Real-world (RW) outcomes of patients (pts) with lower-risk myelodysplastic syndrome (LR-MDS) receiving first-line (1L) luspatercept (LUSPA) or 1L erythropoiesis-stimulating agents (ESA) in the US.

6570 Background: LR-MDS pts receiving ESAs for anemia often experience treatment (tx) resistance or relapse. Evidence from the COMMANDS trial led to LUSPA’s US FDA approval in August 2023 as 1L tx for anemia in pts with LR-MDS. This is the first study assessing RW characteristics and outcomes in pts with LR-MDS receiving 1L LUSPA or ESA after 1L LUSPA approval. Methods: Interim data from an ongoing, retrospective medical records review of pts with LR-MDS receiving 1L LUSPA or ESA was collected (17 Oct 2024-19 Dec 2024; target sample size = 200 pts per cohort). Eligible adult pts had IPSS/IPSS-R-defined diagnosis of LR-MDS and initiated 1L LUSPA or ESA between 28 Aug 2023-31 Jul 2024 (tx initiation date = index date). Outcomes were descriptively analyzed; pt characteristics and changes in hemoglobin (Hb) and red blood cell (RBC) transfusion requirements during the first 6 months (mos) of 1L anemia tx are reported. Results: 103 pts (1L LUSPA: 46; 1L ESA: 57) were included in the interim data.In the LUSPA and ESA cohorts, respectively,median age at index was 67.7 and 62.9 yrs; 63.0% and 66.7% were White; 54.3% and 40.4% were female; 28.3% and 10.5% had SF3B1 mutation; 93.5% and 68.4% had ECOG 0/1; and median follow-up was 7.9 and 8.4 mos. IPSS/IPSS-R risk status was intermediate-1/intermediate for 21.7% of LUSPA pts and 8.8% of ESA pts. Of pts with known ring sideroblast (RS) level, 62.2% (23/37) of LUSPA pts and 71.8% (28/39) of ESA pts were RS negative. Baseline (BL) sEPO was <200 IU/L for 30.6% (11/36) of LUSPA pts and 78.9% (30/38) of ESA pts. Most ptsreceiving 1L LUSPA achieved Hb increase of ≥1.5 g/dL (LUSPA: 89.1%; ESA: 56.1%) in the first 6 mos of tx. Of pts who were RBC transfusion-dependent (RBC-TD) at BL, a greater proportion of LUSPA pts became RBC transfusion-independent (RBC-TI) vs ESA pts (91.7% vs 71.4%) in the first 3 mos (Table). Updated results for the full cohort to be presented at the meeting. Conclusions: During the first 6 mos of tx,a higher proportion of ptsreceiving 1L LUSPA showed improvement in Hb and a reduced need for RBC compared to those receiving 1L ESA. This analysis corroborates the results of the COMMANDS trial and demonstrates the favorable RW effectiveness of 1L LUSPA vs 1L ESA for anemia treatment in LR-MDS. 1L LUSPA (n=46) 1L ESA (n=57) Mean (SD) BL Hb, a g/dL 7.7 (0.9) 8.2 (1.2) Pts with Hb increase by ≥1.5 g/dL after tx, n (%) 41 (89.1) 32 (56.1) Pts with Hb increase by ≥1.5 g/dL for ≥8 wks, n (%) 37 (80.4) 27 (47.4) Mean (SD) Hb change from BL during first 6 mos of tx, g/dL 1.7 (1.0) 1.0 (1.0) BL RBC-TD pts with follow-up RBC data known, n 12 14 Became RBC-TI (0 transfusions for ≥8 wks) within first 3 mos of tx, n (%) 11 (91.7) 10 (71.4) Median time to RBC-TI, mos 0.8 1.9 RBC-TI for ≥12 wks, n (%) 11 (91.7) 9 (64.3) Decreased RBC need by ≥50% in first 16 wks of tx among pts with ≥1 BL transfusion, n (%) 9 (75.0) 6 (42.9) a Evaluable pts (LUSPA, n=42; ESA, n=53).