Outcomes after venetoclax with hypomethylating agents in myelodysplastic syndromes: a systematic review and meta-analysis

Abstract

We present a systematic review and meta-analysis to evaluate outcomes after venetoclax (VEN) with hypomethylating agents (HMA) in myelodysplastic syndromes (MDS). We performed a literature search on PubMed, Cochrane Library, EMBASE, and Clinicaltrials.gov. After screening 2004 manuscripts, 16 studies were included. Data was extracted following PRISMA guidelines. Pooled analysis was done using the meta-package by Schwarzer et al. Proportions with 95% confidence intervals (CI) were computed. We analyzed the outcomes of 373 patients from 11 retrospective studies and five phase 1 b clinical trials. Pooled complete response with or without hematological recovery was 60% (95% CI 0.49–0.7, I²= 67%, n = 373). Hematopoietic cell transplantation was performed in 32% of patients (95% CI 0.2–0.46, I²= 62%, n = 187). Overall mortality was 45% (95% CI 0.31–0.59, I²=54%, n = 140). VEN-HMA combination therapy demonstrated promising outcomes in MDS. Prospective randomized data is needed to ascertain the benefit of VEN and its impact in MDS patients.

Keywords:

• Myelodysplastic syndrome
• venetoclax
• outcomes
• toxicity
• apoptosis

Author contributions

All authors contributed to the manuscript and fulfilled criteria per the uniform requirements set forth by the International Committee of Medical Journal Editors (ICJME) guidelines. All authors have reviewed and approved the final version of the manuscript.

Disclosure statement

No relevant conflict of interest. SHA has speaking, consulting and advisory role, and research funding from in Incyte and Therakos. JPM has speaking, consulting and advisory role in Kite, Juno Therapeutics, Allovir, Magenta Therapeutics, EcoR1 Capital, and has research funding from Novartis, Fresenius Biotech, Astellas Pharma, Bellicum Pharmaceuticals, Gamida Cell, Pluristem Therapeutics, Kite and AlloVir.