Luspatercept-aamt (Reblozyl) initiated at the maximum-approved dose of 1.75 mg/kg demonstrated robust red blood cell transfusion independence (RBC-TI) rates in patients with transfusion-dependent, lower-risk myelodysplastic syndromes (LR-MDS), according to primary analysis data from the phase 3b MAXILUS trial (NCT06045689) presented at the 2026 EHA Congress.1
In the erythropoiesis-stimulating agent (ESA)–naive cohort (n = 54), 81.5% of patients achieved the primary end point of red blood cell transfusion independence (RBC-TI) for at least 8 weeks, with a concurrent mean hemoglobin (Hb) increase of at least 1 g/dL during weeks 1 to 24. In the ESA-relapsed/refractory/intolerant (ESA-R/R/I) cohort (n = 52), 61.5% achieved the same primary end point.
Additionally, among ESA-naive patients, the median duration of RBC-TI was not reached at the time of analysis, with 73.2% remaining in response. In the ESA-R/R/I cohort, the median duration of RBC-TI was 59.6 weeks.
How was the MAXILUS trial designed?
MAXILUS is a phase 3b, open-label, non-randomized, 2-cohort trial evaluating luspatercept initiated at the maximum-approved dose of 1.75 mg/kg administered subcutaneously every 3 weeks in patients with LR-MDS. In August 2023, the FDA approved luspatercept for the treatment of anemia without prior ESA use in adult patients with very low– to intermediate-risk MDS who may require regular RBC transfusions.2
The MAXILUS trial rationale was grounded in real-world data suggesting that incomplete or delayed dose escalation may contribute to suboptimal responses and early discontinuation. In the phase 3 COMMANDS trial (NCT03682536), 80.2% of patients ultimately required dose escalation to target or maintain Hb in the 10 to 12 g/dL range.
Eligible patients for MAXILUS were ESA-naive or ESA-R/R/I adult patients with LR-MDS who required regular transfusions. The primary endpoint was RBC-TI for at least 8 weeks with a concurrent mean Hb increase of at least 1 g/dL during weeks 1 to 24. The primary analysis included all patients who received their first treatment at least 24 weeks before the October 1, 2025, data cutoff. Median follow-up was 11.1 months (interquartile range [IQR], 7.7–13.7) in the ESA-naive cohort and 11.7 months (IQR, 9.2–14.3) in the ESA-R/R/I cohort.
Patients in both cohorts had a median age of 76 years. Baseline median Hb was 8.1 g/dL in the ESA-naive cohort and 7.5 g/dL in the ESA-R/R/I cohort. Baseline median transfusion burden was 2.0 packed red blood cell units per 8 weeks in the ESA-naive cohort and 4.0 units per 8 weeks in the ESA-R/R/I cohort. Ring sideroblast (RS)–positive disease was present in 57.4% and 63.5% of patients in the ESA-naive and ESA-R/R/I cohorts, respectively.
Key Results from the MAXILUS Primary Analysis
- In the ESA-naive cohort, 81.5% of patients achieved the primary endpoint of RBC-TI ≥ 8 weeks with concurrent Hb improvement ≥ 1 g/dL; 75.9% achieved RBC-TI ≥ 12 weeks, with median duration not reached.
- In the ESA-R/R/I cohort, 61.5% met the primary endpoint; 50.0% achieved RBC-TI ≥ 12 weeks, with a median duration of 59.6 weeks.
- The median peak Hb was 11.3 g/dL in ESA-naive patients (median change from baseline, +3.2 g/dL) and 9.8 g/dL in ESA-R/R/I patients (median change, +2.4 g/dL).
- Treatment-related grade 3/4 TEAEs occurred in 11.1% of ESA-naive and 7.7% of ESA-R/R/I patients; there were no treatment-related grade 5 TEAEs in either cohort.
What were the additional efficacy findings?
In the ESA-naive cohort, 75.9% of patients achieved a secondary end point of RBC-TI of at least 12 weeks. Results were consistent across clinically relevant subgroups, with 73.9% of patients with RS-negative disease and 86.0% of those with baseline serum erythropoietin (sEPO) of no more than 200 IU/L achieving RBC-TI for at least 12 weeks. The median peak Hb was 11.3 g/dL, representing a median change from baseline to maximum Hb of 3.2 g/dL. Responses were rapid, with 86.4% of primary endpoint responders achieving TI with onset as early as cycle 1.
In the ESA-R/R/I cohort, RBC-TI of at least 12 weeks was achieved in 50.0% of patients overall, including 36.8% of those with RS-negative disease and 56.5% of those with sEPO of no more than 200 IU/L. The median duration of RBC-TI of at least 12 weeks was 59.6 weeks overall and was not reached for patients with sEPO ≤ 200 IU/L. The median peak Hb was 9.8 g/dL (median change from baseline, +2.4 g/dL), and 68.8% of primary endpoint responders achieved TI with onset as early as cycle 1.
What did the safety analysis show?
Treatment-emergent adverse effects (TEAEs) occurred in 94.4% of ESA-naive and 100% of ESA-R/R/I patients; treatment-related TEAEs were observed in 29.6% and 46.2% of patients, respectively. Grade 3/4 TEAEs occurred in 68.5% of ESA-naive and 53.8% of ESA-R/R/I patients, with treatment-related grade 3/4 TEAEs occurring in 11.1% and 7.7%, respectively. There were no treatment-related grade 5 TEAEs in either cohort. Serious TEAEs were observed in 40.7% and 38.5%, though treatment-related serious TEAEs were rare (1.9% and 0%, respectively).
AEs of interest included asthenia or fatigue (16.7% and 36.5%), fractures (13.0% and 11.5%), and hypertension (11.1% and 13.5%) in the ESA-naive and ESA-R/R/I cohorts, respectively. Treatment discontinuation due to AEs occurred in 9.3% of ESA-naive and 3.8% of ESA-R/R/I patients. No patients in either cohort progressed to acute myeloid leukemia during the treatment period.
References
- Della Porta MG, Diez Campelo M, 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 EHA Congress; June 11-14, 2026; Stockholm, Sweden. Abstract S173.
- US FDA approves Bristol Myers Squibb's Reblozyl (luspatercept-aamt) as first-line treatment of anemia in adults with lower-risk myelodysplastic syndromes who may require transfusions. News release. Bristol Myers Squibb. August 28, 2023. Accessed June 12, 2026. https://news.bms.com/news/details/2023/U.S.-FDA-Approves-Bristol-Myers-Squibbs-Reblozyl-luspatercept-aamt-as-First-Line-Treatment-of-Anemia-in-Adults-with-Lower-Risk-Myelodysplastic-Syndromes-MDS-Who-May-Require-Transfusions/default.aspx
