Baseline D-dimer as a predictor of immune checkpoint inhibitor efficacy in cancer.

Abstract

<h4>Background</h4>Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment by enhancing antitumor immunity, yet durable responses are observed in only a fraction of patients. Identifying accessible and reliable biomarkers to predict therapeutic efficacy remains a critical unmet need. D-dimer, a fibrin degradation product reflecting systemic coagulation, has been associated with tumor progression and poor prognosis, but its predictive value in ICI-treated patients remains unclear.<h4>Methods</h4>We conducted a systematic review and meta-analysis of studies evaluating baseline D-dimer in cancer patients receiving ICIs. Eligible studies reported outcomes including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), or disease control rate (DCR). Data extraction and quality assessment were performed independently, and pooled hazard and odds ratios were calculated. Sensitivity and subgroup analyses were conducted to evaluate the stability of findings and potential cutoff-dependent effects.<h4>Results</h4>Ten retrospective studies including 1,217 patients were analyzed. Elevated baseline D-dimer was significantly associated with worse OS (HR = 1.95, 95% CI: 1.62-2.36, <i>p</i> < 0.001) and shorter PFS (HR = 2.03, 95% CI: 1.57-2.63, <i>p</i> < 0.001). Higher D-dimer levels also correlated with lower ORR (OR = 0.42, 95% CI: 0.26-0.68, <i>p</i> < 0.001) and DCR (OR = 0.18, 95% CI: 0.10-0.34, <i>p</i> < 0.001). Sensitivity and subgroup analyses confirmed the robustness and consistency of these associations across tumor types, treatment regimens, and D-dimer thresholds.<h4>Conclusions</h4>Baseline D-dimer is a readily measurable, cost-effective biomarker that predicts inferior outcomes in patients receiving ICIs. Its integration into clinical workflows may aid patient stratification and guide treatment decisions. Prospective multicenter studies are warranted to validate cutoff thresholds and further define its utility in optimizing immunotherapy efficacy.