Brentuximab vedotin plus cyclophosphamide, doxorubicin, etoposide, and prednisone (CHEPA) in newly diagnosed CD30-positive peripheral T-cell lymphomas with integrated ctDNA analysis: Results of the phase 2 CHEPA trial.

Abstract

7081 Background: Peripheral T-cell lymphomas (PTCLs) are aggressive malignancies associated with poor outcomes. While adding brentuximab vedotin (BV) to CHP has improved results in CD30+ PTCL, relapses remain common. Given the suggested benefit of etoposide (CHOEP) in younger patients, the prospective multicenter single-arm Phase 2 CHEPA study (NCT05006664) was conducted to evaluate the efficacy and safety of CHEPA (BV-CHEP) induction combined with circulating tumor DNA (ctDNA) analysis. Methods: Patients with previously untreated CD30+ PTCL eligible for autologous stem cell transplantation (ASCT) were enrolled. Treatment consisted of 6 cycles of CHEPA (D1: BV 1.8 mg/kg, cyclophosphamide 750 mg/m², doxorubicin 50 mg/m²; D1–3: etoposide 100 mg/m²; D1–5: prednisone 100 mg/d) every 21 days. The primary endpoint was the complete metabolic response (CMR) rate at the end of treatment (EOT). Secondary endpoints included safety, PFS, OS, ORR, and exploratory ctDNA analysis. Plasma cfDNA was profiled using CAPP-Seq (259 genes) and clonotypic VDJ sequencing at all TCR loci via SABER. Results: Between 05/2022 and 09/2025, 40 patients were screened; 33 met eligibility criteria and initiated therapy. The cohort included 14 (42%) ALCL and 19 (58%) non-ALCL cases (median age 57 years, range 26–69). Baseline characteristics showed a predominance of males (67%), advanced-stage disease (79%), elevated LDH (58%), and bone marrow involvement (30%); all pts had an ECOG PS of 0–1. All 33 pts completed 6 cycles of CHEPA. At EOT, 25/33 (76%) achieved CMR, meeting the primary endpoint. The ORR was 91% for the entire cohort (CMR: 86% for ALCL, 68% for non-ALCL). ASCT was preplanned in 21/33 pts and has been performed to date in 14 pts. At a median follow-up of 19 months, the 18-month PFS and OS probabilities were 75% and 92%, resp. Specifically, PFS was 100% for ALCL vs. 59% for non-ALCL, while OS was 100% vs. 87%. Age and bone marrow involvement were the only baseline variables significantly associated with CMR. Baseline ctDNA burden was significantly correlated with total metabolic tumor volume (r=0.68, p<0.001), LDH level (r=0.48, p=0.03), and PIT (p<0.05). Grade 3–4 adverse events occurred in 82% of pts, primarily hematological: neutropenia (79%), thrombocytopenia (18%), febrile neutropenia (15%), and anemia (15%). No grade 3–4 peripheral neuropathy or grade 5 events were reported. Conclusions: The CHEPA study met its primary endpoint with a 76% CMR rate. Despite limited follow-up and high non-ALCL prevalence of our cohort, PFS and OS results are promising. Toxicity was manageable with no treatment-related deaths even though 33% of patients were >60 years old, supporting the safety of adding etoposide to the BV-CHP backbone. Further investigation of outcomes based on EOT MRD by ctDNA is ongoing. Clinical trial information: NCT05006664 .