Rethinking the feasibility and safety of venetoclax-obinutuzumab in chronic lymphocytic leukemia: non-traditional factors may play a role in clinical practice.

IF 8.2 1区医学 Q1 HEMATOLOGY

Haematologica Pub Date : 2025-06-26 DOI:10.3324/haematol.2025.287799

Anna Maria Frustaci,Andrea Galitzia,Mariano Lucignano,Lorena Appio,Jacopo Olivieri,Alessandro Sanna,Claudia Baraté,Fabrizio Pane,Luana Schiattone,Beatrice Casadei,Isacco Ferrarini,Amalia Figuera,Paolo Sportoletti,Giacomo Loseto,Caterina Stelitano,Andrea Visentin,Melania Celli,Francesca Romana Mauro,Massimiliano Palombi,Marta Coscia,Vanessa Innao,Riccardo Moia,Marina Motta,Filomena Russo,Monica Tani,Annalisa Arcari,Elia Boccellato,Chiara Borella,Enrico Capochiani,Angela Ferrari,Massimo Gentile,Roberta Giachetti,Annamaria Giordano,Martina Bullo,Enrico Lista,Luigi Malandruccolo,Maurizio Musso,Marzia Varettoni,Federico Vozella,Francesca Cibien,Michele Merli,Laura Nocilli,Maria Cristina Pasquini,Azzurra Anna Romeo,Valentina Rossi,Gloria Turri,Anna Vanazzi,Marina Cavaliere,Alessandro Gozzetti,Lara Crucitti,Moira Lucesole,Marina Deodato,Annamaria Tomasso,Arianna Zappaterra,Roberta Murru,Caterina Patti,Luca Laurenti,Alessandra Tedeschi

{"title":"Rethinking the feasibility and safety of venetoclax-obinutuzumab in chronic lymphocytic leukemia: non-traditional factors may play a role in clinical practice.","authors":"Anna Maria Frustaci,Andrea Galitzia,Mariano Lucignano,Lorena Appio,Jacopo Olivieri,Alessandro Sanna,Claudia Baraté,Fabrizio Pane,Luana Schiattone,Beatrice Casadei,Isacco Ferrarini,Amalia Figuera,Paolo Sportoletti,Giacomo Loseto,Caterina Stelitano,Andrea Visentin,Melania Celli,Francesca Romana Mauro,Massimiliano Palombi,Marta Coscia,Vanessa Innao,Riccardo Moia,Marina Motta,Filomena Russo,Monica Tani,Annalisa Arcari,Elia Boccellato,Chiara Borella,Enrico Capochiani,Angela Ferrari,Massimo Gentile,Roberta Giachetti,Annamaria Giordano,Martina Bullo,Enrico Lista,Luigi Malandruccolo,Maurizio Musso,Marzia Varettoni,Federico Vozella,Francesca Cibien,Michele Merli,Laura Nocilli,Maria Cristina Pasquini,Azzurra Anna Romeo,Valentina Rossi,Gloria Turri,Anna Vanazzi,Marina Cavaliere,Alessandro Gozzetti,Lara Crucitti,Moira Lucesole,Marina Deodato,Annamaria Tomasso,Arianna Zappaterra,Roberta Murru,Caterina Patti,Luca Laurenti,Alessandra Tedeschi","doi":"10.3324/haematol.2025.287799","DOIUrl":null,"url":null,"abstract":"The concept of fitness for novel agents in chronic lymphocytic leukemia (CLL) remains debated. Comorbidities and treatment-related logistics are increasingly recognized as key factors in treatment feasibility. Venetoclax-obinutuzumab (VO) has demonstrated efficacy in both fit and unfit patients in clinical trials, yet real-world data remain limited. This retrospective, multicenter study analyzed disease- and patient-related factors affecting VO management and outcomes in 271 patients. Fitness was assessed using comorbidity indices (CLL-CI, CIRS, CCI), ECOG-PS, and caregiver need. Adverse events (AEs) and treatment modifications were evaluated across four treatment phases. Median age was 66 years (19% ≥75); 83% had comorbidities, 34% required polypharmacy, and 10% needed caregiver support. Overall, 96% completed debulking, 89% the full regimen, while 11% discontinued due to toxicity (Tox-DTD). Grade ≥3 AEs occurred in 55%, tumor lysis syndrome in 6%, severe infusion-related reactions in 5%. Overall, 3.3% died during treatment. Unfit patients did not show a significantly higher risk of treatment modifications due to AEs. Dose adjustments were more frequent during debulking. None of the validated fitness scores predicted treatment feasibility or Tox-DTD. Global feasibility was impacted by age (p .002), prior malignancies (p .003), prolonged steroid pre-treatment (p.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"75 1","pages":""},"PeriodicalIF":8.2000,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Haematologica","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3324/haematol.2025.287799","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

The concept of fitness for novel agents in chronic lymphocytic leukemia (CLL) remains debated. Comorbidities and treatment-related logistics are increasingly recognized as key factors in treatment feasibility. Venetoclax-obinutuzumab (VO) has demonstrated efficacy in both fit and unfit patients in clinical trials, yet real-world data remain limited. This retrospective, multicenter study analyzed disease- and patient-related factors affecting VO management and outcomes in 271 patients. Fitness was assessed using comorbidity indices (CLL-CI, CIRS, CCI), ECOG-PS, and caregiver need. Adverse events (AEs) and treatment modifications were evaluated across four treatment phases. Median age was 66 years (19% ≥75); 83% had comorbidities, 34% required polypharmacy, and 10% needed caregiver support. Overall, 96% completed debulking, 89% the full regimen, while 11% discontinued due to toxicity (Tox-DTD). Grade ≥3 AEs occurred in 55%, tumor lysis syndrome in 6%, severe infusion-related reactions in 5%. Overall, 3.3% died during treatment. Unfit patients did not show a significantly higher risk of treatment modifications due to AEs. Dose adjustments were more frequent during debulking. None of the validated fitness scores predicted treatment feasibility or Tox-DTD. Global feasibility was impacted by age (p .002), prior malignancies (p .003), prolonged steroid pre-treatment (p.

查看原文本刊更多论文

重新思考venetoclaxa -obinutuzumab治疗慢性淋巴细胞白血病的可行性和安全性：非传统因素可能在临床实践中发挥作用。

在慢性淋巴细胞白血病（CLL）中，新药物的适应度概念仍然存在争议。合并症和治疗相关的后勤越来越被认为是治疗可行性的关键因素。在临床试验中，Venetoclax-obinutuzumab （VO）已证明对适合和不适合的患者都有效，但实际数据仍然有限。这项回顾性、多中心研究分析了271例影响VO管理和预后的疾病和患者相关因素。使用合并症指数（CLL-CI、CIRS、CCI）、ECOG-PS和照顾者需求评估健康状况。不良事件（ae）和治疗修改在四个治疗阶段进行评估。中位年龄66岁（19%≥75岁）；83%有合并症，34%需要多种药物治疗，10%需要护理人员支持。总的来说，96%的患者完成了减积，89%的患者完成了整个治疗方案，而11%的患者因毒性（Tox-DTD）而停止治疗。≥3级不良反应发生率为55%，肿瘤溶解综合征发生率为6%，严重输液相关反应发生率为5%。总体而言，3.3%的患者在治疗期间死亡。不适合的患者由于不良事件而改变治疗的风险没有明显增加。减体积期间，剂量调整更为频繁。验证的适应度评分均不能预测治疗的可行性或Tox-DTD。总体可行性受年龄（p. 002）、既往恶性肿瘤（p. 003）、延长类固醇预处理时间（p. 003）的影响。

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

Haematologica 医学-血液学

CiteScore

14.10

自引率

2.00%

发文量

349

审稿时长

3-6 weeks

期刊介绍： Haematologica is a journal that publishes articles within the broad field of hematology. It reports on novel findings in basic, clinical, and translational research. Scope: The scope of the journal includes reporting novel research results that: Have a significant impact on understanding normal hematology or the development of hematological diseases. Are likely to bring important changes to the diagnosis or treatment of hematological diseases.