Long-term utilization and benefit of luspatercept in patients (pts) with lower-risk myelodysplastic syndromes (LR-MDS) from the MEDALIST trial.

7056 Background: Luspatercept was previously shown to improve anemia in the phase 3 MEDALIST trial of pts with LR-MDS ineligible, intolerant, or refractory to erythropoiesis-stimulating agents (ESAs). Here, we report the long-term clinical value of luspatercept treatment (Tx) in pts from the MEDALIST study including dosing and rates of progression to acute myeloid leukemia (AML) and high-risk MDS (HR-MDS). Methods: Eligible pts were ≥ 18 y of age, had LR-MDS requiring regular red blood cell (RBC) transfusions, and were ineligible/intolerant or refractory to ESAs. Pts were randomized 2:1 to subcutaneous luspatercept or placebo every 3 wk for 24 wk. The primary endpoint was RBC transfusion independence (RBC-TI) ≥ 8 wk during wk 1–24. MEDALIST pts were eligible for enrollment into the long-term follow-up study. Median duration of Tx and cumulative duration of response were determined by Kaplan–Meier (KM) analysis. Total person-years for pts at risk of HR-MDS/AML progression was calculated from LR-MDS diagnosis to HR-MDS/AML diagnosis, or to last HR-MDS/AML follow-up date for pts who did not progress. Results: As of January 15, 2021, the median duration of Tx was 11.70 (95% CI, 8.97–16.33) mo for luspatercept pts and 5.52 (95% CI, 5.52–5.59) mo for placebo pts. Of those enrolled in MEDALIST, 106/153 (69.3%) pts receiving luspatercept and 64/76 (84.2%) receiving placebo escalated to the maximum dose of 1.75 mg/kg. During the entire Tx phase, RBC-TI ≥ 8 wk was observed in 74/153 (48.4%) and 12/76 (15.8%) pts in the luspatercept and placebo arms, respectively, with a median cumulative duration of response of 80.7 (95% CI, 53.71–154.14) wk and 21.0 (95% CI, 10.86–NE) wk, respectively. During the entire Tx period, RBC-TI ≥ 16 wk was observed in 48/153 (31.4%) and 6/76 (7.9%) pts in the luspatercept and placebo arms, respectively (Table). Among pts randomized to luspatercept, 13/153 (8.5%) progressed to HR-MDS/AML during the entire Tx period, compared with 5/76 (6.6%) for placebo. The total person-years for pts randomized to luspatercept at risk of progressing to HR-MDS/AML was 401.7 y vs 190.9 y for placebo. Conclusions: Pts receiving luspatercept had an extended period of clinical benefit and > 50% of pts continued to receive luspatercept for > 1 y, the majority of whom underwent dose escalations to achieve an optimal response. Pts experienced durable responses with luspatercept, with a median cumulative duration of RBC-TI response of approximately 20 mo. Pts receiving luspatercept also appeared to have a longer time to HR-MDS/AML progression than those receiving placebo.[Table: see text]