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 (<i>p</i> < 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 <i>SF3B1-</i>mutated versus wild-type MDS patients (53.8% vs. 40.1%, respectively). <i>SF3B1</i>mut hotspots (K700E vs. others) and variant allele frequencies (VAFs; <38% VAF vs. ≥38% VAF) did not impact on HI. <i>SF3B1-</i>mutated MDS with del5q showed inferior HI compared to other LR-MDS (<i>p</i> = 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, <i>p </i>< 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.

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Publication Details

Journal
HemaSphere
Published
2025-02-01
DOI
https://doi.org/10.1002/hem3.70086
Citations
10
Primary Topic
Acute Myeloid Leukemia Research
Type
article
Field-Weighted Citation Impact
17.70

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article

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

Sven De Pourcq, Michele Tanturli, Rami S. Komrokji, Giorgio Mattiuz et al.
10 citations
HemaSphere
Acute Myeloid Leukemia Research
17.70
article

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

Sven De Pourcq, Michele Tanturli, Rami S. Komrokji, Giorgio Mattiuz, Alessandro Sanna, Alessia Campagna, Luis E. Aguirre, Angela Consagra, Francesco Restuccia, Jeffrey E. Lancet, Eric Padron, Cristina Amato, Andrew Tucker Kuykendall, Zhuoer Xie, Alessandra Perego, Marco Gabriele Raddi, Onyee Chan, Bruno Fattizzo, Luca Rigodanza, Marta Ubezio, Elena Tofacchi, Giulia Maggioni, Alison Walker, Luca Lanino, Matteo Giovanni Della Porta, Valeria Santini, Gloria Andreossi, Najla H. Al Ali, Marta Riva, David A Sallman
article en
10 citations

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 (<i>p</i> < 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 <i>SF3B1-</i>mutated versus wild-type MDS patients (53.8% vs. 40.1%, respectively). <i>SF3B1</i>mut hotspots (K700E vs. others) and variant allele frequencies (VAFs; <38% VAF vs. ≥38% VAF) did not impact on HI. <i>SF3B1-</i>mutated MDS with del5q showed inferior HI compared to other LR-MDS (<i>p</i> = 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, <i>p </i>< 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.

HemaSphereVol. 9(2)
University of Siena (IT), Humanitas University (IT), Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (IT), Moffitt Cancer Center (US), Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda (IT), Azienda Ospedaliera San Gerardo (IT), Dana-Farber Cancer Institute (US), Azienda USL di Pescara (IT), IRCCS Humanitas Research Hospital (IT), University of Florence (IT)
Associazione Italiana per la Ricerca sul Cancro
Responsible consumption and production
Openalex Percentile: Top 1%
Acute Myeloid Leukemia Research
17.70
DOIOpen Access PDFOpenAlex
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