The majority of patients with newly diagnosed multiple myeloma are treated with a triplet of bortezomib, lenalidomide, and dexamethasone (VRd) induction therapy, followed by transplant and maintenance therapy. However, some patients, in particular the elderly, are ineligible for transplant due to frailty or comorbidities. For these patients, treatment with regimens such as VRd or lenalidomide/dexamethasone (Rd) are the standard of care.
In patients with relapsed/refractory multiple myeloma combination of the CD38-targeting monoclonal antibody daratumumab and Rd demonstrated 63% reduction in the risk of progression or death and a tolerable safety profile in the phase III POLLUX trial. Based on these data daratumumab/Rd combination gained FDA approval for relapsed/refractory myeloma.
At the 2018 American Society for Hematology (ASH) Annual Meeting, Thierry Facon, MD, PhD (Hopital Claude Huriez, Lille, France), presented results from the interim analysis of randomized phase III MAIA trial (N = 737) comparing the combination of daratumumab and Rd (D-Rd) to Rd alone in patients with newly diagnosed multiple myeloma who are ineligible for transplant. The median age of patients included in this study was 73 years. 44% of patients were older than 75 years.
At a median follow-up of 28 months, the daratumumab-containing regimen significantly improved progression-free survival (PFS) compared to Rd alone, resulting in a 44% reduction in the risk of progression or death. The median PFS was not reached in patients receiving D-Rd, compared to 31.9 months in patients receiving Rd (HR 0.56, P<.0001). The 30-month PFS rates were 71% and 56% with D-Rd and Rd, respectively. The overall response rate (ORR) was significantly higher in patients receiving D-Rd (93% vs 81%; P<.0001), and a greater proportion of patients achieved complete response (CR) with D-Rd (48% vs 25%). Furthermore, significantly more patients achieved minimal residual disease (MRD) negativity on D-Rd (24% vs 7%; P<.0001).
The adverse events (AEs) were consistent with the known toxicity profile of this combination, and no new safety signals were observed. The most common grade 3/4 hematologic treatment-related AEs in patients receiving D-Rd compared to Rd were neutropenia (50% vs 35%), lymphopenia (15% vs 11%), anemia (12% vs 20%), and thrombocytopenia (7% vs 9%). Among nonhematologic grade 3/4 AEs, the incidence of pneumonia (14% vs 8%), fatigue (8% vs 4%), and diarrhea (7% vs 4%) were slightly higher with D-Rd. The rate of infusion reactions with daratumumab was 41%, but only 3% were grade 3/4.
Dr Facon concluded by saying “this study has established D-Rd as a new standard of care for newly diagnosed patients that are ineligible for autologous stem cell transplantation,” citing the significant improvements in PFS, deep responses including MRD negativity, and tolerable safety profile.
For more information about this and other multiple myeloma studies presented during the 2018 ASH meeting, please listen to our prIME Clinical Updates. For updates on the evolving landscape in multiple myeloma, please view our Expert Review on Best Practices for Multiple Myeloma.