Combination therapy with venetoclax and azacitidine for the treatment of myelodysplastic syndromes with DDX41 mutations

ABSTRACT

Myelodysplastic syndromes (MDS) patients with DEAD-box helicase 41 (DDX41) mutations have been reported to be treated effectively with lenalidomide; however, there are no randomized studies to prove it. Venetoclax and azacitidine are safe and effective in high-risk MDS/AML. In this study, we evaluated the efficacy of venetoclax and azacitidine combination therapy in eight consecutive MDS patients with DDX41 mutations at our centre from March 2021 to November 2023. We retrospectively analyzed the genetic features and clinical characteristics of these patients. Our findings suggest that MDS patients with DDX41 mutation may benefit from the therapy, for six subjects received this regimen as initial therapy and five of the six subjects achieved complete remission.

KEYWORDS:

• Myelodysplastic syndromes
• DDX41
• venetoclax
• azacitidine

Acknowledgement

RPG acknowledges support from the UK National Institute of Health Research (NIHR) Biomedical Research Centre and the Ministry of Science and Technology of China (84000-51200002).

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions

Zhijian Xiao designed the study. Xin Wang acquired the data, analyzed, and interpreted the data, performed statistical analysis; Tiejun Qin, Zefeng Xu, Shiqiang Qu, Bing Li, Lijuan Pan, Qingyan Gao, Meng Jiao participated in clinical information collection. Xin Wang, Robert Peter Gale, and Zhijian Xiao drafted the typescript. All authors approved the typescript, accept responsibility for the content and agreed to submit for publication.

Ethics approval

Ethical approval was approved by the Ethical Committee on Medical Research at Institute of Hematology and Blood Disease Hospital.

Data availability statement

Available from the corresponding authour upon reasonable request and compliant with the laws of China.

Additional information

Funding

This work was supported, in part, by CAMS Initiative Fund for Medical Sciences (Nos. 2022-I2M-1-022 and 2020-I2M-C&T-A-020), Haihe Laboratory of Cell Ecosystem Innovation Fund (22HHXBSS00033), Clinical research fund from National Clinical Research Centre for Blood Diseases (Nos. 2023NCRCA0117 and 2023NCRCA0103) and National Natural Science Funds (Nos. 82170139, 82104785 and 81530008).