As reported in The Lancet Oncology by Mateos et al, the final results of the phase III ALCYONE trial showed persistent benefit with the addition of daratumumab to bortezomib, melphalan, and prednisone (D-VMP) in transplant-ineligible patients with newly diagnosed multiple myeloma. The primary analysis of the trial showed that D-VMP significantly improved progression-free survival vs VMP in this setting.
Study Details
In the international open-label trial, 706 patients enrolled between February 2015 and July 2016 were randomly assigned to receive D-VMP (n = 350) or VMP (n = 356). The current analysis presents outcomes at a median follow-up of 86.7 months (interquartile range = 28.5–85.2 months).
Key Findings
Median overall survival was 83.0 months (95% confidence interval [CI] = 72.5 months to not estimable) in the D-VMP group vs 53.6 months (95% CI = 46.3–60.9 months) in the VMP group (hazard ratio [HR] = 0.65, 95% CI = 0.53–0.80, P < .0001).
The rate of measurable residual disease (MRD; threshold of 10-5) was 28% in the D-VMP group vs 7% in the VMP group (odds ratio [OR = 5.23, 95% CI = 3.27–8.36, P < .0001). More patients in the D-VMP group remained MRD-negative for 6 months or longer (16% vs 4%, OR = 4.05, P < .0001) and 12 months or longer (14% vs 3%, OR = 5.63, P < .0001). Median progression-free survival on the next line of therapy was 66.7 months in the D-VMP group vs 42.4 months in the VMP group (HR = 0.56, P < .0001).
Safety
Overall, the most common grade 3 or 4 adverse events in the D-VMP vs VMP group were neutropenia (40% vs 39%), thrombocytopenia (35% vs 38%), and anemia (18% vs 20%). Serious treatment-related adverse events occurred in 21% vs 16% of patients. Death from treatment-related adverse events was reported in five patients (1%) in the D-VMP group (from pneumonia, acute myocardial infarction, neuroendocrine tumor, tumor-lysis syndrome, and acute respiratory failure) and in three patients (1%) in the VMP group (from acute myeloid leukemia, pulmonary embolism, and bacterial pneumonia).
The investigators concluded: “With more than 7 years of follow-up, D-VMP continued to elicit clinical benefits in transplant-ineligible patients with newly diagnosed multiple myeloma, supporting the efficacy and safety of front-line daratumumab-based therapy in this patient population.”
Maria-Victoria Mateos, PhD, of the University Hospital of Salamanca/IBSAL/Cancer Research Center–IBMCC, Salamanca, Spain, is the corresponding author of The Lancet Oncology article.
Disclosure: The study was funded by Janssen Research & Development. For full disclosures of all study authors, visit The Lancet Oncology.
