Efficacy of Luspatercept for the Treatment of Transfusion-Dependent, Erythropoiesis-Stimulating Agent–Naïve Patients With Very Low-, Low-, or Intermediate-Risk MDS in the COMMANDS Trial

There is a gap in successful treatment options that offer long-lasting advantages for patients suffering from anemia caused by lower-risk myelodysplastic syndromes (LRMDS). This study presents significant clinical improvements in response to luspatercept treatment among transfusion-dependent, erythropoiesis-stimulating agent (ESA)-naive patients with LRMDS in the COMMANDS trial.

The COMMANDS trial is a phase 3, multicenter, open-label, randomized controlled trial (NCT03682536). Patients who met the following criteria were considered eligible for the study: ≥18 years of age; Revised International Prognostic Scoring System (IPSS-R)-defined very low-, low-, or intermediate-risk myelodysplastic syndromes with <5% bone marrow blasts; had endogenous serum erythropoietin levels <500 U/L; required regular red blood cell (RBC) transfusions (defined as 2-6 RBC units every 8 weeks for ≥8 weeks before randomization); and had not previously received any ESA.

The patients were randomized 1:1 to receive either subcutaneous luspatercept (1.0-1.75 mg/kg) once every 3 weeks or epoetin alfa (EA; 450-1050 IU/kg) weekly for ≥24 weeks. The study also assessed various clinical benefits, including the achievement and duration of ≥50% reduction in RBC units transfused over a period of ≥12 weeks (from week 1 until the end of treatment), the transfusion burden during the treatment period (from week 1 to week 24), the time to the first transfusion, the achievement of and cumulative duration of episodes of RBC transfusion independence lasting ≥12 weeks, and the average increase in hemoglobin (Hb) levels of ≥1.5 g/dL over the course of weeks 1 to 24.

By the data cutoff of September 22, 2023, a significant percentage of patients had been treated with luspatercept, and EA had reduced the number of RBC units transfused by ≥50% over a period of ≥12 weeks. Specifically, 83.0% of luspatercept-treated patients and 66.9% of EA-treated patients achieved this reduction (P=.0002). The median durations of achieving this reduction were 130.0 weeks for luspatercept and 77.0 weeks for EA (P=.0009).

The median time to first transfusion was 155.0 days (95% confidence interval [CI], 80.0-266.0) for luspatercept compared with 42.0 days (95% CI, 23.0-55.0) for EA patients (P<.0001). Among patients who achieved RBC-transfusion independence (TI) ≥12 weeks (weeks 1-24), 20.1% of luspatercept patients and 16.8% of EA patients achieved ≥2 separate RBC-TI ≥12 weeks response episodes.

The cumulative median duration of all response episodes was 154.7 weeks (95% CI, 118.4-not evaluable) in the luspatercept arm and 91.1 weeks (95% CI, 73.1-123.9) in the EA arm (P=.0016). A mean Hb increase ≥1.5 g/dL over weeks 1 to 24 was achieved by 74.2% of luspatercept patients and 52.5% of EA patients (P<.0001).

Luspatercept demonstrated higher rates of improved Hb levels, decreased transfused RBC units, and sustained RBC-TI responses in patients compared with EA.

These results indicate that luspatercept offers significant clinical benefits, making it the recommended treatment for ESA-naïve patients with LRMDS-related anemia.

Source: Zeidan AM, Platzbecker U, Porta MGD, et al. Clinical benefit of luspatercept treatment in transfusion-dependent, erythropoiesis-stimulating agent-naïve patients with very low-, low-, or intermediate-risk myelodysplastic syndromes in the COMMANDS trial. Chicago, IL, & online: presented at 2024 ASCO Annual Meeting; abstract 6565.