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.

in EClinicalMedicine by 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

TLDR

  • The phase II study found that R-CHOP plus tazemetostat was well-tolerated and effective in treating newly diagnosed DLBCL patients aged 60-80 years, with a promising CMR rate.

Abstract

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. 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%. 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. R-CHOP plus tazemetostat is feasible with a promising CMR in elderly DLBCL patients. Complementary biomarker studies are needed for a more personalized approach. This study was sponsored under a grant from Ipsen.

Overview

  • The study aimed to evaluate the safety and efficacy of R-CHOP plus tazemetostat in newly diagnosed diffuse large B cell lymphoma (DLBCL) patients aged 60-80 years.
  • The study was a phase II clinical trial that enrolled 122 patients who received six cycles of R-CHOP with continuous tazemetostat, plus two cycles of tazemetostat and rituximab.
  • The primary endpoint was positron emission tomography (PET) complete metabolic response (CMR) at the end of treatment or premature treatment discontinuation (PTD).

Comparative Analysis & Findings

  • The study found that 92 out of 122 patients (75.4%) achieved CMR at the end of treatment or PTD, and 82.1% achieved CMR after excluding 10 patients who withdrew consent.
  • The 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.

Implications and Future Directions

  • The study suggests that R-CHOP plus tazemetostat is a feasible treatment option for elderly DLBCL patients, with a promising CMR rate.
  • Future studies should aim to identify biomarkers to personalize this treatment approach for individual patients.
  • The study highlights the importance of further clinical trials to confirm the efficacy and safety of R-CHOP plus tazemetostat in this patient population.
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