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

IF 9.4 1区医学 Q1 HEMATOLOGY

Experimental Hematology & Oncology Pub Date : 2025-04-26 DOI:10.1186/s40164-025-00652-5

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

{"title":"Hypomethylating agents plus venetoclax for high-risk MDS and CMML as bridge therapy to transplant: a GESMD study.","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 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","doi":"10.1186/s40164-025-00652-5","DOIUrl":null,"url":null,"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.","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"14 1","pages":"61"},"PeriodicalIF":9.4000,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12032758/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Experimental Hematology & Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s40164-025-00652-5","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"HEMATOLOGY","Score":null,"Total":0}

引用次数: 0

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.

查看原文本刊更多论文

低甲基化药物加venetoclax作为高危MDS和CMML移植的桥梁治疗：一项GESMD研究。

背景：高风险骨髓增生异常综合征（HR-MDS）和慢性髓单细胞白血病（CMML）仍然是治疗的挑战，结果不理想。唯一可能治愈的治疗方法是同种异体干细胞移植（allo-SCT）。最常见的alloo - sct前治疗是使用低甲基化药物（HMA）的单药治疗，但大约40%的患者不能进行alloo - sct，主要是由于疾病进展。最近的证据表明，HMA联合venetoclax （HMA/VEN）可以提高HMA治疗HR-MDS的疗效，但目前尚不清楚这种联合是否能让更多的患者接受同种细胞移植。方法：我们回顾性评估HMA/VEN作为30例符合移植条件的HR-MDS或CMML患者的同种异体干细胞移植的桥梁。18例患者treatment-naïve， 12例难治性或复发（R/R）。结果：按照IWG 2023标准，总有效率（ORR）为90%，综合完全有效率为77%。对于R/R患者，ORR为83%。同种异体细胞移植率为83%，仅接受HMA/VEN治疗而不接受进一步桥接治疗的患者的同种异体细胞移植率为76%。同种异体移植后1年和2年生存率为75%，2年累计复发率为30.5%。可测量的残余疾病的随访确定了一些分子复发，并通过先发制人的治疗加以控制。结论：我们的研究结果表明，HMA/VEN联合治疗有望作为HR-MDS和CMML中同种异体细胞移植的桥接策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Experimental Hematology & Oncology Medicine-Oncology

CiteScore

12.60

自引率

7.30%

发文量

审稿时长

6 weeks

期刊介绍： Experimental Hematology & Oncology is an open access journal that encompasses all aspects of hematology and oncology with an emphasis on preclinical, basic, patient-oriented and translational research. The journal acts as an international platform for sharing laboratory findings in these areas and makes a deliberate effort to publish clinical trials with 'negative' results and basic science studies with provocative findings. Experimental Hematology & Oncology publishes original work, hypothesis, commentaries and timely reviews. With open access and rapid turnaround time from submission to publication, the journal strives to be a hub for disseminating new knowledge and discussing controversial topics for both basic scientists and busy clinicians in the closely related fields of hematology and oncology.