COMMANDS: Updated Data for Luspatercept for Treatment of Anemia in ESA-Naïve Patients With Lower-Risk MDS Presented at ASH

Updated results from the primary analysis of the phase 3 COMMANDS trial (NCT03682536), continue to show benefits of luspatercept (Reblozyl) compared with epoetin alfa for treatment of anemia in patients with myelodysplastic syndromes (MDS), among patients not previously treated with erythropoiesis stimulating agents (ESAs) but who may require red blood cell transfusions.

The data were presented December 9, 2023, during the 65th American Society of Hematology Annual Meeting and Exposition in San Diego, California. These results updated the interim analysis presented at the American Society of Clinical Oncology (ASCO), which led to approval for luspatercept for this group of patients in late August.

“These data from the COMMANDS trial, including additional patients and longer follow-up from the data shown at ASCO, confirm the positive outcome of the interim analysis with superior efficacy and durability compared to ESAs and exemplify how [luspatercept] may impact the treatment of anemia related to MDS,” Guillermo Garcia-Manero, MD, lead investigator and Chief of the Section of Myelodysplastic Syndromes at The University of Texas MD Anderson Cancer Center, said in a statement. “Further, beyond the intent-to-treat population, the analysis confirms that [luspatercept] demonstrated clinical benefit across subgroups.”

The treatment is being developed and commercialized through a global collaboration with Merck as of November 2021 and awaits action from the European Commission.

Results. The analysis presented at ASH involved 363 patients randomized 1:1 to receive luspatercept and epoetin alfa. Results presented were from the analysis of the intent-to-treat population, with data cut off March 31, 2023, and a median treatment uration of 51.3 (3–196) and 37.0 (1–202) weeks for luspatercept and epoetin alfa, and a median follow up of 17.2 (1–46) and 16.9 (0–46) months, respectively. The treatment length was approximately 10 weeks longer at this analysis than at the ASCO presentation. Results showed:

• 60.4%, or 110 patients, who received luspatercept vs. 34.8%, or 63 patients receiving epoetin alfa achieved the primary endpoint of being independent from red blood cell transfusions for at least 12 weeks, alongside a mean hemoglobin increase of at least 1.5 g/dL within the first 24 weeks (P < .0001). Only 34.8% or 63 patients in the epoetin alfa group achieved this endpoint.
• Erythroid response increase of at least 8 weeks was achieved by 74.2%, or 135, of the luspatercept patients vs. 53%, or 96 or the epoetin alfa patients (P < .0001).
• Red blood cell transfusion independence of at least 12 weeks was achieved by 68.1%, or 124, of the luspatercept patients vs. 48.6%, or 88 of the epoetin alfa patients (P < .0001).
• Duration of response was 126.6 weeks (99-NE) for luspatercept in patients who achieved transfusion independence for at least 12 weeks (achieved weeks 1-24) compared to 89.7 weeks (61.9-123.9) for epoetin alfa (HR 0.586; 95% CI, .380-.904; P= .0147).

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 patient-reported fatigue and asthenia decreased over time. The share of patients who progressed to acute myeloid leukemia and total deaths were similar between arms of the study.

Subanalyses confirmed patients taking luspatercept had similar or better transfusion independence than those taking epoetin alfa across a range of clinical subgroups, including mutational profile, Molecular International Prognostic Scoring System (IPSS-M) status, ring sideroblast status, transfusion burden and serum erythropoietin (sEPO) level. Duration of transfusion independent favored luspatercept across all subgroups as well, according to the results.

Reference

Garcia-Manero G, Platzbecker U, Santini V, et al. Efficacy and safety of luspatercept versus epoetin alfa in erythropoiesis-stimulating agent (ESA)-naive patients with transfusion-dependent lower-risk myelodysplastic syndromes: full analysis of the COMMANDS trial. Presented at: 65th American Society of Hematology Annual Meeting and Exposition, San Diego, CA: December 9-12, 2023; Abstr 193. https://doi.org/10.1182/blood-2023-178596