Erythrocyte Transfusion as an Independent Predictor of Survival but Not Immune-Related Toxicity in Nivolumab-Treated Metastatic NSCLC: A Multicenter Cohort

Background and Objectives: Transfusion-related immunomodulation (TRIM) is a recognized immunosuppressive phenomenon whose interaction with immune checkpoint blockade remains poorly defined. We evaluated the impact of erythrocyte suspension transfusion on survival and immune-related toxicity in patients with metastatic non-small cell lung cancer (NSCLC) treated with nivolumab. Materials and Methods: This retrospective, multicenter study included 253 patients with metastatic NSCLC treated with nivolumab across five centers between April 2018 and March 2025. Patients who received a transfusion within three months before or during nivolumab therapy were compared with non-transfused patients. Survival was assessed using Kaplan–Meier and Cox regression analyses. Results: Forty-two patients (16.6%) received transfusion. Transfused patients had significantly shorter progression-free survival (PFS) (median 3.6 vs. 9.3 months; HR = 2.28, 95% CI 1.47–3.56, p < 0.001) and overall survival (OS) (median 5.8 vs. 16.3 months; HR = 2.76, 95% CI 1.86–4.11, p < 0.001). In multivariable analysis, transfusion was an independent predictor of both shorter PFS (HR = 2.288, 95% CI 1.470–3.561, p < 0.001) and shorter OS (HR = 2.351, 95% CI 1.565–3.533, p < 0.001), independent of transfusion volume. No statistically significant association was detected between transfusion status and the incidence of nivolumab-related toxicity (p = 0.585), although this analysis was likely underpowered, whereas nivolumab-related toxicity was an independent favorable prognostic factor. Conclusions: Erythrocyte transfusion independently predicted poorer survival but not immune-related toxicity in nivolumab-treated metastatic NSCLC, supporting more judicious transfusion practices during immunotherapy.