Background
Peripheral T-cell lymphoma (PTCL) is aggressive and chemotherapy-resistant, with CHOP yielding poor durable outcomes. ECHELON-2 tested whether replacing vincristine with brentuximab vedotin (anti-CD30 ADC; A+CHP) improves outcomes in CD30-positive PTCL.
Interventions and follow up
Arm A: A+CHP — brentuximab vedotin + cyclophosphamide + doxorubicin + prednisone, every 21 days x6-8 cycles
Arm B: CHOP — cyclophosphamide + doxorubicin + vincristine + prednisone, every 21 days x6-8 cycles
Population: N=452, untreated CD30+ PTCL (70% systemic ALCL, 13% AITL, 6% PTCL-NOS)
Primary endpoint: PFS by blinded independent review
Median follow-up: 36.2 months
Arm B: CHOP — cyclophosphamide + doxorubicin + vincristine + prednisone, every 21 days x6-8 cycles
Population: N=452, untreated CD30+ PTCL (70% systemic ALCL, 13% AITL, 6% PTCL-NOS)
Primary endpoint: PFS by blinded independent review
Median follow-up: 36.2 months
Results
Median PFS: 48.2 vs 20.8 months (HR 0.71, 95% CI 0.54–0.93, P=.011)
Median OS: not reached vs 17.5 months estimate (HR 0.66, 95% CI 0.46–0.95, P=.024)
Objective response: 83% vs 72%; complete response 68% vs 56%
Subgroups: benefit driven predominantly by ALCL (ALK+ and ALK-)
Median OS: not reached vs 17.5 months estimate (HR 0.66, 95% CI 0.46–0.95, P=.024)
Objective response: 83% vs 72%; complete response 68% vs 56%
Subgroups: benefit driven predominantly by ALCL (ALK+ and ALK-)
Adverse events
Overall: Grade 3-4 AEs comparable (~66% vs ~65%)
Hematologic: neutropenia 35% vs 39%; febrile neutropenia 18% vs 15%
Neurologic: peripheral neuropathy any grade 52% vs 55% (mostly grade 1-2, reversible)
Other: no excess serious infections; AE-related discontinuation comparable
Hematologic: neutropenia 35% vs 39%; febrile neutropenia 18% vs 15%
Neurologic: peripheral neuropathy any grade 52% vs 55% (mostly grade 1-2, reversible)
Other: no excess serious infections; AE-related discontinuation comparable
Conclusions
A+CHP significantly improved PFS and OS over CHOP in CD30+ PTCL — the first phase III regimen to show an OS benefit in this setting — establishing A+CHP as standard of care, particularly for systemic ALCL.
Key Limitations
Benefit driven by ALCL subtype; non-ALCL PTCL subtypes (AITL, PTCL-NOS) underpowered and benefit uncertain; CD30 expression ≥1% required (excludes CD30-negative PTCL); no consolidation-ASCT comparison; limited data in rarer PTCL entities.
Clinical Context
FDA approved brentuximab vedotin + CHP for previously untreated systemic ALCL and other CD30-expressing PTCL in 2018; EMA approved 2019. ESMO/ASCO guidance positions A+CHP as preferred frontline therapy for CD30+ PTCL, especially ALCL; CHOP/CHOEP remains used for CD30-negative subtypes.