Low-dose PD-1 inhibition in relapsed/refractory classic Hodgkin lymphoma: systematic review and meta-analysis.

Introduction: No correlation between the dose, adverse events, and efficacy was detected in clinical trials of anti-PD-1 antibodies across a range of solid and hematological malignancies. Given that dose reduction with potentially comparable clinical efficacy may improve access to treatment, particularly in low-income regions, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of low-dose PD-1 inhibitor monotherapy in relapsed/refractory (r/r) classic Hodgkin lymphoma (cHL).

Materials and methods: Relevant reports were identified through PUBMED, MEDLINE, Cochrane, ScienceDirect databases, and major international conference proceedings, from inception till December 1, 2024. The risk of bias was assessed independently by two authors using the Joanna Briggs's critical appraisal checklist for studies reporting prevalence data. Heterogeneity was assessed using Cochran's Q test, with statistical significance defined as p < 0.05; I² statistic was used to quantify heterogeneity. Random effects models (Der-Simonian method) was used to pool results from primary studies in the presence of significant heterogeneity.

Results: After screening, 13 reports including 148 patients were included in the systematic review. After exclusion of duplicated reports, studies with less than 5 patients, and studies with unextractable data, five studies with a total of 84 patients were included in the meta-analysis. The pooled objective response rate (ORR) with low-dose PD-1 inhibition in r/r cHL, as determined by meta-analysis, was 87% (95% CI, 71.9%-100%), with a corresponding complete response (CR) rate of 53.9% (95% CI, 34.7%-73.1%). The ORR with low-dose nivolumab was 83.8% (95% CI, 64.2%-100%), with a CR rate of 43.3% (95% CI, 29.7%-56.9%). The pooled rate of any-grade adverse events after low-dose PD-1 inhibition was 55.7% (95% CI, 36.1%-75.3%), with a grade 3-4 adverse event rate of 7.5% (95% CI, 1.7%-13.3%).

Conclusions: This systematic review and meta-analysis demonstrated the high efficacy and acceptable toxicity of low-dose PD-1 inhibition in r/r cHL.