The combination of chidamide with the CHOEP regimen in previously untreated patients with peripheral T-cell lymphoma: a prospective, multicenter, single arm, phase 1b/2 study.

Objective: To assess the efficacy and safety of the novel histone deacetylase inhibitor, chidamide, in combination with cyclophosphamide,doxorubicin, vincristine, etoposide, and prednisone (Chi-CHOEP) for untreated peripheral T-cell lymphoma (PTCL). Methods: A prospective, multicenter, single arm, phase 1b/2 study was conducted. A total of 128 patients with untreated PTCL (18–70years of age) were enrolled between March 2016 and November 2019, and treated with up to 6 cycles with the Chi-CHOEP regimen.In the phase 1b study, 3 dose levels of chidamide were evaluated and the primary endpoint was determination of the maximumtolerateddose and recommended phase 2 dose (RP2D). The primary endpoint of the phase 2 study was 2-year progression-freesurvival (PFS). Results: Fifteen patients were enrolled in the phase 1b study and the RP2D for chidamide was determined to be 20 mg, twice aweek. A total of 113 patients were treated at the RP2D in the phase 2 study, and the overall response rate was 60.2%, with a completeresponse rate of 40.7%. At a median follow-up of 36 months, the median PFS was 10.7 months, with 1-, 2-, and 3-year PFS ratesof 49.9%, 38.0%, and 32.8%, respectively. The Chi-CHOEP regimen was well-tolerated, with grade 3/4 neutropenia occurring inapproximately two-thirds of the patients. No unexpected adverse events (AEs) were reported and the observed AEs were manageable. Conclusions: This large cohort phase 1b/2 study showed that Chi-CHOEP was well-tolerated with modest efficacy in previouslyuntreated PTCL patients.