Maximum-Dose Luspatercept Produces Durable Transfusion Independence in Lower-Risk Myelodysplastic Syndromes

Clinical Summary:

• Design/Population: The phase 3b MAXILUS study evaluated luspatercept initiated at the maximum approved dose of 1.75 mg/kg in transfusion-dependent patients with lower-risk myelodysplastic syndromes who were either erythropoiesis-stimulating agent (ESA) naïve or ESA relapsed/refractory or intolerant.
• Key Outcomes: Luspatercept produced high rates of sustained red blood cell transfusion independence and erythroid hematologic improvement in both ESA-naïve and ESA-refractory cohorts, including patients with ring sideroblast-negative disease. The safety profile remained consistent with previous studies, with few patients progressing to higher-risk myelodysplastic syndromes and none progressing to acute myeloid leukemia.
• Clinical Relevance: These findings support initiation of luspatercept at the maximum approved dose in transfusion-dependent lower-risk myelodysplastic syndromes and reinforce its established efficacy and safety across both ESA-naïve and ESA-refractory populations.

Results from the phase 3b MAXILUS trial demonstrated that luspatercept initiated at the maximum approved dose produced durable erythroid responses and high rates of transfusion in patients with transfusion-dependent lower-risk myelodysplastic syndromes (MDS), regardless of prior erythropoiesis-stimulating agent (ESA) exposure. 

These results were presented by Matteo Giovanni Della Porta, MD, Cancer Center IRCCS Humanitas Research Hospital, Milan, Italy, at the European Hematology Association (EHA) Congress in Stockholm, Sweden.

In this multicenter, open-label trial, 106 patients with non-del(5q) transfusion-dependent lower-risk MDS received 1.75 mg/kg of subcutaneous luspatercept every 3 weeks. Patients were required to receive at least 1 unit of packed red blood cells within 8 weeks of treatment initiation. Included patients were enrolled into either ESA- naïve (n = 53) or ESA relapsed/refractory or intolerant (n = 53) cohorts. 

The primary end point was red blood cell transfusion independence lasting at least 8 weeks with a concurrent mean hemoglobin increase of at least 1 g/dL during the first 24 weeks of treatment. Key secondary end points included red blood cell transfusion independence lasting at least 8 or 12 weeks, modified erythroid hematologic improvement, and safety.

At a median follow-up was 11.1 months in the ESA-naïve cohort, the primary end point was achieved in 81.1% of patients with a median time to transfusion independence of 1 day. Red blood cell transfusion independence lasting at least 8 weeks and at least 12 weeks was achieved in 83% and 75.5% of patients, respectively, while modified erythroid hematologic improvement occurred in 86.8% of patients. Sustatined transfusion independence lasting at least 12 weeks was achieved by 72.7% of patients with ring sideroblast-negative disease and 85.7% of those with baseline serum erythropoietin of 200 IU/L or less. 

At a median follow-up of 11.6 months in the ESA-relapsed/refractory or intolerant cohort, the primary end point was achieved in 62.3% of patients with a median time to transfusion independence of 2 days. Red blood cell transfusion independence lasting at least 8 weeks and at least 12 weeks was achieved in 67.9% and 50.9% of patients, respectively, while modified erythroid hematologic improvement occurred in 77.4% of patients. Sustained transfusion independence lasting at least 12 weeks occurred in 40% of patients with ring sideroblast-negative disease and 58.3% of patients with baseline serum erythropoietin of 200 IU/L or less, and modified erythroid hematologic improvement was achieved in 77.4% of patients. 

Luspatercept maintained a safety profile consistent with previous experience. Treatment-related adverse events occurred in 30.2% of ESA-naïve patients and 45.3% of ESA relapsed/refractory or intolerant patients, while grade 3/4 treatment-related adverse events occurred in 11.3% and 7.5% of patients, respectively. Progression to higher-risk MDS occurred in 3.8% of patients in each cohort, and no patients progressed to acute myeloid leukemia.

Luspatercept “initiated at 1.75 mg/kg led to high, sustained [primary end point] achievement in both cohorts,” concluded Dr Della Porta. “The MAXILUS primary analysis reinforces the favorable safety and efficacy profile of [luspatercept] at the maximum-approved dose.” 

Source:

Della Porta MG, Campelo MD, Santini V, et al. Luspatercept (Luspa) initiated at the maximum-approved dose in patients (pts) with lower-risk myelodysplastic syndromes (LR-MDS) who require transfusions: Primary analysis from MAXILUS. Presented at EHA Congress. June 11 - June 14, 2026. Stockholm, Sweden. Abstract EHA- 3474.