Epi-RCHOP phase II results: Tazemetostat in combination with R-CHOP in newly diagnosed DLBCL

Tazemetostat (Taz) is a selective oral EZH2 inhibitor approved by the US Food and Drug Administration for FL. Taz has demonstrated a favorable safety profile as a single agent in DLBCL. Phase I of the Epi-RCHOP trial (NCT02889523) reported that Taz in combination with R-CHOP was well tolerated and had comparable pharmacokinetic results with those of R-CHOP alone. The results from phase II of the Epi-RCHOP trial evaluating the efficacy and safety of Taz + R-CHOP in elderly patients with newly diagnosed DLBCL were recently published by Sarkozy et al. in eClinicalMedicine.¹ 

Eligible patients were aged between ≥60 and ≤80 years with a diagnosis of untreated DLBCL (N = 122). Patients received up to 6 cycles of R-CHOP every 28 days in combination with continuous Taz at 800 mg BID, followed by 2 cycles of Taz and rituximab. The primary endpoint was PET-assessed complete metabolic response (CMR) rate. Key secondary endpoints included PFS, DOR, and OS. The median follow-up was 18.5 months (range 0.2–28.1 months).

Key learnings

At EOT or PTD, 75.4% and 6.6% of patients in the efficacy set (N = 122) achieved CMR and PMR, respectively. In the sensitivity set (n = 112), 82.1% and 7.1% of patients achieved CMR and PMR, respectively.

The estimated PFS and OS were 77.7% and 88.8%, respectively, in the safety set (N = 122). The ORR was 82.0% and 89.3% in the safety and sensitivity sets, respectively.

The most frequent Grade ≥3 hematological AEs included neutropenia (48%), anemia (23%), and thrombocytopenia (17%). SAEs were reported in 25% of patients; infection (3%) and gastrointestinal hypomotility (3%) were the most frequent SAEs.

Taz + R-CHOP demonstrated efficacy with promising CMR rates in elderly patients with DLBCL. Future long-term and complementary biomarker studies are needed for a personalized treatment approach in this population.