San Diego, CA—Interim analysis of an international phase 3 clinical trial supports the addition of daratumumab (Darzalex) to lenalidomide (Revlimid) and dexamethasone as the new standard of care in patients with newly diagnosed multiple myeloma who are transplant-ineligible.
Data from the MAIA study reveal longer progression-free survival (PFS) in patients randomized to lenalidomide, dexamethasone, and daratumumab compared with lenalidomide and dexamethasone alone, reported Thierry Facon, MD, Professor, Haematology, Lille University Hospital, France, at ASH 2018.
Lenalidomide, dexamethasone, and daratumumab also “induced significantly deeper responses, including a 3-fold higher incidence of minimum residual disease negativity,” said Dr Facon.
The study is one of the first to test the combination of lenalidomide, dexamethasone, and daratumumab with a current standard of care in this patient population. It has also enrolled a much higher proportion of patients aged >75 years than any previous study, Dr Facon said.
Lenalidomide plus dexamethasone had been established as the standard of care on the basis of the pivotal phase 3 FIRST clinical trial of patients with newly diagnosed, transplant-ineligible multiple myeloma. Daratumumab added to this standard of care in patients with relapsed or refractory multiple myeloma or in those with transplant-ineligible newly diagnosed multiple myeloma resulted in a ≥50% reduction in the risk of disease progression or death in 3 previous phase 3 clinical trials.
The MAIA study, conducted in 14 countries, enrolled 737 patients with newly diagnosed multiple myeloma who were deemed ineligible for a stem-cell transplant. The patients’ median age at baseline was 73 years, with 44% aged >75 years. In all, 29% of patients had stage III disease, and 14% of patients had high-risk cytogenetics.
Patients were randomized to lenalidomide and dexamethasone alone or to lenalidomide, dexamethasone, and daratumumab. In the 3-agent arm, daratumumab was given intravenously at 16 mg/kg weekly for the first 2 cycles, every 2 weeks for cycles 3 to 6, and every 4 weeks thereafter. Treatment continued until disease progression or intolerable adverse events.
With a median follow-up of 28 months at the interim analysis, the median PFS, the study’s primary end point, in the 3-agent arm with daratumumab was not reached versus 31.9 months in the lenalidomide and dexamethasone alone arm, representing a 44% improvement in PFS with the addition of daratumumab (P <.0001).
The overall response rate was 93% with daratumumab, lenalidomide, and dexamethasone versus 81% with lenalidomide and dexamethasone alone (P <.0001). The rate of complete response plus stringent complete response was 47.6% with the 3-agent arm versus 24.7% with the 2 agents.
The proportion of patients who had a very good partial response or better—defined as a ≥90% reduction in levels of myeloma protein in the blood and urine–was also significantly better (79.3%) among patients who received lenalidomide, dexamethasone, and daratumumab compared with 53.1% with lenalidomide and dexamethasone alone.
The rates of minimum residual disease (MRD)-negativity by next-generation sequencing were 24% with lenalidomide, dexamethasone, and daratumumab versus 7% with lenalidomide and dexamethasone alone (P <.0001).
“Deeper remissions is a very exciting prospect,” commented Aaron Gerds, MD, MS, Assistant Professor in Medicine (Hematology and Medical Oncology), Cleveland Clinic Taussig Cancer Institute, OH. “Longer follow-up will be absolutely helpful in seeing what these MRD-negative states induce long-term. [Because these are transplant-ineligible patients] the deep remissions might be more meaningful in that case.”
With an ongoing follow-up, a trend toward an improvement in overall survival is favoring the addition of daratumumab to lenalidomide and dexamethasone versus the 2 agents alone (hazard ratio, 0.78; 95% confidence interval, 0.56-1.1).
The safety profile was consistent with findings from previous studies of lenalidomide, dexamethasone, and daratumumab. The rate of infusion-related reactions was 41%, of which only 3% were grade 3 or 4. Neutropenia was more common with lenalidomide, dexamethasone, and daratumumab than with lenalidomide and dexamethasone alone (57% vs 42%, respectively), including grade 3 or 4 (50% vs 35%, respectively).
Among the nonhematologic adverse events, pneumonia was more common in the 3-agent arm versus lenalidomide and dexamethasone alone (23% vs 13%, respectively), including grade 3 or 4 pneumonia (14% vs 8%, respectively).
Treatment-emergent adverse events included 7% deaths with the 3-agent combination versus 6% with lenalidomide and dexamethasone alone. Overall, 19% of patients have died.