Background
Phase II, open-label, single-arm study. 53 patients with R/R PMBCL after ≥2 prior lines (including brentuximab vedotin-containing regimens or autologous transplant). PMBCL shares molecular features with classical Hodgkin lymphoma, including PD-L1/PD-L2 upregulation via 9p24.1 amplification, providing biological rationale for PD-1 blockade.
Interventions and follow up
Regimen: Pembrolizumab 200 mg IV every 3 weeks for up to 2 years in R/R primary mediastinal B-cell lymphoma
Primary endpoint: Overall response rate (independent central review)
Median follow-up: 29.1 months (updated analysis)
Primary endpoint: Overall response rate (independent central review)
Median follow-up: 29.1 months (updated analysis)
Results
ORR (primary): 45.3% (95% CI 31.6–59.6%)
CR rate: 17.0%
Median DoR: Not reached (range 1.1+ to 29.2+ months)
12-month PFS: 38.9%
Median OS: Not reached (12-month OS 58.0%)
CR rate: 17.0%
Median DoR: Not reached (range 1.1+ to 29.2+ months)
12-month PFS: 38.9%
Median OS: Not reached (12-month OS 58.0%)
Adverse events
Immune-mediated: Grade ≥3 immune-mediated AEs 11.3%; pneumonitis any grade 15.1% (grade ≥3 3.8%); hypothyroidism 17.0%.
Other: Infusion reactions 3.8%; one treatment-related death (myocarditis); treatment discontinuation due to AEs 5.7%.
Other: Infusion reactions 3.8%; one treatment-related death (myocarditis); treatment discontinuation due to AEs 5.7%.
Conclusions
Pembrolizumab demonstrated a 45.3% ORR with durable responses in heavily pretreated R/R PMBCL, establishing PD-1 blockade as an effective and tolerable strategy in this 9p24.1-amplified tumor. Responses in CR patients appear durable.
Key Limitations
Single-arm phase II design with small sample (n=53) and no comparator. ORR of 45% leaves the majority without response, and the 17% CR rate is modest. Median PFS/OS not formally reported beyond landmark estimates. Sequencing relative to CAR-T and the durability of partial responses remain undefined.
Clinical Context
The FDA granted accelerated approval to pembrolizumab for R/R PMBCL after ≥2 prior lines (2018), supported by KEYNOTE-13 and KEYNOTE-170. KEYNOTE-170 provides the mature efficacy and durability data. ASCO/ESMO recognize PD-1 blockade as an option in relapsed PMBCL, with CD19 CAR-T also active in this disease; optimal sequencing is unsettled.