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

Abstract

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.