IBCL-165: Tazemetostat in Relapsed/Refractory (R/R) Follicular Lymphoma (FL): Propensity Score-Matched Analysis of E7438-G000-101 Trial Outcomes

Context Tazemetostat, an oral enhancer of zeste homolog 2 (EZH2) inhibitor, received FDA approval based on a phase 2 study (NCT01897571); in this study, the wild-type (WT) EZH2 cohort included more patients with poor-risk features than the mutant (MT) EZH2 cohort. Objective Assess outcomes in patients with WT versus MT EZH2 R/R FL after minimizing baseline characteristic differences by creating a matched sample of comparable WT and MT patients. Design In a post hoc analysis of NCT01897571, we generated propensity scores for each WT (n=54) and MT (n=45) EZH2 patient based on the likelihood of being selected, given their baseline characteristics. Characteristics prognostic for clinical outcomes with appreciable baseline differences between cohorts included ECOG performance status, number of prior anticancer therapies, progression of disease within 24 months, double-refractory status, and prior hematopoietic stem cell transplant. Patients were matched using a 1:1 nearest-neighbor approach. Baseline covariates between the matched groups were sufficiently balanced. Setting Thirty-eight global clinics/hospitals. Patients Adults with R/R FL who received ≥2 prior systemic therapies. Interventions Tazemetostat 800 mg orally in continuous 28-day cycles. Main Outcome Measures Objective response rate (ORR) estimates were measured for the matched groups. Progression-free survival (PFS) was described using Kaplan–Meier analyses. Results The propensity-matched sample included 56 patients (28 WT, 28 MT). Before matching, ORR was 35% (95% CI [22%, 48%]) in WT and 69% (95% CI [55%, 83%]) in MT EZH2 groups; after matching, ORR was 50% (95% CI [31%, 69%]) and 71% (95% CI [54%, 88%]), respectively. Median PFS was 11.1 months (95% CI [5.4, 16.7]) in WT and 13.8 months (95% CI [11.1, 22.1]) in MT prior to matching, and 14.3 months (95% CI [11.1, inf]) and 14.8 months (95% CI [10.7, inf]) in WT and MT matched groups, respectively. Conclusion As expected, efficacy remained higher in the MT group; however, after adjustment, ORR and PFS improved in the WT group. This hypothesis-generating analysis suggests that outcomes in patients with WT EZH2 R/R FL treated with tazemetostat may have been more similar to those with MT EZH2 in the phase 2 trial if baseline disease characteristics were more equally matched.