Frontline Tazemetostat May Induce Complete Metabolic Response in FL

Among patients with high-risk follicular lymphoma (FL), frontline tazemetostat with R-CHOP (cyclophosphamide, doxorubicin, vincristine, rituximab, and prednisone) may induce a high complete metabolic response rate, according to research presented at the ASH Annual Meeting 2023. There was, however, a high rate of adverse events (AEs) prior to reduction in vincristine dose noted with this combination.

Previous research has suggested that tazemetostat, an EZH2 inhibitor, may be effective for treating some patients with FL. The drug was approved by the US Food and Drug Administration for patients with relapsed or refractory disease, among those with EZH2 mutations, and for patients who had received at least 2 prior therapies.

The Epi-RCHOP study (ClinicalTrials.gov Identifier: NCT02889523) was developed to investigate the safety and efficacy of tazemetostat with R-CHOP maintenance among previously untreated patients with high-risk FL. At the ASH Annual Meeting 2023, the authors presented the results from the phase 2 part of Epi-RCHOP.

Overall, 62 patients were enrolled and treated between 2020 and 2022. At baseline, 61.3% of patients were male, the median age was 64.5 years, 17.3% of patients had an EZH2 mutation, and 68.3% of patients had bone marrow involvement.

The median follow-up was 19 months. Overall, 93% of patients completed induction and initiated maintenance period 1; 71% of patients initiated maintenance period 2. By end of induction, 79% (95% CI, 66.8-88.3) of patients had a complete metabolic response; the overall metabolic response rate was 95.2%. Per protocol, however, because 16 patients with a complete metabolic response had no bone marrow biopsy data available, their responses were revised to a partial response — this led to a revised complete response rate of 53.2%.

The median 18-month progression-free and overall survival rates were 89.3% and 98.3%, respectively. Median progression-free survival and duration of response were not reached. Eight (88.9%) of the 9 patients with an EZH2 mutation had a complete response, compared with 45.9% of patients with wild-type (P =.027).

The most frequently noted grade 3 or worse treatment-related AEs were (53.2%; 3.2% of which were febrile), thrombocytopenia (17.7%), and anemia (16.1%). The researchers subsequently modified the vincristine dose, after which 30 digestive AEs were noted.

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, or device companies. Please see the original reference for a full list of disclosures.