Background
Phase II, open-label, single-arm, 3-cohort study (KEYNOTE-087). 210 patients with relapsed or refractory classical Hodgkin lymphoma: Cohort 1 (post-ASCT + post-BV failure, n=69), Cohort 2 (chemotherapy-sensitive, ASCT-ineligible + post-BV, n=81), Cohort 3 (post-ASCT, BV-naive, n=60). Pembrolizumab administered at standard fixed dosing.
Interventions and follow up
Regimen: Pembrolizumab 200 mg IV every 3 weeks for up to 2 years in R/R classical Hodgkin lymphoma (three cohorts: post-autoSCT+BV; chemo-refractory non-transplant candidates; post-autoSCT without BV)
Primary endpoint: ORR by blinded independent central review per irRECIST
Median follow up: 5 years (Armand et al, Blood 2023)
Primary endpoint: ORR by blinded independent central review per irRECIST
Median follow up: 5 years (Armand et al, Blood 2023)
Results
ORR: 71.4% (95% CI 64.8–77.4)
CR rate: 27.6%
PR rate: 43.8%
Median PFS: 13.7 months
5-yr PFS rate: 25.7%
Durability: ~1/4 of responders maintained response ≥4 years at 5-yr follow-up
CR rate: 27.6%
PR rate: 43.8%
Median PFS: 13.7 months
5-yr PFS rate: 25.7%
Durability: ~1/4 of responders maintained response ≥4 years at 5-yr follow-up
Adverse events
Overall: grade ≥3 treatment-related AEs 13.2%; treatment-related discontinuations 9.5%; no treatment-related deaths
Immune-mediated (any grade) 25%: hypothyroidism 9%, pneumonitis 5.2%, colitis 2.4%; most immune AEs resolved with standard management (steroids, hormone replacement)
Immune-mediated (any grade) 25%: hypothyroidism 9%, pneumonitis 5.2%, colitis 2.4%; most immune AEs resolved with standard management (steroids, hormone replacement)
Conclusions
Pembrolizumab achieved a 71.4% ORR with durable responses in approximately one-quarter of patients at 5 years, supporting its role as an active and manageable therapy in R/R cHL. FDA approved March 14, 2017, for R/R cHL after ≥3 prior lines of therapy.
Key Limitations
Single-arm phase II without a comparator, limiting controlled efficacy assessment. The 5-yr PFS of 25.7% indicates that the majority of patients eventually progress on monotherapy despite a high initial ORR. The pooled three-cohort design mixes heterogeneous populations (post-ASCT, ASCT-ineligible, BV-naive), limiting subgroup-specific inference. Subsequent randomized data (KEYNOTE-204) and combination regimens (BV+nivolumab, pembro-GVD) have refined the positioning of single-agent pembrolizumab in R/R cHL.
Clinical Context
KEYNOTE-087 supported FDA approval of pembrolizumab (March 2017) for R/R cHL after ≥3 prior lines and refractory to or relapsed after ASCT. The subsequent randomized KEYNOTE-204 established pembrolizumab superior to BV monotherapy, and ESMO/ASCO guidance positions PD-1 blockade as a preferred R/R option. At major centers, combination salvage (BV+nivolumab, pembro-GVD) is now favored for transplant-eligible patients, with single-agent pembrolizumab reserved for those ineligible for intensive salvage.