Hypomethylating agents plus venetoclax for high-risk MDS and CMML as bridge therapy to transplant: a GESMD study
Inés Zugasti, Mònica López‐Guerra, Sandra Castaño‐Díez, Daniel Esteban, Alejandro Avendaño, Helena Pomares, Ana Pérez, Sara García-Ávila, Irene Conejo, Cristina de la Fuente Montes, Alexandra Martínez‐Roca, Beatriz Merchán, Carlos Jiménez‐Vicente, Francesca Guijarro, José Álamo, Albert Cortés‐Bullich, Víctor Torrecillas, Lucie Salomon du Mont, Esther Carcelero, Gisela Riu-Viladoms, Lurdes Zamora, Joan Bargay, Ana Triguero, María Suárez‐Lledó, María Queralt Salas, Félix López Cadenas, Fernando Ramos, Blanca Xicoy, David Valcárcel, Montserrat Arnán, Carmen Martı́nez, Montserrat Rovira, Francesc Fernández‐Avilés, María 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.