Hypomethylating agents plus venetoclax for high-risk MDS and CMML as bridge therapy to transplant: a GESMD study

• DOI: 10.1186/s40164-025-00652-5
• Publication Date: 2025-04-26T05:32:45Z
• Authors: Ines Zugasti; Monica Lopez-Guerra; Sandra Castaño-Díez; Daniel Esteban; Alejandro Avendaño; Helena Pomares; Ana Perez; Sara García-Ávila; Irene Padilla Conejo; Cristina de la Fu...; Alexandra Martíne...; Beatriz Merchán; Carlos Jiménez-Vi...; Francesca Guijarro; Jose Ramón Álamo; Albert Cortes-Bul...; Victor Torrecillas; Lucia Mont; Esther Carcelero; Gisela Riu; Lurdes Zamora; Joan Bargay; Ana Triguero; Maria Suarez-Lledó; Maria Queralt Salas; Felix López-Cadenas; Fernando Ramos; Blanca Xicoy; David Valcárcel; Montserrat Arnan; Carmen Martínez; Montserrat Rovira; Francesc Fernánde...; Maria Díez-Campelo; Jordi Esteve; Marina Díaz-Beyá

Abstract

Background High-risk myelodysplastic syndromes (HR-MDS) and chronic myelomonocytic leukemia (CMML) remain therapeutic challenges with suboptimal outcomes. The only potentially curative treatment is allogeneic stem cell transplantation (allo-SCT). The most frequent pre-allo-SCT treatment is monotherapy with hypomethylating agents (HMA), but approximately 40% of patients cannot proceed to allo-SCT, mainly due to disease progression. Recent evidence suggests that combining HMA with venetoclax (HMA/VEN) could increase HMA efficacy in HR-MDS but it remains unclear if this combination could bridge more patients to allo-SCT.

Methods We retrospectively evaluated HMA/VEN as a bridge to allo-SCT in 30 patients with HR-MDS or CMML eligible for transplant. Eighteen patients were treatment-naïve and 12 were refractory or relapsed (R/R).

Results As defined by the IWG 2023 criteria, the overall response rate (ORR) was 90% and the composite complete response rate was 77%. For the R/R patients, ORR was 83%. The allo-SCT rate was 83%, and the allo-SCT rate of those patients treated exclusively with HMA/VEN without further bridge therapies was 76%. One- and two-year post-allo-SCT survival was 75% and two-year cumulative incidence of relapse was 30.5%. Follow-up of measurable residual disease identified some molecular relapses that were controlled with preemptive treatment.

Conclusions Our findings indicate that HMA/VEN combination therapy shows promise as a bridging strategy to allo-SCT in HR-MDS and CMML.