Response to luspatercept can be predicted and improves overall survival in the real‐life treatment of LR‐MDS

We explored the impact of luspatercept therapy on overall survival (OS) and possible predictors of response in low-risk (LR) myelodysplastic syndrome (MDS) patients. We evaluated 331 anemic patients treated with luspatercept. Hematological response (HI) was defined as (i) hemoglobin (Hb) increase of ≥1.5 g/dL in nontransfusion-dependent (NTD) patients, and (ii) red blood cell (RBC) transfusion independence (TI) with a concomitant Hb increase of ≥1.5 g/dL, or RBC-TI without an Hb increase of 1.5 g/dL, or >50% reduction in RBC transfusion burden (TB) for TD patients. Response was observed in 166 patients (50.2%), with significantly higher response in NTD and low TB versus high TB patients (p < 0.001). A significant correlation between lower Molecular International Prognostic Scoring System (IPSS-M) risk scores and response was observed. No statistically significant difference in HI was found in SF3B1-mutated versus wild-type MDS patients (53.8% vs. 40.1%, respectively). SF3B1mut hotspots (K700E vs. others) and variant allele frequencies (VAFs; <38% VAF vs. ≥38% VAF) did not impact on HI. SF3B1-mutated MDS with del5q showed inferior HI compared to other LR-MDS (p = 0.046). The median treatment duration overall was 35 weeks (20.86–90.29), the median time to response was 11 weeks (8.71–21.86), and the median duration of response was 65 weeks (26.5–114). After a median follow-up of 13 months, median OS was not reached (NR) for responders and 24 months for nonresponders (hazard ratio [HR] 0.25, 95% confidence interval 0.14–0.44, p < 0.001). This analysis of 331 luspatercept real-life-treated LR-MDS patients demonstrated a significant OS benefit upon luspatercept response. Low baseline RBC-TB and lower risk IPSS-M scores correlated with higher HI and could constitute predictive markers of response.