Background
Phase II, open-label, single-arm study. 39 patients with relapsed or refractory classical Hodgkin lymphoma as second-line therapy (first salvage) intended for autologous hematopoietic cell transplantation (AHCT). Patients had received 1–3 prior lines; prior BV or PD-1 inhibitor allowed (13% had prior BV). The regimen combines PD-1 blockade (pembrolizumab) with standard GVD salvage chemotherapy to maximize pre-transplant CR rates.
Interventions and follow up
Regimen: Pembrolizumab 200 mg IV day 1 + gemcitabine 1000 mg/m² + vinorelbine 20 mg/m² + liposomal doxorubicin 15 mg/m² days 1 and 8, every 21d × 2–4 cycles, in R/R cHL (first salvage prior to autoSCT)
Primary endpoint: CR rate after up to 4 cycles by PET-CT
Median follow up: 13.5 months post-transplant (for transplanted patients)
Primary endpoint: CR rate after up to 4 cycles by PET-CT
Median follow up: 13.5 months post-transplant (for transplanted patients)
Results
CR rate (after up to 4 cycles): 95%
ORR: 100%
Patients proceeding to AHCT: 95% (37/39)
Post-AHCT outcomes: 100% of transplanted patients in remission at median 13.5 months post-transplant
PET-negative pre-AHCT rate: 95%
ORR: 100%
Patients proceeding to AHCT: 95% (37/39)
Post-AHCT outcomes: 100% of transplanted patients in remission at median 13.5 months post-transplant
PET-negative pre-AHCT rate: 95%
Adverse events
Hematologic (grade ≥3): neutropenia 68%, thrombocytopenia 35%, anemia 24%; febrile neutropenia 28%
Immune-mediated: pneumonitis grade ≥3 in 2.6%, elevated liver enzymes 5.1%, rash 5.1%
Other: no treatment-related deaths; all patients mobilized and proceeded to AHCT without major delay
Immune-mediated: pneumonitis grade ≥3 in 2.6%, elevated liver enzymes 5.1%, rash 5.1%
Other: no treatment-related deaths; all patients mobilized and proceeded to AHCT without major delay
Conclusions
Pembrolizumab plus GVD achieved an extraordinary 95% CR rate and 100% ORR in R/R cHL as second-line salvage therapy, with 95% bridging to AHCT and all transplanted patients in remission at median 13.5 months post-transplant. This is one of the highest CR rates reported in R/R cHL salvage, establishing pembro-GVD as a highly effective pre-AHCT regimen.
Key Limitations
Small, single-arm phase II (n=39) with no randomized comparator, so the contribution of pembrolizumab to standard GVD cannot be isolated. Short post-transplant follow-up (median 13.5 months) limits assessment of durable PFS/OS. Population restricted to transplant-eligible patients; results do not extend to transplant-ineligible or heavily PD-1–pretreated disease. PET-based CR may overestimate depth of remission in the context of checkpoint blockade (immune flare).
Clinical Context
Pembro-GVD is a widely adopted preferred second-line salvage option for transplant-eligible R/R cHL, alongside BV+nivolumab, with the goal of PET-negative CR prior to AHCT. Pembrolizumab carries FDA approval in R/R cHL (single-agent, post-prior lines); the GVD combination is used off-label as bridging chemoimmunotherapy. Follow-up work (ASH 2024) is exploring pembrolizumab maintenance to defer transplant in patients achieving CR.