Efficacy of tazemetostat in combination with R-CHOP in elderly patients newly diagnosed with diffuse large B cell lymphoma: results of the EpiRCHOP phase II study of the LYSA.

IF 10 1区医学 Q1 MEDICINE, GENERAL & INTERNAL EClinicalMedicine Pub Date : 2025-03-18 eCollection Date: 2025-04-01 DOI:10.1016/j.eclinm.2025.103157

Clémentine Sarkozy, Thierry Jo Molina, Sydney Dubois, Cédric Portugues, Elodie Bohers, Loic Ysebaert, Roch Houot, Gian Matteo Pica, Philippe Ruminy, Charles Herbaux, Thomas Gastinne, Catherine Thieblemont, Corinne Haioun, Stéphanie Guidez, Christophe Bonnet, Gilles Crochet, Liana Veresezan, Sylvain Choquet, Emmanuel Bachy, Fabrice Jardin, Franck Morschhauser, Vincent Ribrag

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Abstract

Background: In the phase I Epi-RCHOP study (NCT02889523), we reported that R-CHOP-tazemetostat was well tolerated with the recommended phase II dose, consistent with monotherapy.

Methods: Phase II included newly diagnosed diffuse large B cell lymphoma patients aged 60-80 years who received six cycles of rituximab-CHOP (R-CHOP) with continuous tazemetostat (800 mg BID), plus two cycles of tazemetostat and rituximab (cycles 7 and 8), from July 31, 2020 to July 18, 2022. Primary endpoint was positron emission tomography complete metabolic response (CMR). Sample size was calculated with H0 of 70% and H1 assumption of 80%.

Findings: The trial enrolled 122 patients: median age 70 (60-80), 90.2% with stage III-IV, and 73.8% with International Prognostic Index 3-5. Overall, 100 patients (82%) received eight cycles, while 22 had premature treatment discontinuation (PTD), including 12 during the first two cycles. Reasons for PTD were consent withdrawal (N = 10), adverse events (N = 6), death (N = 2), protocol deviation (N = 2), progressive disease (N = 1), and physician decision (N = 1). The median percentage of relative dose intensity of tazemetostat and R-CHOP exceeded 90%, but required a protocol amendment and reduction in vincristine dosage at 1 mg full dose. At the end of treatment or PTD, 92/122 patients (75.4%) achieved CMR, eight (6.6%) partial metabolic response, five (4.1%) progressive disease, two (1.6%) died (septic shock), and 15 (12.3%) were not evaluated. Sensitivity analysis, excluding ten non-evaluated patients who withdrew consent, showed CMR in 82.1%. After a median follow-up of 18.5 months (IQR: 15.4-21), estimated progression-free and overall survival at 18 months were 77.7% (95% CI: 67.5-85.1%) and 88.8% (95% CI: 79.9-93.9%), respectively.

Interpretation: R-CHOP plus tazemetostat is feasible with a promising CMR in elderly DLBCL patients. Complementary biomarker studies are needed for a more personalized approach.

Funding: This study was sponsored under a grant from Ipsen.

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他泽他司他联合R-CHOP治疗老年新诊断弥漫性大B细胞淋巴瘤的疗效：EpiRCHOPⅱ期研究结果

背景：在I期Epi-RCHOP研究（NCT02889523）中，我们报道了R-CHOP-tazemetostat在推荐的II期剂量下耐受性良好，与单药治疗一致。方法：II期纳入新诊断的60-80岁弥漫性大B细胞淋巴瘤患者，从2020年7月31日至2022年7月18日，接受6个周期的利妥昔单抗- chop （R-CHOP）联合连续他泽美他汀（800 mg BID），加上2个周期的他泽美他汀和利妥昔单抗（第7和第8周期）。主要终点为正电子发射断层扫描完全代谢反应（CMR）。以H0为70%，H1假设为80%计算样本量。结果：该试验纳入122例患者：中位年龄70岁（60-80岁），90.2%为III-IV期，73.8%为国际预后指数3-5。总体而言，100名患者（82%）接受了8个周期，而22名患者过早停止治疗（PTD），其中12名患者在前两个周期。PTD的原因包括同意退出（N = 10）、不良事件（N = 6）、死亡（N = 2）、方案偏离（N = 2）、疾病进展（N = 1）和医生决定（N = 1）。他zemetostat和R-CHOP的相对剂量强度的中位数百分比超过90%，但需要修改方案并减少全剂量1mg的vincristine剂量。在治疗或PTD结束时，92/122例患者（75.4%）达到CMR， 8例（6.6%）部分代谢反应，5例（4.1%）疾病进展，2例（1.6%）死亡（感染性休克），15例（12.3%）未进行评估。敏感性分析，排除10名撤回同意的非评估患者，显示CMR为82.1%。中位随访18.5个月后（IQR: 15.4-21）， 18个月时估计无进展生存期和总生存期分别为77.7% （95% CI: 67.5-85.1%）和88.8% （95% CI: 77.9 -93.9%）。结论：R-CHOP联合他zemetostat对老年DLBCL患者的CMR是可行的。补充的生物标志物研究需要更个性化的方法。资助：本研究由Ipsen公司资助。

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来源期刊

EClinicalMedicine Medicine-Medicine (all)

CiteScore

18.90

自引率

1.30%

发文量

506

审稿时长

22 days

期刊介绍： eClinicalMedicine is a gold open-access clinical journal designed to support frontline health professionals in addressing the complex and rapid health transitions affecting societies globally. The journal aims to assist practitioners in overcoming healthcare challenges across diverse communities, spanning diagnosis, treatment, prevention, and health promotion. Integrating disciplines from various specialties and life stages, it seeks to enhance health systems as fundamental institutions within societies. With a forward-thinking approach, eClinicalMedicine aims to redefine the future of healthcare.