Background
CheckMate 205 was a phase II open-label single-arm study (n=243) of nivolumab in relapsed/refractory classical Hodgkin lymphoma after ASCT, across three cohorts: Cohort A (ASCT-naive, n=63), Cohort B (post-ASCT, BV-naive, n=80), Cohort C (post-ASCT, post-BV failure, n=100). Nivolumab exploits the near-universal chr9p24.1 amplification of PD-L1/PD-L2 in cHL.
Interventions and follow up
Regimen: Nivolumab 3 mg/kg IV q2w until progression or unacceptable toxicity (maximum 2 years)
Primary endpoint: ORR by independent radiology review
Median follow up: 18 months (primary analysis); extended follow-up reported
Primary endpoint: ORR by independent radiology review
Median follow up: 18 months (primary analysis); extended follow-up reported
Results
ORR (all cohorts): 69% (95% CI 63–75)
CR rate: 16%
PR rate: 53%
Median DOR: 16.6 months
Median PFS: 14.7 months
Cohort C (post-ASCT, post-BV): ORR 68%, median PFS 11.9 months
CR rate: 16%
PR rate: 53%
Median DOR: 16.6 months
Median PFS: 14.7 months
Cohort C (post-ASCT, post-BV): ORR 68%, median PFS 11.9 months
Adverse events
Overall: grade ≥3 any AE 36%; infusion reactions 12%; treatment discontinuations 5%; no treatment-related deaths in the primary analysis
Immune-mediated (any grade) 44%: rash 22%, hypothyroidism 12%, elevated liver enzymes 8%, pneumonitis 5%
Immune-mediated (any grade) 44%: rash 22%, hypothyroidism 12%, elevated liver enzymes 8%, pneumonitis 5%
Conclusions
Nivolumab achieved a 69% ORR with durable responses (mDOR 16.6 mo) in heavily pretreated R/R cHL after ASCT — including post-BV patients — supporting FDA approval (May 2016) as the first PD-1 inhibitor approved for a hematologic malignancy.
Key Limitations
Single-arm phase II without a comparator, precluding controlled efficacy comparison. CR rate was modest (16%), with most responses being partial. No OS benefit was subsequently demonstrated in the randomized setting (KEYNOTE-204). In the current era, BV+nivolumab (85% ORR, 67% CR) is the preferred salvage combination, and frontline N+AVD (S1826) is now the most impactful use of nivolumab in cHL, making single-agent nivolumab less commonly used.
Clinical Context
CheckMate 205 provided the pivotal evidence for nivolumab's FDA approval in R/R cHL (May 2016). In current practice, monotherapy nivolumab has largely been supplanted by BV+nivolumab (first salvage) and pembrolizumab (KEYNOTE-204). Nivolumab + AVD frontline (S1826) is now the most impactful use of nivolumab in cHL.