Luspatercept Demonstrates Durable Transfusion Independence in Lower-Risk MDS Across Two Pivotal Trials
核心洞察
In the phase 3b MAXILUS trial, 81.5% of ESA-naive patients with lower-risk MDS achieved RBC transfusion independence for ≥8 weeks plus concurrent Hb increase ≥1 g/dL.
Long-term COMMANDS data show luspatercept nearly doubled the duration of transfusion independence compared with epoetin alfa, with some "super-responders" remaining transfusion-free for ≥2.5 years.
MAXILUS results affirm the importance of early treatment initiation with luspatercept at the maximum approved dose in both ESA-naive and ESA-relapsed/refractory populations.
Luspatercept-aamt (Reblozyl) continues to solidify its position as a cornerstone of frontline therapy for lower-risk myelodysplastic syndromes (搜索) (LR-MDS), with new data from the phase 3b MAXILUS trial and extended follow-up from the phase 3 COMMANDS trial demonstrating durable transfusion independence across diverse patient subgroups.
Findings presented at the 2026 European Hematology Association (EHA) Congress showed that among ESA-naive patients in MAXILUS, 81.5% achieved red blood cell transfusion independence (RBC-TI) for at least 8 weeks plus a concurrent hemoglobin (Hb) increase of at least 1 g/dL. In the relapsed/refractory cohort, 61.5% met this same endpoint.
" 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," said study investigator Matteo Giovanni Della Porta, of Cancer Center IRCCS Humanitas Research Hospital and Humanitas University in Milan, Italy.
MAXILUS Trial Design and Key Outcomes
The open-label phase 3b MAXILUS trial (NCT06045689) enrolled patients with ESA-naive or ESA-relapsed/refractory/intolerant MDS. Participants received luspatercept at 1.75 mg/kg subcutaneously every 3 weeks. After a 24-week response evaluation, patients without clinical benefit or with progression per International Working Group (IWG) criteria discontinued therapy, while responders could continue treatment for up to 2 years.
In the ESA-naive cohort (n = 54), 83.3% achieved RBC-TI for at least 8 weeks, 75.9% attained RBC-TI for at least 12 weeks, and 72.2% reached RBC-TI for at least 12 weeks plus a concurrent Hb increase of at least 1.5 g/dL. Modified erythroid hematologic improvement (mHI-E) was observed in 87.0% of patients.
Subgroup analysis within the ESA-naive arm revealed that 73.9% of RS-negative patients, 77.4% of RS-positive patients, 86.0% of those with serum erythropoietin (sEPO) below 200 IU/L, and 36.4% of those with sEPO above 200 IU/L achieved RBC-TI for at least 12 weeks. The median peak Hb was 11.3 g/dL (IQR, 9.9-12.4) within 24 weeks, with a median change from baseline to maximum Hb of 3.2 g/dL (IQR, 2.5-4.1).
Among patients with relapsed/refractory disease following prior ESAs (n = 52), 67.3% had RBC-TI for at least 8 weeks, 50.0% for at least 12 weeks, and 40.4% for at least 12 weeks with concurrent Hb increase of at least 1.5 g/dL. The mHI-E rate was 76.9%. The median peak Hb reached 9.8 g/dL (IQR, 8.9-10.7), with a median Hb change of 2.4 g/dL (IQR, 1.6-3.5).
Safety Profile
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. Grade 3/4 events were reported in 68.5% versus 53.8% of patients, respectively. Four patients in the relapsed/refractory group experienced grade 5 TEAEs. Treatment-emergent events of interest included asthenia (16.7% vs 36.5%), fractures (13.0% vs 11.5%), and hypertension (11.1% vs 13.5%).
At the time of analysis, 70.4% of ESA-naive and 38.5% of relapsed/refractory patients remained on therapy. Dose delays due to predose Hb of 12 g/dL or higher occurred in 33.3% and 3.8%, while dose reductions due to Hb increases of at least 2 g/dL were required in 18.5% and 3.8%, respectively.
COMMANDS Long-Term Data Reinforce Frontline Role
Extended follow-up from the phase 3 COMMANDS trial (NCT03682536), which compared luspatercept with epoetin alfa in ESA-naive, transfusion-dependent patients, has further cemented the drug's frontline role. The 3-year data showed luspatercept nearly doubled the duration of transfusion independence compared with epoetin alfa.
"COMMANDS changed the treatment landscape for our [patients with] lower-risk MDS," said Raji Shameem, MD, hematologist and medical oncologist at Orlando Health Cancer Institute. "It has raised the bar for what we expect from frontline therapy in low-risk MDS. Seeing patients achieve a year and a half or longer without a transfusion is remarkable, and I feel that's the goal."
Amer Zeidan, MBBS, MD, professor of medicine at Yale School of Medicine and chief of the Division of Hematologic Malignancies, highlighted the emergence of "super-responders"—patients achieving the longest transfusion independence of 2.5 years or more. "With each additional piece of data, the role of luspatercept in frontline treatment is being cemented. We saw trends toward improved survival, we see higher response rates in most patients, and we see longer duration of response," Zeidan said.
The median time since original MDS diagnosis in MAXILUS was 2.2 months for the ESA-naive group versus 25.2 months for the relapsed/refractory group, underscoring the potential benefit of early intervention. Both trials enrolled patients with RS-positive and RS-negative status, supporting luspatercept's broad applicability across the LR-MDS population.