Background
ABVD was the long-standing frontline standard for advanced Hodgkin lymphoma but carried bleomycin-related pulmonary toxicity. ECHELON-1 tested whether replacing bleomycin with brentuximab vedotin (anti-CD30 ADC; A+AVD) improves outcomes in previously untreated stage III/IV classic Hodgkin lymphoma.
Interventions and follow up
Arm A: A+AVD — brentuximab vedotin 1.2 mg/kg + doxorubicin + vinblastine + dacarbazine, every 2 weeks x6 cycles
Arm B: ABVD — doxorubicin + bleomycin + vinblastine + dacarbazine, every 2 weeks x6 cycles
Population: N=1334, untreated stage III/IV cHL
Primary endpoint: modified PFS by independent review
Median follow-up: 24.6 months (primary); 73 months (updated OS)
Arm B: ABVD — doxorubicin + bleomycin + vinblastine + dacarbazine, every 2 weeks x6 cycles
Population: N=1334, untreated stage III/IV cHL
Primary endpoint: modified PFS by independent review
Median follow-up: 24.6 months (primary); 73 months (updated OS)
Results
2-yr modified PFS: 82.1% vs 77.2% (HR 0.77, 95% CI 0.60–0.98, P=.03)
6-yr OS (updated): 93.9% vs 89.4% (HR 0.59, 95% CI 0.40–0.88, P=.009)
Subgroups: benefit greatest in stage IV disease
Comparison: first regimen to show OS superiority over ABVD in advanced HL
6-yr OS (updated): 93.9% vs 89.4% (HR 0.59, 95% CI 0.40–0.88, P=.009)
Subgroups: benefit greatest in stage IV disease
Comparison: first regimen to show OS superiority over ABVD in advanced HL
Adverse events
Hematologic: Grade 3-4 neutropenia 58% vs 45%; febrile neutropenia 19% vs 8% (mitigated by G-CSF primary prophylaxis)
Neurologic: peripheral neuropathy any grade 67% vs 43% (most resolved/improved)
Pulmonary: pulmonary toxicity 2% vs 7% (bleomycin-related toxicity markedly reduced)
Neurologic: peripheral neuropathy any grade 67% vs 43% (most resolved/improved)
Pulmonary: pulmonary toxicity 2% vs 7% (bleomycin-related toxicity markedly reduced)
Conclusions
A+AVD improved modified PFS and, on long-term follow-up, OS versus ABVD in advanced Hodgkin lymphoma while eliminating bleomycin pulmonary toxicity, establishing A+AVD as a frontline standard for stage III/IV cHL.
Key Limitations
Higher neutropenia/neuropathy requiring G-CSF prophylaxis; no PET-adapted comparator arm; benefit smaller in early-stage or limited disease (not studied); subsequently challenged in frontline by N-AVD (S1826); cost of brentuximab vedotin.
Clinical Context
FDA expanded brentuximab vedotin (with AVD) to frontline stage III/IV cHL in 2018; EMA followed. A+AVD became an ESMO/ASCO-endorsed frontline standard. It has since been challenged by nivolumab-AVD (S1826), which showed superior PFS over A+AVD with less neuropathy.