In patients with transplant-ineligible, newly diagnosed multiple myeloma, adding daratumumab to bortezomib, melphalan, and prednisone (D-VMP) continues to improve overall survival (OS) and progression-free survival (PFS) when compared with bortezomib, melphalan, and prednisone (VMP) alone. These data come from long-term follow-up of the phase 3 ALCYONE trial, presented by Maria-Victoria Mateos, MD, PhD, at the 2019 ASH Annual Meeting. These findings confirm the OS benefit of adding daratumumab to standard of care in newly diagnosed, transplant-ineligible patients, the investigators reported.
“For the first time, we demonstrate that the addition of daratumumab to bortezomib, melphalan, and prednisone prolongs overall survival in patients with transplant- ineligible newly diagnosed multiple myeloma, with a 40% reduction in the risk of death versus [bortezomib, melphalan, and prednisone] alone, after a median follow- up of 40 months,” said Dr Mateos, from University Hospital of Salamanca/IBSAL, Salamanca, Spain.
After a median follow-up of over 40 months, updated survival data showed a median PFS of 36.4 months and 19.3 months with D-VMP and VMP, respectively. Median OS was not reached in either group, but a significant benefit for OS was observed with D-VMP versus VMP alone, with an estimated 42-month OS rate of 75% versus 62%. Follow-up is ongoing.
According to the investigators, these results, together with previously reported results from the phase 3 MAIA study, continue to support the addition of daratumumab to frontline treatment regimens in patients with transplant-ineligible, newly diagnosed multiple myeloma. Data from the MAIA study established the benefit of adding daratumumab to lenalidomide and dexamethasone in the frontline treatment of these patients.
Responses to D-VMP Deepen Over Time
The ALCYONE trial randomized 706 patients from 25 countries to either D-VMP (n = 350) or VMP (n = 356). Eligible patients had newly diagnosed multiple myeloma and were ineligible for high-dose chemotherapy and autologous stem cell transplantation due to age (≥65 years) or comorbidities.
The median age was 71 years, and the majority of patients had an Eastern Cooperative Oncology Group performance status of 0-1, meaning they could perform most or all of the physical tasks they were able to perform before their diagnosis. In the D-VMP arm, 20% of patients were International Staging System stage I, 40% were stage II, and 41% were stage III, whereas 17% were classified as having high cytogenetic risk. In the VMP arm, 19% were stage I, 45% were stage II, and 36% were stage III, with 15% classified as high cytogenetic risk.
Overall response rates did not change from primary analysis and remained at 91% in the D-VMP arm and 74% in the VMP arm at updated analysis. However, the quality of responses deepened over time, with 46% of patients achieving complete response at 40 months, compared with 43% at 16.5 months, Dr Mateos reported.
Patients who received D-VMP also had significantly higher rates of minimal residual disease (MRD) negativity, meaning no evidence of myeloma cells was detected after treatment. MRD rates were 28% versus 7% at the time of the updated analysis.
According to Dr Mateos, MRD-negative patients saw significantly improved PFS and OS regardless of which drug combination they were given, but MRD negativity was more sustained with D-VMP, with 14% of patients still MRD negative at 1 year compared with 3% in the VMP arm.
“When we evaluated the proportion of patients who achieved MRD negativity at the primary as well as at the updated analysis, D-VMP was always superior to VMP,” she said.
Median time to subsequent therapy was not reached in the D-VMP group, and was 25.9 months in the VMP group. The investigators observed no new safety concerns, and rates of discontinuation due to treatmentrelated adverse events were lower in the D-VMP group than in the VMP group at 6.9% and 9.3%, respectively.
“This first report of an OS benefit with daratumumab continues to support the use of daratumumab-containing regimens for the treatment of patients with multiple myeloma,” Dr Mateos reported.