Multiple myeloma cells

Front-Line Daratumumab Combo Improves Transplant-Ineligible MM Outcomes

Treatment of newly diagnosed multiple myeloma (MM) is based on risk stratification and eligibility for autologous stem cell transplantation (ASCT). Initial treatment for newly diagnosed multiple myeloma typically includes induction therapy with the combination of a proteasome inhibitor (PI), immunomodulatory drug (IMiD), and dexamethasone, followed by high-dose chemotherapy and ASCT, potentially followed by maintenance therapy. While this approach is highly successful in patients who are eligible to receive transplant, many patients are not transplant eligible due to age or comorbidities. In this population, dose-adjusted IMiDs or PI-based combinations, including bortezomib, melphalan, and prednisone (VMP), are the preferred treatment option. The CD38-targeting monoclonal antibody daratumumab is an approved treatment for relapsed/refractory MM when given in combination with an IMiD or PI, based on high response rates and improvements in progression-free survival (PFS) in the CASTOR and POLLUX trials. Several trials are currently investigating the potential for daratumumab in the front-line setting.

At the 2017 American Society of Hematology (ASH) Annual Meeting, MarÍa-Victoria Mateos, MD, PhD (University Hospital of Salamanca, Salamanca, Spain), presented results from the phase III ALCYONE trial (N = 706), which investigated the combination of daratumumab and VMP compared to VMP alone in newly diagnosed patients with multiple myeloma who were not eligible for ASCT.

The addition of daratumumab to VMP significantly improved PFS, resulting in a 50% reduction in the risk of progression or death compared to VMP (not reached vs 18.1 months; HR 0.5, P<.0001). PFS was superior in all subgroups, including in patients ≥75 years of age, ISS disease stage III, renal impairment, or high-risk cytogenic profile. The overall response rate (ORR) was significantly higher in patients receiving daratumumab (90.9% vs 73.9%; P<.0001). This included an almost doubled complete response (CR) rate (42.6% vs 24.4%) and tripled rate of minimal residual disease (MRD) negativity (22.3% vs 6.2%). The median overall survival was not reached in either group.

Importantly, combining daratumumab with VMD did not increase overall toxicity. Rates of adverse events (AEs) were similar between the two treatment groups, except for infections (66.8 % daratumumab + VMP vs 48% VMP alone). The most common grade 3/4 treatment-related AEs were neutropenia (39.9% vs 38.7%), thrombocytopenia (34.4% vs 37.6%), anemia (15.9% vs 19.8%), and pneumonia (11.3% vs 4.0%). Infusion-related reactions, primarily of grade 1, were observed in 27.7% of patients receiving daratumumab.

Dr Mateos concluded that these data strongly support the use of daratumumab plus VMP as a new standard of care for transplant-ineligible patients with multiple myeloma. Results from this study were simultaneously published in The New England Journal of Medicine.

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