Outcomes with venetoclax in myelodysplastic syndromes: A systematic review.

Abstract

e19035 Background: Myelodysplastic syndromes (MDS) are clonal hemopoietic disorders causing cytopenia(s) and increased risk of transformation to acute myeloid leukemia (AML). Venetoclax is a B-cell lymphoma-2 (BCL-2) inhibitor that induces apoptosis in malignant cells. The FDA has approved venetoclax for the treatment of newly diagnosed adult AML patients unfit for intensive chemotherapy and its utility in MDS is being explored. We present a systematic review aimed to evaluate outcomes with venetoclax in MDS patients. Methods: We performed a literature search on 3 databases (Pubmed, Cochrane, and Clinicaltrials.gov) following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. We screened 62 studies using the Mesh terms ‘myelodysplastic syndrome’ and ‘venetoclax’. After excluding review, duplicate and non-relevant articles, 8 studies were included in the analysis. Quality evaluation was done using the NIH quality assessment tool. Pooled analysis was done using the ‘meta’ package (Schwarzer et al, R programming language) and proportions with 95% confidence intervals (CI) were computed. The Inter-study heterogeneity among the studies was assessed using the Q statistic proposed by Cochrane and the I2 index introduced by Higgins and Thompson. Results: We identified 313 patients from 8 studies (1 prospective, 3 retrospective, 2 ex-vivo, 2 clinical trials). Venetoclax was used in combination with hypomethylating agents (HMA) in 6 studies and with other agents in 2 studies. Most patients were pre-treated. Complete response (CR) with or without hematological recovery (CRi) was reported in 45% of patients (95% CI 0.26-0.66, I2= 90%, n = 292). Stable disease (SD) was seen in 18% patients (95% CI 0.08-0.37, I2= 85%, n = 223). Overall response rate (ORR) was 51% (95% CI 0.31-0.70, I2= 89%, n = 122). Hematopoietic stem cell transplant (HCT) was performed in 22% patients (95% CI 0.09-0.44, I2= 75%, n = 122). Twenty percent patients (95% CI 0.15-0.28, I2= 0%, n = 149) died. Common adverse events seen with venetoclax were cytopenias, gastrointestinal side effects and infections, often requiring drug interruption or dose. Conclusions: Despite heterogeneity of available literature, venetoclax seems to be a promising agent in treatment of MDS patients. Prospective clinical trial data is needed to ascertain safety and efficacy of venetoclax in MDS and impact on overall survival, in particular, in patients proceeding to HCT.[Table: see text]