COMMANDS Trial in Transfusion-Dependent, Erythropoiesis-Stimulating Agent–Naïve Patients With Very Low-, Low-, or Intermediate-Risk MDS: Multilineage and Safety Results

Patients with lower-risk myelodysplastic syndromes (MDS) often experience anemia as the primary cytopenia. However, it is important to consider the presence of other concurrent cytopenias, as they can impact treatment approaches and overall outcomes. The FDA recently approved using luspatercept to treat anemia in erythropoiesis-stimulating agent (ESA)-naïve adults with lower-risk MDS who may require red blood cell (RBC) transfusions.

This investigation aimed to assess the influence of luspatercept on the development of erythroid, neutrophil, and platelet lineages and its safety in patients with transfusion-dependent, ESA-naïve, lower-risk MDS participating in the COMMANDS trial (NCT03682536).

Patients aged ≥18 years who had lower-risk MDS with or without ring sideroblasts, as well as <5% bone marrow blasts and endogenous serum erythropoietin levels <500 U/L, were included in this study. These patients required regular RBC transfusions (2-6 units every 8 weeks) for ≥8 weeks before randomization and had not received any ESA.

The patients received either luspatercept (1.0-1.75 mg/kg) subcutaneously (SQ) once every 3 weeks or epoetin alfa (450-1050 IU/kg) SQ once weekly for approximately 24 weeks. The assessments conducted during the study included achieving hematologic improvement-erythroid (HI-E), hematologic improvement-neutrophil (HI-N), and hematologic improvement-platelet (HI-P) according to the International Working Group 2006 criteria, the time to achieve HI-E, transfusion requirements before and during treatment, and safety evaluations.

A total of 182 patients were randomized to luspatercept and 181 to epoetin alfa. During weeks 1 to 24, HI-E was attained by 74.2% of patients treated with luspatercept and 53.0% of patients treated with epoetin alfa (P<.0001). The mean time to HI-E was shorter in patients receiving luspatercept than those receiving epoetin alfa (15.5 days vs 25.1 days). The baseline median absolute neutrophil count (ANC) was 2.4 × 109/L in the luspatercept arm and 2.3 × 109/L in the epoetin alfa arm. Patients treated with luspatercept (8.2%) and epoetin alfa (8.8%) had neutropenia (defined as ANC <1.0 × 109/L) at baseline.

Among those, 33.3% of patients receiving luspatercept and 25.0% receiving epoetin alfa achieved HI-N. The baseline median platelet count was 230.0 × 109/L in the luspatercept arm and 236.0 × 109/L in the epoetin alfa arm. Patients who received luspatercept (14.3%) and patients who received epoetin alfa (11.0%) had thrombocytopenia at the beginning of the treatment (defined as a platelet count <100 × 109/L). Among those patients, 42.3% in the luspatercept group and 30.0% in the epoetin alfa group achieved a HI-P. During the treatment period, 67.6% of patients treated with luspatercept and 78.5% treated with epoetin alfa received RBC transfusions (compared with all patients at the beginning of the treatment). Additionally, 6 patients in each group received platelet transfusions (compared with none at the beginning of the treatment). From week 1 to week 24, all grades of treatment-emergent neutropenia were reported in 7.1% and 7.8% of patients in the luspatercept group and epoetin alfa group, respectively. Thrombocytopenia (all grades) was reported in 6.6% of patients receiving luspatercept and 2.8% receiving epoetin alfa.

A higher percentage of patients who received luspatercept achieved HI-E than those treated with epoetin alfa. Although only a small number of patients were eligible for HI-P and HI-N assessments based on the study’s entry criteria, more patients receiving luspatercept achieved HI-P and HI-N responses during the study duration compared with those receiving epoetin alfa. Luspatercept demonstrated significant enhancements in the production of RBCs, neutrophils, and platelets, indicating its effectiveness in treating patients with ESA-naïve transfusion-dependent lower-risk MDS.

Source: Garcia-Manero G, Porta MGD, Santini V, et al. Multilineage and safety results from the COMMANDS trial in transfusion-dependent, erythropoiesis-stimulating agent-naïve patients with very low-, low-, or intermediate-risk myelodysplastic syndromes. Madrid, Spain, & online: presented at EHA2024 Hybrid Congress; abstract P768.