LUSPATERCEPT INITIATED AT THE MAXIMUM-APPROVED DOSE IN PATIENTS WITH LOWER-RISK MYELODYSPLASTIC SYNDROMES WHO REQUIRE TRANSFUSIONS: PRIMARY ANALYSIS FROM MAXILUS

@article{geraldino2026luspatercept,
  title = {{LUSPATERCEPT INITIATED AT THE MAXIMUM-APPROVED DOSE IN PATIENTS WITH LOWER-RISK MYELODYSPLASTIC SYNDROMES WHO REQUIRE TRANSFUSIONS: PRIMARY ANALYSIS FROM MAXILUS}},
  author = {Thais Herrero GERALDINO and Matteo Giovanni DELLA PORTA and Maria Diaz CAMPELO and Valeria SANTINI and Rena BUCKSTEIN and Lionel ADÈS and Bhavana BHATNAGAR and Yinzhi LAI and Dimana MITEVA and Ali MCBRIDE and Krzysztof MADRY and Luke FLETCHER and Dries DEEREN and Thomas CLUZEAU and David VALCÁRCEL and Jose Miguel TORREGROSA-DIAZ and Sebastian GROSICKI and Eyck VON DER HEYDE and Uwe PLATZBECKER and Sangeetha VENUGOPAL and Amer M ZEIDAN},
  journal = {Hematology, Transfusion and Cell Therapy},
  year = {2026},
  month = oct,
  doi = {10.1016/j.htct.2026.107957},
  url = {https://doi.org/10.1016/j.htct.2026.107957},
  note = {CC BY},
}

TY  - JOUR
TI  - LUSPATERCEPT INITIATED AT THE MAXIMUM-APPROVED DOSE IN PATIENTS WITH LOWER-RISK MYELODYSPLASTIC SYNDROMES WHO REQUIRE TRANSFUSIONS: PRIMARY ANALYSIS FROM MAXILUS
AU  - Thais Herrero GERALDINO
AU  - Matteo Giovanni DELLA PORTA
AU  - Maria Diaz CAMPELO
AU  - Valeria SANTINI
AU  - Rena BUCKSTEIN
AU  - Lionel ADÈS
AU  - Bhavana BHATNAGAR
AU  - Yinzhi LAI
AU  - Dimana MITEVA
AU  - Ali MCBRIDE
AU  - Krzysztof MADRY
AU  - Luke FLETCHER
AU  - Dries DEEREN
AU  - Thomas CLUZEAU
AU  - David VALCÁRCEL
AU  - Jose Miguel TORREGROSA-DIAZ
AU  - Sebastian GROSICKI
AU  - Eyck VON DER HEYDE
AU  - Uwe PLATZBECKER
AU  - Sangeetha VENUGOPAL
AU  - Amer M ZEIDAN
PY  - 2026
DA  - 2026/10/23
JO  - Hematology, Transfusion and Cell Therapy
DO  - 10.1016/j.htct.2026.107957
UR  - https://doi.org/10.1016/j.htct.2026.107957
AB  - Background: MAXILUS is an open-label, global, phase 3b study (NCT06045689) evaluating luspatercept (LUSPA) initiated at the maximum-approved dose (1.75 mg/kg) in patients (pts) with lower-risk myelodysplastic syndromes (LR-MDS) who are erythropoiesis-stimulating agent (ESA)–naive or –relapsed/refractory or intolerant (R/R/I) and require transfusions. Aim: To report safety and efficacy outcomes of LUSPA based on primary analysis of MAXILUS after 24 wks of treatment (tx). Material and Methods: Eligible pts (≥ 18 y; non-del[5q] LR-MDS per IPSS-R; ≥ 1 unit packed red blood cells [RBCs] ≤ 8 wks before tx; ECOG PS ≤ 2) received SC LUSPA 1.75 mg/kg Q3W. Primary endpoint (PE) was RBC-transfusion independence (RBC-TI) ≥ 8 wks with concurrent mean Hb increase ≥ 1 g/dL (Wks 1–24). Secondary endpoints included RBC-TI ≥ 8 and ≥ 12 wks (Wks 1–24), modified erythroid hematologic improvement (mHI-E; Wks 1–24), and safety. Efficacy by subgroups was assessed. Results: At cutoff (Oct 1, 2025), 106 pts (ESA-naive, n = 54; ESA-R/R/I, n = 52) received ≥ 1 LUSPA dose; median age was 76.0 y in both cohorts. Median (IQR) time since diagnosis was 2.2 (0.3–9.2) and 25.2 (10.0–65.5) mos in the ESA-naive and ESA-R/R/I cohorts, respectively. Median (IQR) follow-up was 11.1 (7.7–13.7) and 11.7 (9.2–14.3) mos; 51.9% and 57.7% had an SF3B1 mutation; 42.6% and 36.5% had ring sideroblast–negative (RS–) status; and 77.8% and 44.2% had baseline (BL) serum erythropoietin (sEPO) ≤ 200 IU/L, respectively. ESA-naive pts: PE was achieved in 81.5% of pts; RBC-TI ≥ 8 wks in 83.3% and ≥ 12 wks in 75.9%. RBC-TI ≥ 12 wks was achieved in 73.9% of RS– pts and 86.0% of BL sEPO ≤ 200 IU/L pts. mHI-E was achieved in 87.0% of pts. At cutoff, 70.4% of pts remained on tx, 1.9% completed, and 27.8% discontinued (11.1% from lack of efficacy). Median tx duration was 47.3 (range, 10.7–71.1) wks; 24.1% of pts had ≥ 1 dose reduction; 51.9% had ≥ 1 dose delay. Any grade tx-emergent adverse events (TEAEs) occurred in 94.4% of pts (29.6% tx-related); 20.4% led to tx interruption; grade 3/4 TEAEs occurred in 68.5% (11.1% tx-related). HR-MDS progression occurred in 3.7% of pts; none progressed to AML. ESA-R/R/I pts: PE was achieved in 61.5% of pts; RBC-TI ≥ 8 wks in 67.3% and ≥ 12 wks in 50.0%. RBC-TI ≥12 wks was achieved in 36.8% of RS– pts and 56.5% of BL sEPO ≤ 200 IU/L pts. mHI-E was achieved in 76.9% of pts. At cutoff, 38.5% of pts remained on tx, 1.9% completed, and 59.6% discontinued (23.1% from lack of efficacy). Median tx duration was 43.4 (range, 2.1–97.1) wks; 9.6% of pts had ≥ 1 dose reduction; 42.3% had ≥ 1 dose delay. Any grade TEAEs occurred in 100% of pts (46.2% tx-related); 21.2% led to tx interruption; grade 3/4 TEAEs occurred in 53.8% (7.7% tx-related). HR-MDS progression occurred in 3.8% of pts; none progressed to AML. Discussion and Conclusions: With 11 mos follow-up, LUSPA initiated at 1.75 mg/kg led to high, sustained PE achievement in both cohorts. Sustained RBC-TI ≥12 wks occurred in pts with RS– status and low BL sEPO. RBC-TI and mHI-E were notable in both cohorts. LUSPA was well tolerated; few pts progressed to HR-MDS, in line with known rates, and none to AML. The MAXILUS primary analysis reinforces the favorable safety and efficacy profile of LUSPA at the maximum-approved dose in LR MDS.
SN  - 2531-1379
SN  - 2531-1387
ER  -