A new study findings published in the New England Journal of Medicine have revealed that the novel monoclonal antibody product daratumumab has been propelled to the front line for multiple myeloma treatment. The results show that it also improves outcomes in patients with newly diagnosed multiple myeloma who are ineligible for transplant, when used in combination with triple therapy.
The findings, from the phase 3 ALCYONE trial, show that when daratumumab was added to a regimen of bortezomib, melphalan, and prednisone (D-VMP), there was a 50% lower risk for disease progression or death compared with triple therapy without the antibody.
In this first phase 3 randomized study with a monoclonal antibody in newly diagnosed multiple myeloma, D-VMP also induced significantly deeper responses, including a more than threefold higher minimal residual disease negative rate.
While daratumumab has been studied and approved for use in patients with relapsed/refractory multiple myeloma, this is the first study to look at it as a front-line agent in newly diagnosed patients.
The ALCYONE study is multicenter trial conducted at 25 centers globally in 706 patients with newly diagnosed myeloma who were not considered to be candidates for transplant because of coexisting conditions or because they were 65 years of age or older. The team randomly assigned the patients to VMP or D-VMP.
The primary endpoint was progression-free survival, and secondary endpoints included overall response rate (ORR), rate of very good partial response (VGPR) or better, rate of complete response, rate of minimal residual disease negativity, overall survival, and safety.
At a median follow-up of 16.5 months, the hazard ratio for PFS (D-VMP vs VMP) was 0.50 (P < .0001), which represented a 50% reduction in the risk for progression or death for the D-VMP cohort.
Median PFS was not reached in the D-VMP group vs the VMP group. These findings were consistent across all prespecified subgroups, including age 75 years or older and patients with high-risk cytogenetics.
All secondary endpoints were also significantly higher for D-VMP than for VMP. ORR was 90.9% vs 73.9%, the rate of VGPR or better was 71.1% vs 49.7%, complete response rate was 42.6% vs 24.4%, and rate of minimal residual disease negativity was 22.3% vs 6.2%.
The overall survival data remain immature, but to date 93 patients have died (45 in the D-VMP group and 48 in the VMP group). The most common grade 3/4 treatment emergent adverse events for D-VMP vs VMP were neutropenia, thrombocytopenia, anemia, and pneumonia.
While some patients may prefer drug therapy over a transplant, Dr Chari cautioned that these results do not speak to that issue. "This study will not answer the question of whether quadruple therapy will replace transplant because the population in this study is transplant ineligible," he said. "That study will have to be done, to address the question of quadruple therapy as an alternative to transplant."