Bristol Myers presents primary efficacy, safety analysis of Phase 3 COMMANDS

Bristol Myers Squibb announced updated results from the primary analysis of the Phase 3 COMMANDS trial, comparing Reblozyl versus epoetin alfa for the treatment of anemia in erythropoiesis stimulating agent-naive patients with lower-risk myelodysplastic syndromes who may require red blood cell transfusions. These data are being presented in an oral presentation at the 2023 American Society of Hematology Annual Meeting, from December 9-12. Results from COMMANDS are under review with the European Commission and served as the basis of a priority review approval by the United States Food and Drug Administration in August 2023 for Reblozyl as a treatment for anemia in ESA-naive adult patients with very low- to intermediate-risk MDS who may require regular RBC transfusions. Reblozyl is being developed and commercialized through a global collaboration with Merck as of November 2021. Safety results were consistent with previous MDS studies, and progression to acute myeloid leukemia and total deaths were similar between arms of the study. The most common treatment-emergent adverse events in at least 10% of patients were diarrhea, fatigue, COVID-19, hypertension, dyspnea, nausea, peripheral edema, asthenia, dizziness, anemia, back pain and headache. Rates of reported fatigue and asthenia were shown to decrease over time. In addition to the overall benefit observed in the ITT population, sub-analyses confirmed similar or greater RBC-TI of Reblozyl compared to epoetin alfa regardless of mutational profile, IPSS-M status, ring sideroblast status, transfusion burden and serum erythropoietin level. Duration of RBC-TI favored Reblozyl across all subgroups, including ring sideroblast status. Reblozyl showed favorability over epoetin alfa in various mutational background observed in lower-risk MDS in an analysis of response by mutational burden. An analysis of clonal-hematopoiesis related mutations showed that 85% of patients in the COMMANDS study had at least one CHIP-related mutation. Further, Reblozyl was associated with the downregulation of inflammatory gene signatures and upregulation of anti-inflammatory pathways. In another analysis, Reblozyl was associated with modulation of inflammation and restoration of effective erythropoiesis in bone marrow samples from the COMMANDS study, reinforcing its role in the expansion and maturation of early and late-stage erythroid precursors.