Luspatercept Achieved Durable Improved Hemoglobin Levels and Reduced Transfusion Burden in Participants With Lower-Risk MDS

By Blood Cancers Today Staff Writers - Last Updated: December 11, 2024

In participants with lower-risk myelodysplastic syndromes (MDS), luspatercept treatment facilitated hemoglobin levels of 10 g/dL or higher and reduced transfusion dependency, as the phase 3 COMMANDS trial showed. Dose escalation improved hemoglobin levels without significantly increasing the incidence or severity of adverse events, supporting the clinical benefits of dose escalation in this population.

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Luspatercept, a novel erythroid maturation agent, has been evaluated as a first-line alternative to erythropoiesis-stimulating agents for patients with lower-risk MDS dependent on red blood cell transfusions. Following up on that finding, Valeria Santini, MD, University of Florence Medical School, Italy, and colleagues investigated whether luspatercept could help these patients maintain hemoglobin levels while reducing transfusion requirements in the phase 3 COMMANDS trial (NCT03682536).1

Participants with a diagnosis of very low–, low-, or intermediate-risk MDS and transfusion dependency were randomly assigned 1:1 to receive subcutaneous luspatercept at a starting dose of 1.0 mg/kg (with titration up to 1.75 mg/kg) every 3 weeks or epoetin alfa (450 IU/kg, titration up to 1,050 IU/kg and a maximum dose of 80,000 IU).

Of the 182 patients treated with luspatercept, 139 achieved red blood cell transfusion independence lasting 12 weeks or longer; 77.7% of these responders also maintained a mean hemoglobin level of 10 g/dL or higher. For responders, the median duration of their longest and cumulative response was not reached at the data cutoff, highlighting the durability of the response. The remaining 23.3% of responders not achieving hemoglobin of 10 g/dL or higher still presented with a median response duration of 37 to 41 weeks.

Dose escalation to higher doses was required in most (80.2%) participants. In particular, participants with lower baseline hemoglobin levels (<8 g/dL) were likely to require higher luspatercept doses (1.75 mg/kg). Approximately 50% of the participants who achieved hemoglobin of 10 g/dL or higher at the 1 mg/kg dose maintained their target hemoglobin levels through dose escalation to 1.33 and 1.75 mg/kg.

The safety profile of luspatercept remained consistent across all dose levels. Treatment-emergent adverse events (TEAEs) were reported in 97.8% of participants, with grade 3/4 TEAEs in 64.3%. Importantly, the rate and severity of TEAEs, including those related to treatment, did not significantly increase with higher doses.

Overall, luspatercept significantly increased hemoglobin levels and achieved clinically meaningful durable transfusion independence, underscoring the potential longer-term clinical benefits of luspatercept for patients with lower-risk MDS.

REFERENCE

 

Santini V, Zeidan AM, Platzbecker U, et al. Clinical benefits of achieving hemoglobin (Hb) levels ≥ 10 g/dL in transfusion-dependent (TD) erythropoiesis-stimulating agent (ESA)-naive patients (pts) with lower-risk (LR) myelodysplastic syndromes (MDS) treated with luspatercept in the COMMANDS trial. Abstract #1818. Presented at the ASH Annual Meeting; December 7-10, 2024; San Diego, California.

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