Tazemetostat Yields Durable Responses in Patients with FL
Tazemetostat yielded durable responses and was generally well tolerated in a recent study of heavily pretreated patients with relapse or refractory follicular lymphoma (FL; Lancet Oncol. 2020 Oct 6. Epub ahead of print).
According to lead investigator Franck Morschhauser, MD, PhD, professor of hematology, University of Lille, Lille, France, and colleagues, approximately 20% of patients with FL have activating mutations of EZH2, an epigenetic regulator. The study aimed to determine the activity and safety of tazemetostat, an oral EZH2 inhibitor, in patients with FL.
The primary endpoint was objective response rate (ORR) based on the 2007 International Working Group criteria for non-Hodgkin lymphoma, assessed by an independent radiology committee. Also, activity and safety analyses were completed in patients who received 1 dose or more of tazemetostat.
From July 9, 2015 to May 24, 2019, 99 patients (≥18 years) with histologically confirmed FL (grade 1, 2, 3a, or 3b) that had relapsed or was refractory to 2 or more systemic therapies, had an Eastern Cooperative Oncology Group (ECOG) score of 0-2, and had sufficient tumor tissue for central testing of EZH2 mutation status, were enrolled in the open-label, single-arm, phase 2 trial at 38 clinics and hospitals worldwide. These patients were categorized by EZH2 status: mutant (EZH2mut, n=45) or wild-type (EZH2WT, n=54).
The median follow-up was 22 months for the EZH2mut cohort and 35.9 months for the EZH2WT cohort. The ORR was 69% (95% CI, 53-82; 31 patients) in the EZH2mut cohort and 35% (95% CI, 23-49; 19 patients) in the EZH2WT cohort. The median duration of response was 10.9 months (95% CI, 7,2-NE) in the EZH2mut cohort and 13 months (95% CI, 5.6-NE) in the EZH2WT cohort. Median progression free survival (PFS) was 13.8 months (10.8-22) and 11.1 months (3.7-14.6), respectively.
Overall, 98 of 99 patients had 1 or more treatment emergent adverse events of any grade and treatment-related adverse events of grade 3 or worse severity included thrombocytopenia (3%), neutropenia (3%), and anemia (2%). Serious treatment-related events were reported in 4 patients, and there were no treatment-related deaths.—Emily Bader