Luspatercept Elicits Enduring Benefit in Lower-Risk MDS Population

Luspatercept-aamt (Reblozyl) demonstrated durable activity among patients with lower-risk myelodysplastic syndrome (LR-MDS) who may require transfusions, according to findings from the phase 3b MAXILUS trial (NCT06045689) presented at the 2026 European Hematology Association (EHA) Congress.

Among patients without prior exposure to erythropoiesis-stimulating agent (ESAs; n = 54), red blood cell transfusion independence (RBC-TI) for at least 8 weeks plus concurrent hemoglobin (Hb) increase of at least 1 g/dL was observed in 81.5%. Additionally, 83.3% had RBC-TI for at least 8 weeks, 75.9% had RBC-TI for at least 12 weeks, 72.2% had RBC-TI for at least 12 weeks plus concurrent Hb increase of at least 1.5 g/dL, and 87.0% experienced modified erythroid hematologic improvement (mHI-E).

In a subgroup analysis across the ESA-naive cohort, 73.9% of those with ring sideroblast (RS)–negative status, 77.4% of those with RS-positive status, 86.0% of those with serum erythropoietin (sEPO) of less than 200 IU/L, and 36.4% of those with sEPO of more than 200 IU/L achieved RBC-TI for at least 12 weeks. In the ESA-naive cohort, the median peak Hb was 11.3 g/dL (IQR, 9.9-12.4) within 24 weeks of treatment, and the median change from baseline to maximum Hb value of 3.2 g/dL (IQR, 2.5-4.1).

Regarding patients with relapsed/refractory disease following prior ESAs (n = 52), 61.5% experienced RBC-TI for at least 8 weeks plus concurrent Hb increase of 1 g/dL or higher. Additionally, 67.3% had RBC-TI for at least 8 weeks, 50.0% had RBC-TI for at least 12 weeks, 40.4% had RBC-TI for at least 12 weeks plus concurrent Hb increase of at least 1.5 g/dL, and 76.9% experienced mHI-E.

Across patients with relapsed/refractory disease, 36.8% of those with RS-negative status, 57.6% of those with RS-positive status, 56.5% of those with sEPO of no more than 200 IU/L, and 44.8% of those with sEPO exceeding 200 IU/L experienced RBC-TI for 12 weeks or longer. Furthermore, the median peak Hb in this cohort was 9.8 g/dL (IQR, 8.9-10.7) within 24 weeks of therapy, and the median change from baseline to maximum Hb value was 2.4 g/dL (IQR, 1.6-3.5).

“The primary results from the MAXILUS trial confirmed the clinical benefit of luspatercept in first-line [LR-MDS] with severe anemia…and affirm the importance of early treatment initiation with generally well tolerated and efficacious outcomes following luspatercept treatment at a maximum approved dose,” study investigator Matteo Giovanni Della Porta, of Cancer Center IRCCS Humanitas Research Hospital in Milan, Italy, and Humanitas University in Milan, Italy, stated in the presentation.

In the open-label phase 3b MAXILUS study, patients with ESA-naive or ESA-relapsed/refractory/intolerant MDS were assigned to receive luspatercept at 1.75 mg/kg subcutaneously every 3 weeks. After a response evaluation at 24 weeks, patients discontinued therapy if there was no clinical benefit or progression per International Working Group (IWG) criteria or continued treatment for up to 2 years if a clinical benefit was observed. Up to 24 weeks after the final dose of luspatercept, investigators followed up with patients for transfusion collection, progression to acute myeloid leukemia (AML), other malignancies, subsequent MDS therapy, and overall survival (OS).

The trial’s primary end point was RBC-TI for 8 weeks or longer with a concurrent mean Hb increase of at least 1 g/dL. Secondary end points included RBC-TI for at least 8 weeks, RBC-TI for at least 12 weeks, mHI-E per IWG 2018 guidelines, disease progression to AML, and safety. Other analyses focused on duration of RBC-TI for at least 12 weeks and RBC-TI for at least 12 weeks with a concurrent mean Hb increase of 1.5 g/dL. Patients 18 years and older with an MDS diagnosis per WHO 2018 guidelines; IPSS-R very low-, low-, or intermediate-risk disease; a baseline Hb of no more than 10 g/dL, and an ECOG performance status of 0 to 2 were eligible for enrollment.

Across the ESA-naive and ESA-relapsed/refractory/intolerant groups, the median age was 76.0 years (IQR, 71.0-80.0) and 76.0 years (IQR, 70.5-81.5), respectively. Of note, the median time since original MDS diagnosis was 2.2 months (IQR, 0.3-9.2) and 25.2 months (IQR, 10.0-65.5), 70.4% and 48.1% of patients had a transfusion burden category of less than 4, 77.8% and 44.2% had a sEPO level of less than 200 IU/L, and 42.6% and 36.5% had RS-negative status.

In the ESA-naive and ESA-relapsed/refractory/intolerant populations, 70.4% and 38.5% of patients were still on therapy at the time of analysis. Additionally, 33.3% and 3.8% of patients in each group experienced dose delays due to a predose Hb level of 12 g/dL or higher, and 18.5% and 3.8% experienced dose reductions due to Hb increases of at least 2 g/dL compared with previous doses.

Any-grade treatment-emergent adverse effects (TEAEs) occurred in 94.4% of the ESA-naive group and 100% of the ESA-relapsed/refractory/intolerant group, which included grade 3/4 events in 68.5% vs 53.8% of patients. Four patients in the ESA-relapsed/refractory/intolerant group experienced grade 5 TEAEs. Treatment-emergent events of interest in each arm included asthenia (16.7% vs 36.5%), fractures (13.0% vs 11.5%), and hypertension (11.1% vs 13.5%).

Disclosures: Della Porta noted serving as a consultant or having an advisory role with AbbVie, Bristol Myers Squibb, and GSK.

Reference

Della Porta MG, Campelo MD, Santini V, et al. Luspatercept initiated at the maximum-approved dose in patients with lower-risk myelodysplastic syndromes who require transfusions: primary analysis from MAXILUS. Presented at: 2026 European Hematology Association Congress; June 11-14, 2026; Stockholm, Sweden. Abstract S173.