ROMIDEPSIN PLUS CHOP VERSUS CHOP IN PATIENTS WITH PREVIOUSLY UNTREATED PERIPHERAL T‐CELL LYMPHOMA: FINAL ANALYSIS OF THE RO‐CHOP TRIAL

Introduction: The primary analysis of the Ro-CHOP trial (NCT01796002) demonstrated that romidepsine (Ro) plus CHOP did not provide an increased efficacy compared with CHOP alone in patients with previously untreated peripheral T-cell lymphoma (PTCL). We report here the final analysis of the Ro-CHOP trial.Methods: The study was an open-label multicenter randomized (1:1) phase III study of Ro-CHOP versus CHOP as frontline treatment of patients 18–80 years with PTCL. The primary endpoint was progression-free survival (PFS) according to IWG 1999 criteria. Overall survival (OS) was a secondary endpoint, relapse patterns and PFS/OS after the first progression (PFS2/OS2) were analyzed post-hoc. The cut-off date was set to 2022/12/13, that is, five years after the last patient was enrolled.Results: 211 and 210 patients were assigned to receive 6 cycles of Ro-CHOP or CHOP in 3-week cycles, respectively. Median age was 65 (25–81) years. With a median follow-up of 71.8 months, 271 patients (64.4%) presented a PFS event by independent RAC assessment. Median PFS was 12 months (95% CI = [9; 25.8]) and 10.2 months ([7.4; 13.2]) for Ro-CHOP and CHOP, respectively (HR = 0.79 [0.62; 1.005], p = 0.054, 2-sided p-value). Based on 229 deaths, median OS was 62.2 months and 43.8 months for Ro-CHOP and CHOP, respectively. The causes of death were the following: lymphoma (n = 165, 72.4%), concurrent illness (n = 30, 13.2%), other reasons (n = 12, 5.3%), toxicity of salvage treatment (n = 8, 3.5%), toxicity of study treatment (n = 4, 1.8%), unknown (n = 9, 3.9%). No new safety signal was observed.A significantly prolonged PFS in the follicular helper T-cell (TFH) lymphoma subgroup (centrally reviewed) was still observed with this longer follow-up. The median PFS was 19.5 months ([11.5; 44.4]) in the Ro-CHOP arm and 10.6 months ([7.4; 14.9) the CHOP arm with a HR of 0.703 ([0.502; 0.985], p = 0.0395).Additional treatment was given to 251 patients after progression (Ro-CHOP = 115, and CHOP = 136), leading to an overall response rate of 35.7% (CR/CRu: 21.7%) and 31.6% (CR/CRu: 22.1%) in the Ro-CHOP and CHOP groups, respectively. Overall, 191 of the 251 patients (76.1%) progressed after second-line therapy, and 20 patients died without a second progression (8.0%). The median PFS2 and OS2 were 3.3 months (95% CI, [2.7; 4.5]) and 11.5 months ([9.6; 15.9]), respectively. Twenty-three patients (9.2%) received an allogeneic stem cell transplantation (median age 51 [29–70] years) and display