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
{"title":"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","authors":"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","doi":"10.1016/j.eclinm.2025.103157","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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%.</p><p><strong>Findings: </strong>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.</p><p><strong>Interpretation: </strong>R-CHOP plus tazemetostat is feasible with a promising CMR in elderly DLBCL patients. Complementary biomarker studies are needed for a more personalized approach.</p><p><strong>Funding: </strong>This study was sponsored under a grant from Ipsen.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"82 ","pages":"103157"},"PeriodicalIF":9.6000,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11957796/pdf/","citationCount":"0","resultStr":"{\"title\":\"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.\",\"authors\":\"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\",\"doi\":\"10.1016/j.eclinm.2025.103157\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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%.</p><p><strong>Findings: </strong>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.</p><p><strong>Interpretation: </strong>R-CHOP plus tazemetostat is feasible with a promising CMR in elderly DLBCL patients. 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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.
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.
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.
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