CHEPA Regimen Achieves 76% Complete Metabolic Response in CD30-Positive PTCL: Phase 2 Trial Results Presented at EHA 2026
核心洞察
The Phase 2 CHEPA trial combining brentuximab vedotin with CHP plus etoposide met its primary endpoint with a 76% complete metabolic response rate in frontline CD30 (搜索)-positive PTCL.
Patients with ALCL achieved 100% two-year PFS and OS, while non-ALCL subtypes showed 62% PFS and 84% OS at a median follow-up of 29.6 months.
ctDNA analysis revealed plasma samples were more informative than tumor tissue for detecting TCR clones (87% vs 77%) and tumor-specific mutations (91% vs 81%).
The prospective multicenter single-arm Phase 2 CHEPA trial (NCT05006664) has met its primary endpoint, demonstrating a 76% complete metabolic response (CMR) rate at the end of treatment in patients with previously untreated CD30 (搜索)-positive peripheral T-cell lymphoma (搜索) (PTCL). The results were presented by Marek Trněný at the European Hematology Association (EHA) 2026 Congress, alongside exploratory circulating tumor DNA (ctDNA) analyses that suggest plasma-based molecular profiling may outperform tumor tissue sampling in this disease.
The trial, conducted by the Czech Lymphoma Study Group (搜索) (CLSG), enrolled 33 patients between February 2022 and August 2025, all of whom completed the planned six cycles of CHEPA. The overall response rate (ORR) reached 91%, reinforcing the potential of this brentuximab vedotin-based quadruplet regimen as a frontline strategy.
Rationale and Study Design
PTCLs are rare, heterogeneous, and generally aggressive mature T-cell neoplasms associated with dismal clinical outcomes. The incorporation of brentuximab vedotin into cyclophosphamide, doxorubicin, and prednisone (BV-CHP) has improved survival outcomes and established a new treatment standard for CD30 (搜索)-positive disease, yet relapse remains common. Previous studies suggested that adding etoposide to CHOP (CHOEP) may improve outcomes, particularly in younger and fit patients, providing the rationale for the CHEPA combination.
The CHEPA regimen consisted of brentuximab vedotin (1.8 mg/kg), cyclophosphamide (750 mg/m²), and doxorubicin (50 mg/m²) on day 1; etoposide (100 mg/m²) on days 1–3; and prednisone (100 mg daily) on days 1–5, administered every 21 days for six cycles. Following induction, patients proceeded to either follow-up or high-dose therapy with autologous stem cell transplantation (ASCT) per study plan.
The median age was 58 years, with 67% of patients being male and all having an ECOG performance status of 0–1. Advanced-stage disease was present in 79% of patients, while elevated LDH levels and bone marrow involvement were observed in 58% and 30%, respectively.
Efficacy Outcomes by Histologic Subtype
The study population comprised 14 patients with anaplastic large cell lymphoma (搜索) (ALCL, 42%) and 19 with non-ALCL PTCL (58%), including PTCL-NOS (27%), nodal T-follicular helper (nTFH) lymphoma (27%), and enteropathy-associated T-cell lymphoma (3%).
At a median follow-up of 29.6 months, outcomes diverged significantly by histology. Patients with ALCL achieved a 2-year progression-free survival (PFS) of 100%, compared with 62% in the non-ALCL cohort (p=0.012). Two-year overall survival (OS) was 100% in ALCL patients and 84% in those with non-ALCL disease.
Treatment delivery was favorable across the cohort, with all 33 patients completing six planned cycles. Twenty-one patients had preplanned ASCT, and 16 had undergone transplantation at the time of analysis. The relative dose intensity remained high across all treatment components, with median values of approximately 95%.
Safety Profile
Grade 3–4 adverse events occurred in 81.8% of patients, predominantly hematologic in nature, including neutropenia, thrombocytopenia, febrile neutropenia, and anemia. Notably, no grade 3–4 peripheral neuropathy and no grade 5 adverse events were reported, a finding of particular importance given that one-third of patients were older than 60 years.
ctDNA Profiling: Plasma Outperforms Tissue
Exploratory ctDNA analyses employed CAPP-Seq targeting 259 recurrently mutated T-cell lymphoma genes, while clonotypic VDJ sequences across T-cell receptor loci were assessed using SABER. Baseline ctDNA profiling identified recurrent genomic alterations characteristic of PTCL biology, with TET2 (搜索), DNMT3A (搜索), RHOA (搜索), and STAT3 (搜索) among the most frequently mutated genes.
A key finding was that plasma samples appeared more informative than tumor tissue for molecular profiling. Plasma detected TCR clones in 87% of available samples versus 77% for tumor tissue, and identified tumor-specific mutations in 91% versus 81%. Combined assessment of plasma and tissue enabled molecular disease monitoring in all evaluable patients. Ongoing analyses will further explore the role of ctDNA-based measurable residual disease (MRD) assessment and its potential prognostic value.
Clinical Implications
The CHEPA study demonstrates that adding etoposide to the BV-CHP backbone yields a high rate of complete metabolic responses with a manageable safety profile in CD30 (搜索)-positive PTCL. The 100% 2-year PFS and OS observed in ALCL patients are particularly encouraging, though the 62% PFS in non-ALCL subtypes underscores the continued unmet need in this heterogeneous population. Longer follow-up is warranted, especially given the predominance of non-ALCL subtypes in the study cohort.