Maria-Victoria Mateos, MD, PhD
ATLANTA—Study results “strongly support” a new standard of care for transplant-ineligible patients with newly diagnosed multiple myeloma (MM), according to a speaker at the 2017 ASH Annual Meeting.
The study, ALCYONE, suggests treatment with bortezomib, melphalan, and prednisone (VMP) can be improved by the addition of daratumumab (D).
D-VMP produced deeper responses and prolonged progression-free survival (PFS) when compared to VMP.
“In this first phase 3, randomized study with a monoclonal antibody in newly diagnosed multiple myeloma, daratumumab reduced the risk of progression or death by 50%,” said Maria-Victoria Mateos, MD, PhD, of University Hospital of Salamanca in Spain.
“No new safety signals were observed [with D-VMP], except for higher infectious events that resolved. I would say the results of this study strongly support daratumumab in combination with VMP as a standard of care in transplant-ineligible, newly diagnosed multiple myeloma.”
Dr Mateos presented results from ALCYONE as a late-breaking abstract (LBA-4) at the ASH Annual Meeting. The study was simultaneously published in NEJM. The research was supported by Janssen Research and Development.
Patients and treatment
ALCYONE enrolled 706 patients with newly diagnosed MM who were not eligible for high-dose chemotherapy with autologous stem cell transplant.
Patients were randomized to receive VMP or D-VMP. They were stratified by International Staging System (I, II, III), region (Europe vs other), and age (<75 vs ≥75 years).
All patients received up to 9 cycles of VMP:
- Bortezomib at 1.3 mg/m2 twice weekly on weeks 1, 2, 4, and 5 of cycle 1 and once weekly on weeks 1, 2, 4, and 5 of cycles 2 through 9
- Melphalan at 9 mg/m2 once daily on days 1 to 4 of each cycle
- Prednisone at 60 mg/m2 once daily on days 1 to 4 of each cycle.
Patients in the daratumumab arm received the drug at 16 mg/kg once-weekly for the first cycle, every 3 weeks for cycles 2 to 9, and every 4 weeks thereafter, until disease progression. These patients also received dexamethasone (to manage infusion reactions) at 20 mg on the same schedule.
Baseline characteristics were similar between the VMP (n=356) and D-VMP (n=350) arms. The median age was 71 in both arms (range, 50-91 in the VMP arm and 40-93 in the D-VMP arm). Males made up 47% of the VMP arm and 46% of the D-VMP arm.
Forty-nine percent of patients in the VMP arm and 52% in the D-VMP arm had an ECOG performance status of 1. Twenty-eight percent and 22%, respectively, had a status of 0.
The median follow-up was 16.5 months (range, 0.1-28.1). At the clinical cutoff date (June 12, 2017), 5% of patients in the VMP arm were still on study treatment, as were 71% of patients in the D-VMP arm.
Response and survival
“I would like to note that the benefit of the addition of daratumumab was observed since the beginning of the treatment,” Dr Mateos said.
The overall response rate was 74% in the VMP arm and 91% in the D-VMP arm (P<0.0001). The median duration of response was 21.3 months in the VMP arm and was not reached in the D-VMP arm.
The rate of complete response was 24% in the VMP arm and 43% in the D-VMP arm (P<0.0001). Six percent of patients in the VMP arm and 22% in the D-VMP arm were negative for minimal residual disease (P<0.0001).
The hazard ratio for disease progression or death in the D-VMP arm versus the VMP arm was 0.50 (P<0.0001).
The median PFS was 18.1 months in the VMP arm and was not reached in the D-VMP arm. The 12-month PFS was 76% and 87%, respectively. And the 18-month PFS was 50% and 72%, respectively.
D-VMP prolonged PFS regardless of patient sex, age, cytogenetic risk, ECOG performance status, baseline renal function, and other factors.
The median overall survival was not reached in either treatment arm. There were 48 deaths in the VMP arm and 45 in the D-VMP arm.
Adverse events
The most common treatment-emergent adverse events (TEAEs; in the D-VMP and VMP arms, respectively) were neutropenia (50% and 53%), thrombocytopenia (49% and 54%), anemia (28% and 38%), peripheral sensory neuropathy (28% and 34%), upper respiratory tract infection (26% and 14%), diarrhea (24% and 25%), pyrexia (23% and 21%), and nausea (21% and 22%).
The most common grade 3/4 TEAEs (in the D-VMP and VMP arms, respectively) were neutropenia (40% and 39%), thrombocytopenia (34% and 38%), and anemia (16% and 20%).
There were 6 deaths due to TEAEs in the D-VMP arm and 5 such deaths in the VMP arm.
The rate of grade 3/4 infections was higher in the D-VMP arm than the VMP arm—23% and 15%, respectively. The most common of these was pneumonia, with rates of 11% and 4%, respectively.
Infections resolved in 88% of cases in the D-VMP arm and 87% of cases in the VMP arm. Rates of treatment discontinuation due to infection were 0.9% and 1.4%, respectively. One patient in each group stopped treatment due to pneumonia.
Twenty-eight percent of patients in the D-VMP arm had infusion-related reactions (15% grade 3 and 2% grade 4). Most of these reactions occurred during the first infusion. Five patients (1.4%) discontinued daratumumab due to infusion-related reactions.
