According to efficacy results of the phase 2 TAZ R-CHOP study, R-CHOP plus tazemetostat, a selective oral EZH2 inhibitor, is a feasible treatment option among older patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL).

At the 2023 American Society of Hematology (ASH) Annual Meeting and Exposition in San Diego, CA, Clementine Sarkozy, MD, Hematology Department, Institut Curie, Paris, France, reported these trial results. 

From July 31, 2020, to July 18, 2022, 122 patients were enrolled in 27 LYSA centers. Mutational profile was available for 76 patients, of whom 10 had an EZH2 mutation and 26 had an EZB profile as assessed with the LymphGen classifier. The primary end point was PET-based complete metabolic response (CR) rate at the end of study treatment, defined as 8 cycles or at time of permanent treatment discontinuation. The key secondary objectives were progression free survival (PFS) and overall survival (OS).

Trial participants received 6 R-CHOP every 21 days in combination with continuous tazemetostat at 800 mg two times per day, in addition to 2 cycles of tazemetostat and rituximab (cycle 7 and 8). Investigators noted that for prophylaxis with granulocyte colony stimulating factor (G-CSF), valaciclovir and trimethoprim sulfamethoxazole were strongly recommended. In this study, 100 patients received 8 cycles and 22 patients had a premature treatment discontinuation (PTD); 12 during the first 2 cycles and 10 between cycles 3 and 8. Overall, the median percentage of tazemetostat dose received was 98.4%. Adverse events led to tazemetostat interruption in 4.1%, discontinuation in 2.8% and dose reduction in 2.4% of the cases. The mean time between cycles was 21.5 days. 

At end of treatment or PTD, 92 out of 122 patients achieved CR, 8 (6.6%) achieved partial response (PR), 5 (4.1%) had progressive disease, 2 (1.6%) had died from septic shock and 15 (12.3%) were not evaluated and considered as non-responders. Results demonstrated that the primary objective was not met in this efficacy set, with a CR of 75.4% (lower than the H1 at 80%). After a median follow-up of 18.5 months, 17 out of 122 patients had a relapse/progression and 12 had died. The estimated 18-month PFS and OS were 77.7% and 88.8% respectively.

In terms of safety, the most common adverse events were: neutropenia (53%), anemia (51%), nausea (47%), asthenia (42%), peripheral neuropathy (37%), gastro-intestinal hypomotility (35%), weight loss (28%), vomiting (24%), and thrombocytopenia (24%). Additionally, adverse events of grade 3 or more occurred in 73% of patients and were mainly hematological with neutropenia (48%, including 6% of febrile neutropenia), anemia (23%), thrombocytopenia (17%) and gastro-intestinal disorder (overall 10.7%). Red blood cell and platelets transfusions were administered in 31% and 11.5% of the patients, respectively.

Dr Sarkozy and colleagues concluded that R-CHOP plus tazemetostat is an achievable treatment option among patients with newly diagnosed diffuse large B-cell lymphoma.

“Efficacy results in this trial conducted during the COVID pandemic in a particularly challenging population, suggest that the combination warrant[s] further investigation including correlative studies with molecular subclassification that will be presented,” they added.

Source:

Sarkozy C, Molina TJ, Houot R, et al. Results of the phase II of epirchop study, evaluating the efficacy of tazemetostat in combination with R-CHOP in elderly newly diagnosed diffuse large B-cell lymphoma (DLBCL): A lysa study; December 9-12, 2023; San Diego, CA. Abstract 853