Hypomethylating agents plus venetoclax for high-risk MDS and CMML as bridge therapy to transplant: a GESMD study
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...
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BMC
2025-04-01
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| Series: | Experimental Hematology & Oncology |
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| Online Access: | https://doi.org/10.1186/s40164-025-00652-5 |
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| author | 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 Fuente Montes Alexandra Martínez-Roca Beatriz Merchán Carlos Jiménez-Vicente Francesca Guijarro Jose Ramón Álamo Albert Cortes-Bullich 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 Fernández-Avilés Maria Díez-Campelo Jordi Esteve Marina Díaz-Beyá |
| author_facet | 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 Fuente Montes Alexandra Martínez-Roca Beatriz Merchán Carlos Jiménez-Vicente Francesca Guijarro Jose Ramón Álamo Albert Cortes-Bullich 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 Fernández-Avilés Maria Díez-Campelo Jordi Esteve Marina Díaz-Beyá |
| author_sort | Ines Zugasti |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-13fddf8f6f134dacbb9a3201bb4d35b3 |
| institution | OA Journals |
| issn | 2162-3619 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Experimental Hematology & Oncology |
| spelling | doaj-art-13fddf8f6f134dacbb9a3201bb4d35b32025-08-20T02:30:22ZengBMCExperimental Hematology & Oncology2162-36192025-04-0114111510.1186/s40164-025-00652-5Hypomethylating agents plus venetoclax for high-risk MDS and CMML as bridge therapy to transplant: a GESMD studyInes Zugasti0Monica Lopez-Guerra1Sandra Castaño-Díez2Daniel Esteban3Alejandro Avendaño4Helena Pomares5Ana Perez6Sara García-Ávila7Irene Padilla Conejo8Cristina de la Fuente Montes9Alexandra Martínez-Roca10Beatriz Merchán11Carlos Jiménez-Vicente12Francesca Guijarro13Jose Ramón Álamo14Albert Cortes-Bullich15Victor Torrecillas16Lucia Mont17Esther Carcelero18Gisela Riu19Lurdes Zamora20Joan Bargay21Ana Triguero22Maria Suarez-Lledó23Maria Queralt Salas24Felix López-Cadenas25Fernando Ramos26Blanca Xicoy27David Valcárcel28Montserrat Arnan29Carmen Martínez30Montserrat Rovira31Francesc Fernández-Avilés32Maria Díez-Campelo33Jordi Esteve34Marina Díaz-Beyá35Hospital Clínic BarcelonaHospital Clínic BarcelonaHospital Clínic BarcelonaHospital Clínic BarcelonaHospital Universitario de SalamancaInstitut Català d’Oncologia, Hospital Duran I ReynalsHospital Universitario Vall d´HebrónHospital del MarHospital Universitario de LeónInstitut Català d’Oncologia (ICO), Hospital Germans Trias I PujolHospital Clínic BarcelonaHospital Clínic BarcelonaHospital Clínic BarcelonaHospital Clínic BarcelonaHospital Clínic BarcelonaHospital Clínic BarcelonaUniversitat de BarcelonaUniversitat de BarcelonaHospital Clínic BarcelonaHospital Clínic BarcelonaInstitut Català d’Oncologia (ICO), Hospital Germans Trias I PujolHospital Son LlátzerHospital Clínic BarcelonaHospital Clínic BarcelonaHospital Clínic BarcelonaHospital del MarHospital Universitario de LeónInstitut Català d’Oncologia (ICO), Hospital Germans Trias I PujolHospital Universitario Vall d´HebrónInstitut Català d’Oncologia, Hospital Duran I ReynalsHospital Clínic BarcelonaHospital Clínic BarcelonaHospital Clínic BarcelonaHospital Universitario de SalamancaHospital Clínic BarcelonaHospital Clínic BarcelonaAbstract 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.https://doi.org/10.1186/s40164-025-00652-5MDSCMMLMDS/MPNAllo-SCTBridge therapyCytoreductive therapy |
| spellingShingle | 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 Fuente Montes Alexandra Martínez-Roca Beatriz Merchán Carlos Jiménez-Vicente Francesca Guijarro Jose Ramón Álamo Albert Cortes-Bullich 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 Fernández-Avilés Maria Díez-Campelo Jordi Esteve Marina Díaz-Beyá Hypomethylating agents plus venetoclax for high-risk MDS and CMML as bridge therapy to transplant: a GESMD study Experimental Hematology & Oncology MDS CMML MDS/MPN Allo-SCT Bridge therapy Cytoreductive therapy |
| title | Hypomethylating agents plus venetoclax for high-risk MDS and CMML as bridge therapy to transplant: a GESMD study |
| title_full | Hypomethylating agents plus venetoclax for high-risk MDS and CMML as bridge therapy to transplant: a GESMD study |
| title_fullStr | Hypomethylating agents plus venetoclax for high-risk MDS and CMML as bridge therapy to transplant: a GESMD study |
| title_full_unstemmed | Hypomethylating agents plus venetoclax for high-risk MDS and CMML as bridge therapy to transplant: a GESMD study |
| title_short | Hypomethylating agents plus venetoclax for high-risk MDS and CMML as bridge therapy to transplant: a GESMD study |
| title_sort | hypomethylating agents plus venetoclax for high risk mds and cmml as bridge therapy to transplant a gesmd study |
| topic | MDS CMML MDS/MPN Allo-SCT Bridge therapy Cytoreductive therapy |
| url | https://doi.org/10.1186/s40164-025-00652-5 |
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