were simultaneously published in The Lancet.

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 greater than 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). 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. No new safety concerns were identified.

About the ALCYONE Study : The randomized, open-label, multicenter Phase III 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.

See: "Overall survival with daratumumab, bortezomib, melphalan, and prednisone in newly diagnosed multiple myeloma (ALCYONE): a randomised, open-label, phase 3 trial".-Maria-Victoria Mateos, MD, Prof Michele Cavo, MD, Prof Joan Blade, MD, Prof Meletios A Dimopoulos, MD, Kenshi Suzuki, MD, Prof Andrzej Jakubowiak, MD.et al. Published:December 10, 2019DOI:https://doi.org/10.1016/S0140-6736(19)32956-3.