Transfusion Burden Decrease, Hemoglobin Increase With Luspatercept vs Epoetin Alfa Treatment for ESA‑Naive Patients With Transfusion‑Dependent Lower‑Risk MDS

An Additional Analysis from the COMMANDS Study 

Treatment with luspatercept demonstrated efficacy for erythropoiesis-stimulating agent (ESA)-naive patients with transfusion-dependent lower-risk myelodysplastic syndromes (MDS), including clinical benefits such as durable hemoglobin increases and transfusion-burden decreases, versus treatment with epoetin alfa, according to an analysis presented at the Society of Hematologic Oncology (SOHO) 2023 Annual Meeting in Houston, Texas. 

“The COMMANDS study demonstrated durable red blood cell transfusion independence improvements with luspatercept versus epoetin alfa in ESA-naive patients with transfusion-dependent lower-risk myelodysplastic syndromes,” wrote Rami S. Komrokji, MD, Moffitt Cancer Center, Tampa, Florida, and colleagues.

With this additional analysis, the study authors sought to observe and report additional benefits in hemoglobin increase ≥1.5 grams per deciliter (g/dL), red blood cell transfusion independence ≥12 weeks, transfusion-burden reduction, and luspatercept dosing observed from the COMMANDS study. The primary end point was red blood cell transfusion independence ≥12 weeks with concurrent mean hemoglobin increase ≥1.5 g/dL (weeks 1 to 24). Additional end points included response, duration of response, and TB reduction. Study authors noted that greater proportions of luspatercept than epoetin alfa patients achieved mean hemoglobin increase ≥1.5 g/dL (106 [72.1%] vs 75 [48.7%] patients; P <0.0001; in weeks 1 to 24) and red blood cell transfusion independence ≥12 weeks (98 [66.7%] vs 71 [46.1%] patients; P = 0.0002; week 1 to EOT).

The preplanned interim analysis included data from 301 transfusion-dependent adult patients with serum erythropoietin <500 U/L. Patients were randomized to receive subcutaneous luspatercept or epoetin alfa for ≥24 weeks. At the time of interim analysis, 86 out of 147 (58.5%) luspatercept and 48 out of 154 (31.2%) epoetin alfa patients achieved the primary endpoint (P <0.0001). 

The median duration of longest hemoglobin increase of ≥1.5 g/dL (77.9 vs 55.6 weeks), and the median duration of red blood cell transfusion independence of ≥12 weeks (126.6 vs 77.0 weeks), was longer with luspatercept than epoetin alfa. A greater proportion of luspatercept than epoetin alfa patients achieved ≥50% reduction in packed red blood cell units at ≥12 weeks (120 [81.6%] vs 101 [65.6%]; P = 0.0016). The median (95% confidence interval [CI]) duration of transfusion-burden reduction was 130.0 (120.9 to not evaluable [NE]) weeks for luspatercept patients versus 86.9 (47.9 to NE) weeks for epoetin alfa patients. 

A similar number of patients in this analysis escalated the dose (125/178 [70.2%] luspatercept vs 131/176 [74.4%] epoetin alfa patients); 122 (68.5%) luspatercept patients escalated from 1.0 to 1.33 mg/kg, 88 (49.4%) from 1.33 to 1.75 mg/kg; 129 (73.3%) epoetin alfa patients escalated from 450 to 787.5 IU/kg, 102 (58.0%) from 787.5 to 1050 IU/kg.

“Luspatercept demonstrated clinical benefit beyond [red blood cell transfusion independence], including durable hemoglobin increases and [transfusion-burden] decreases, with dose increases consistent with previous studies, shown for the first time in an ESA-naive patient population,” concluded Dr Komrokji and colleagues, “Luspatercept may represent a new standard of treatment for ESA-naive patients with [transfusion-dependent] [lower-risk] MDS.”

Sources:

Komrokji RS, Platzbecker U, Della Porta M, et al. Reduction of transfusion burden (TB), hemoglobin increase, and dose titration in the COMMANDS study of luspatercept versus epoetin alfa (EA) in erythropoietin‑stimulating agent (ESA)‑naive patients with transfusion‑dependent (TD) lower‑risk myelodysplastic syndromes (LR‑MDS). Presented at 2023 SOHO Annual Meeting; September 6-9, 2023; Houston, TX. Abstract MDS-234

Platzbecker U, Della Porta M G, Santini V, et al. Efficacy and safety of luspatercept versus epoetin alfa in erythropoiesis-stimulating agent-naive, transfusion-dependent, lower-risk myelodysplastic syndromes (COMMANDS): interim analysis of a phase 3, open-label, randomised controlled trial. The Lancet. Published June 10, 2023. doi: 10.1016/S0140-6736(23)00874-7