As reported in The Lancet by Maria-Victoria Mateos, MD, and colleagues, interim analysis of overall survival in the phase III ALCYONE trial has shown a significant benefit of the addition of daratumumab to bortezomib, melphalan, and prednisone (D-VMP) in patients with newly diagnosed multiple myeloma who are not eligible for autologous stem cell transplantation.
Maria-Victoria Mateos, MD
The previously reported primary analysis of the trial showed significantly prolonged progression-free survival with D-VMP vs VMP alone and supported the May 2018 U.S. Food and Drug Administration approval of daratumumab in combination with VMP in this setting.
Study Details
In the international open-label trial, 706 patients were randomly assigned between February 2015 and July 2016 to receive D-VMP (n = 350) or VMP (n = 356). Patients were ineligible for high-dose chemotherapy with autologous stem cell transplantation on the basis of age ≥ 65 years or the presence of substantial comorbidities.
All patients received up to nine 6-week cycles of subcutaneous bortezomib (1.3 mg/m2 on days 1, 4, 8, 11, 22, 25, 29, and 32 of cycle 1 and on days 1, 8, 22, and 29 of cycles 2 to 9), oral melphalan (9 mg/m2 once daily on days 1 to 4 of each cycle), and oral prednisone (60 mg/m2 once daily on days 1 to 4 of each cycle). Patients in the D-VMP group also received intravenous daratumumab (16 mg/kg once weekly during cycle 1, once every 3 weeks in cycles 2 through 9, and once every 4 weeks thereafter as maintenance therapy until disease progression or unacceptable toxicity).
The current results are from a prespecified interim analysis of overall survival.
Overall Survival
At a median follow-up of 40.1 months, death had occurred in 24% of the D-VMP group vs 35% of the VMP group (hazard ratio [HR] = 0.60, P = .0003). Estimated 36-month survival rates were 78.0% (95% confidence interval [CI] = 73.2%–82.0%) vs 67.9% (95% CI = 62.6%–72.6%). Follow-up for overall survival is ongoing.
KEY POINTS
- At a median follow-up of 40.1 months, death had occurred in 24% of the D-VMP group vs 35% of the VMP group.
- Median overall survival was 36.4 months vs 19.3 months; estimated 36-month rates were 50.7% vs 18.5%.
Updated analysis of progression-free survival showed a continued benefit with D-VMP, with a hazard ratio of 0.42 (P < .0001). Median overall survival was 36.4 months vs 19.3 months; estimated 36-month rates were 50.7% vs 18.5%.
Safety Profile
The most common adverse events of any grade during daratumumab maintenance were respiratory infections—including upper respiratory tract infections in 19% of patients, bronchitis in 15%, viral upper respiratory tract infections in 12%, and cough in 12%—and diarrhea (10%). The most common grade 3 or 4 adverse events during daratumumab maintenance were anemia (4%), pneumonia (4%), hypertension (3%), neutropenia (2%), and thrombocytopenia (2%).
The investigators concluded, “D-VMP prolonged overall survival in patients with newly diagnosed multiple myeloma who were ineligible for stem cell transplantation. With more than 3 years of follow-up, the D-VMP group continued to show significant improvement in progression-free survival, with no new safety concerns.”
Dr. Mateos, of the Instituto de Investigacion Biomedica de Salamanca, Hospital Universitario de Salamanca, is the corresponding author for The Lancet article.
Disclosure: The study was funded by Janssen Research & Development. For full disclosures of the study authors, visit thelancet.com.
