MDS-128: Azacitidine and Venetoclax Combination for Upfront Treatment of Higher-Risk Myelodysplastic Syndromes

Abstract

<h3>Context:</h3> Azacitidine (aza) remains the backbone of treating higher-risk MDS patients (pts), with less than 20% of pts achieving complete response (CR) and median overall survival of 14–18 months. Ongoing studies in higher-risk MDS are assessing the role of adding venetoclax (ven) to aza in higher-risk MDS. <h3>Objective:</h3> We report, here, single-institution experience of aza/ven combination in the upfront treatment of higher-risk MDS, comparing it to historical aza alone. <h3>Design:</h3> We identified 35 pts who received aza/ven for intermediate or higher-risk MDS by R-IPSS compared to 1175 similar-risk MDS pts who historically received aza upfront therapy alone. <h3>Results:</h3> The median follow-up for the aza/ven group was 15 months (mo) compared to 93 mo for aza alone. No differences were observed in baseline demographic or disease characteristics comparing aza/ven group to aza alone except for higher rates of ASXL-1 and N-RAS somatic mutations (SM) among aza/ven treated pts. There was no difference in median OS among the two groups: median OS was 20 mo for both groups. The CR/marrow CR (mCR) rate was higher with the aza/ven combination, 71% (31%/40%), compared to 25% for aza alone (13%/12%) (p<.005). Among pts with ASXL-1 SM, the CR rate was 47% compared to 9% for aza alone (p <.005). More pts treated with aza/ven proceeded to allogeneic hematopoietic stem cell transplant (AHSCT) (40% <i>vs</i> 23%, p=.04). The median OS for pts treated with aza/ven followed by AHSCT was not reached compared to 31 mo for aza alone followed by AHSCT (p=.17). The 2-year survival rate for pts who underwent AHSCT was 90% for aza/ven compared to 51% for the aza alone group. <h3>Conclusion:</h3> Aza/ven combination is associated with higher responses overall and among ASXL-1 SM higher-risk MDS pts and encouraging early data support aza/ven as a bridge to AHSCT, with 90% 2-year OS.