Venetoclax Boosts Remission in High-Risk Myelodysplastic Syndrome
Publication Title: Outcomes of patients with higher-risk myelodysplastic syndromes/neoplasms treated with hypomethylating agents + venetoclax—an analysis from the International Consortium for MDS (icMDS) VALIDATE database
Summary
- Question
- This study examined whether adding venetoclax, a drug that helps cancer cells self-destruct, to hypomethylating agents (HMA), which are standard treatments for higher-risk myelodysplastic syndromes (HR-MDS), improves outcomes. The researchers focused on survival rates, remission rates, and potential benefits for specific patient subgroups.
- Why it Matters
- HR-MDS is a severe blood disorder where bone marrow fails to produce healthy blood cells, often progressing to leukemia. Current treatments like HMA have limited effectiveness, with low remission rates and a median survival of less than two years. Understanding whether combining HMA with venetoclax can improve outcomes is vital for advancing care and potentially offering better options for patients facing this life-threatening condition.
- Methods
- The researchers analyzed data from 1,907 HR-MDS patients treated at 31 centers across nine countries. Patients received either HMA alone (1,773 patients) or HMA with venetoclax (134 patients). Treatment responses and survival outcomes were evaluated using standardized criteria, and subgroups were analyzed based on genetic mutations and disease severity.
- Key Findings
- Adding venetoclax to HMA improved composite remission rates (48.8% versus 27.7% with HMA alone) but did not significantly increase complete remission rates or overall survival. Patients with TP53 wild-type disease (normal functioning of a gene linked to tumor suppression) and those with 10% to 19% bone marrow blasts showed trends toward improved survival with the combination therapy. Additionally, patients treated with HMA/venetoclax were more likely to proceed to stem cell transplantation.
- Implications
- The findings suggest that while venetoclax enhances remission rates, its impact on overall survival is limited to specific patient groups, such as those with TP53 wild-type disease or higher blast percentages. This highlights the need for personalized treatment approaches in HR-MDS. The increased likelihood of stem cell transplantation with HMA/venetoclax also underscores its potential role in preparing patients for curative procedures.
- Next Steps
- Further research is needed to confirm the benefits of venetoclax for specific HR-MDS subgroups and explore its use in combination therapies. Randomized trials focusing on patients with TP53 wild-type disease or high blast counts could provide more definitive insights into its effectiveness.
- Funding Information
- This research was supported by a grant from the Edward P. Evans Foundation. Additional funding was provided by the German Cancer Aid through a Mildred-Scheel scholarship (grant no.: 70114570), Associazione Italiana per la Ricerca sul Cancro (AIRC) IG-26537-2021, the European Union Horizon 2020/2023 program and Innovative Health initiative (grants GenoMed4All #101017549, Synthema #1101095530, Synthia #101172872, RealiseD #101165912), and AIRC grants #29483 and #21267. Support was also received from the Japan Society for the Promotion of Science (JSPS) under the Grant-in-Aid for Specially Promoted Research (24H00009). The content is solely the responsibility of the authors and does not necessarily represent the official views of the grantors. Yale University also provided funding and support for this research.
Full Citation
Bewersdorf JP, Kewan T, Lanino L, Wei W, Rudra Gupta T, Stempel JM, Al Ali NH, DeZern AE, Sekeres MA, Uy GL, Urrutia S, Carraway HE, Desai P, Griffiths EA, Stein EM, Brunner AM, McMahon C, Shallis RM, Zeidner JF, Savona MR, Hawkins H, Chandhok NS, Logothetis CN, Bidikian A, Getz TM, Roboz GJ, Rolles B, Wang ES, Harris AC, Amaya ML, Ball S, Grenet J, Xie Z, Madanat YF, Abaza Y, Badar T, Campos J, Haferlach T, Maciejewski JP, Sallman D, Enjeti A, Al-Rabi K, Halahleh K, Hiwase D, Diez-Campelo M, Valcarcel D, Haferlach C, Pleyer L, Kotsianidis I, Pappa V, Santini V, Consagra A, Al-Kali A, Ogawa S, Nannya Y, Stahl M, Della Porta MG, Komrokji RS, Zeidan AM. Outcomes of patients with higher-risk myelodysplastic syndromes/neoplasms treated with hypomethylating agents + venetoclax—an analysis from the International Consortium for MDS (icMDS) VALIDATE database. Blood Cancer Journal 2026 DOI: 10.1038/s41408-026-01543-6.
This AI-assisted summary has been reviewed and approved by at least one of the study's authors to ensure it accurately reflects the research.
Authors
Jan Philipp Bewersdorf, MD, FACP
First AuthorAssistant Professor
Amer Zeidan, MBBS, MD
Last AuthorProfessor of Internal Medicine (Hematology)