Background
Phase II, open-label, single-arm pivotal study. 102 patients with relapsed or refractory classical Hodgkin lymphoma (cHL) after failure of autologous stem cell transplantation (ASCT). Patients had received a median of 3.5 prior therapies. CD30 expression not formally required for eligibility as cHL is uniformly CD30-positive.
Interventions and follow up
Regimen: Brentuximab vedotin 1.8 mg/kg IV every 3 weeks (max 16 cycles) in R/R classical Hodgkin lymphoma after autoSCT
Primary endpoint: Objective response rate (ORR) by independent review committee
Median follow up: 18.5 months at primary analysis; long-term follow-up (Chen et al, Blood 2016)
Primary endpoint: Objective response rate (ORR) by independent review committee
Median follow up: 18.5 months at primary analysis; long-term follow-up (Chen et al, Blood 2016)
Results
ORR: 75% (95% CI 65–83)
CR rate: 34%
PR rate: 41%
Median PFS: 5.6 months
Median OS (long-term follow-up): 40.5 months (Chen et al, Blood 2016)
CR duration: median 20.5 months; 5-yr OS in CR patients ~64%
CR rate: 34%
PR rate: 41%
Median PFS: 5.6 months
Median OS (long-term follow-up): 40.5 months (Chen et al, Blood 2016)
CR duration: median 20.5 months; 5-yr OS in CR patients ~64%
Adverse events
Neurologic: peripheral neuropathy any grade 42%; grade ≥3 8% (majority reversible)
Hematologic: neutropenia grade ≥3 20%
Constitutional/GI: nausea 42%, fatigue 41%, diarrhea 38%
Tolerability: no treatment-related deaths; dose reductions in 9%; discontinuations for AE in 18%
Hematologic: neutropenia grade ≥3 20%
Constitutional/GI: nausea 42%, fatigue 41%, diarrhea 38%
Tolerability: no treatment-related deaths; dose reductions in 9%; discontinuations for AE in 18%
Conclusions
BV demonstrated a 75% ORR with 34% CR rate in heavily pretreated R/R cHL after ASCT failure, leading to FDA accelerated approval on August 19, 2011 — the first new drug approved for Hodgkin lymphoma in over 30 years. The CR rate and durable responses in a subset established BV as a landmark therapy for R/R cHL.
Key Limitations
Single-arm phase II without a comparator arm, limiting causal efficacy inference. Median PFS was short (5.6 months), indicating most responses were not durable as monotherapy; durable benefit was confined to the CR subset. The heavily pretreated post-ASCT population (median 3.5 prior lines) limits generalizability to earlier-line use. Subsequent randomized data (KEYNOTE-204) showed pembrolizumab superior to BV monotherapy in R/R cHL, and BV is now most often used in combination rather than as a single agent.
Clinical Context
This pivotal trial established BV as the first targeted anti-CD30 ADC for R/R cHL, supporting FDA accelerated approval (August 2011) after ASCT failure. BV has since become a backbone of cHL therapy across lines, including frontline BV+AVD (ECHELON-1) and salvage BV+nivolumab. In R/R single-agent use, pembrolizumab subsequently demonstrated superior PFS (KEYNOTE-204), and ESMO/ASCO guidance now positions PD-1 blockade and BV-based combinations ahead of BV monotherapy in many R/R settings.