Safety, tolerability, and pharmacokinetics (PK) of luspatercept (LUSPA) at increased injection volumes (up to 2 mL) in patients (pts) with lower-risk myelodysplastic syndromes (LR-MDS) who require red blood cell (RBC) transfusions: Results from MAXILUS.

Abstract

531 Background: LUSPA is approved for anemia in adults with LR-MDS who are erythropoiesis-stimulating agent (ESA)-naive or have had prior ESA failure and require RBC transfusions. At previously FDA-approved 1.2 mL syringe volume cap, LUSPA 1.75 mg/kg dosing requires multiple subcutaneous (SC) injections across anatomical sites (upper arm/thigh/abdomen) that may increase overall treatment (tx) burden. Increasing injection volume up to 2 mL may reduce the number of injections required, optimizing tx delivery and reducing pt burden. The aim of this study is to report exploratory safety, tolerability, PK, and syringe efficiency outcomes with higher-volume LUSPA injections in MAXILUS. Methods: In the phase 3b, open-label, non-randomized MAXILUS trial (NCT06045689), adults with LR-MDS (ESA-naive or with prior ESA failure) initiated SC LUSPA 1.75 mg/kg Q3W. Midway through the ongoing study (May 2024), protocol amendment increased the injection volume from 1.2 to up to 2 mL. Safety, PK, and injection burden were assessed by injection volume category. Results: As of Oct 1, 2025, 106 pts were analyzed; 96 started tx at 1.2 mL injection volume/syringe and 10 at >1.2-≤2 mL/syringe. During tx, 40/96 pts increased from 1.2 to 2 mL injection volume/syringe, resulting in 50 pts receiving up to 2 mL overall. In the 1.2 mL (n=96) vs 2 mL (n=50) groups (not mutually exclusive), 66.7% vs 68% were male, mean age was 75.9 vs 76 y, and total injection number was 2691 vs 623. One immunologic hypersensitivity-type reaction (eyelid edema, not tx-related) was observed in a pt while receiving 1.2 mL injection volume, prior to transitioning up to 2 mL. No pts had immunologic local injection reactions. LUSPA PK was not impacted by injection volume increase, including initiation at 2 mL (Table). Injection number range/cycle was 1-6 in 1.2 mL and 1-4 in 2 mL groups. Pts receiving higher-volume administration (up to 2 mL) required fewer injections per pt, avoiding an estimated total of 358 injections. Conclusions: Higher-volume LUPSA injections were well tolerated, with no new safety signals, and had no impact on PK parameters. Injection volume up to 2 mL reduced injection burden for pts and healthcare professionals, potentially improving pt outcomes. Clinical trial information: NCT06045689 . PK by injection volume. Parameter, mean (SD) ≤1.2 mL at initiation(n=55) a Change to >1.2 mL post-initiation(n=40) >1.2-2 mL at initiation(n=10) Apparent clearance, L/day 0.524 (0.252) 0.505 (0.148) 0.478 (0.0789) Apparent volume of distribution, L 9.09 (2.89) 9.63 (2.55) 8.53 (2.1) Half-life, day 13.1 (3.52) 13.5 (1.97) 12.3 (2.6) Area under concentration-time curve at steady state, day × µg/mL 292 (115) 285 (71.9) 284 (68.4) Max concentration at steady state, µg/mL 17.3 (5.97) 16.8 (3.89) 17.2 (3.56) a One pt was excluded due to missing dose record for PK.