EZH2 Inhibitor Safe, Active in Relapsed/Refractory FL

Tazemetostat was shown to be active in patients with follicular lymphoma (FL) in a phase 2 study, and yielded a low incidence of treatment-related adverse events (AEs; Blood. 2019;134[Suppl 1]:123).

“Relapsed/refractory [FL] remains a difficult-to-treat condition, with limited treatment options. New, tolerable treatments with unique mechanisms of action are needed, especially for high-risk patients whose disease progresses within 24 months of diagnosis (POD24),” explained Franck Morschhauser, MD, PhD, Department of Hematology, CHRU Lille, France, and colleagues.

“Tazemetostat, an investigational, selective, oral EZH2 inhibitor, has demonstrated durable, single-agent, antitumor activity in [relapsed/refractory] FL patients with [mutant] or wild-type (WT) EZH2,” they continued.

In the phase 2 study, Dr Morschhauser evaluated the use of tazemetostat 800 mg twice daily in patients with mutant or WT EZH2 relapsed or refractory FL. The primary end point of the trial was objective response rate, and secondary end points included progression-free survival (PFS) and safety.

Interim data on the efficacy and safety of tazemetostat in the mutant and WT EZH2 cohorts, as well as the POD24 subgroup, are described here.

As of June 7, 2019, interim data for 99 patients were available, including 45 patients in the mutant EZH2 cohort (POD24: n = 17 [38%]) and 54 patients with WT EZH2 (POD24: n = 30 [ 56%]).

A total of 33 patients in the mutant EZH2 cohort had an objective response, including 15 (45%), 7 (21%), and 4 (12%) patients with responses at ≥6 months, ≥12 months, and ≥16 months, respectively. A total of 18 patients in the WT EZH2 cohort had an objective response, including 15 (83%) with a response at ≥6 months, 9 (50%) with a response at ≥12 months, and 6 (33%) with a response at ≥16 months.

At the time of this analysis, the median follow-up timeframe and median PFS was 15.9 months and 11.1 months, respectively, in the mutant EZH2 cohort, and 14.5 months and 13.8 months, respectively, in the POD24 subgroup. In addition, the median follow-up timeframe was 24.9 months and the median PFS was 5.7 months in the WT EZH2 cohort, and 26 months and 5.6 months, respectively, in the POD24 subgroup.

Treatment-related AEs were reported in 17% of patients overall, and 15% in the POD24 subgroup. The most common AEs were thrombocytopenia (3%), anemia (2%), asthenia (2%), vomiting (1%), and fatigue (1%). Overall, 5% of patients discontinued treatment and 9% had dose reductions related to AEs.

“Tazemetostat was generally well tolerated, with a low incidence of treatment-related AEs,” Dr Morschhauser and colleagues concluded.

“Tazemetostat demonstrated clinically meaningful, durable, single-agent activity across a spectrum of patients with FL, including the POD24 subgroup, and pronounced responses in patients with EZH2 activating mutations,” they added.—Janelle Bradley