Background Transfusions of packed red blood cells (PRBC) have been postulated to be immunosuppressive, an effect known as transfusion-related immunomodulation (TRIM). TRIM is thought to be a result of the immunosuppressive and pro inflammatory effects of residual leukocytes, apoptotic cells, inflammatory mediators, micro particles and free hemoglobin1 Prior studies have shown a negative association between perioperative PRBC transfusions and overall mortality in multiple malignancies.2–13 To date there are no studies addressing the impact of transfusions on survival in patients undergoing treatment with checkpoint inhibitor (CPI) immunotherapy. We conducted a retrospective study to investigate the clinical outcomes associated with PRBC transfusions in patients with non-small cell lung cancer (NSCLC), urothelial carcinoma (UC) and renal cell carcinoma (RCC) who received immunotherapy for advanced/metastatic disease.
Methods From January 2010 - June 2019, patients at Fox Chase Cancer Center who received a PRBC transfusion within 120 days of treatment with a CPI and with advanced NSCLC, UC and RCC were included. Patient demographics including age, sex, ethnicity, race, tobacco use and ECOG performance status (PS) were abstracted. We also assessed previous chemotherapy, radiation and targeted therapy utilization among all patients. The primary endpoints were progression free survival (PFS) and overall survival (OS) in those who have and have not received PRBCs. We then evaluated PFS and OS via a cox proportional hazards model that was adjusted for cancer type, age, PS, previous therapies and tobacco use.
Results 304 patients including 272 NSCLC, 24 UC and 8 RCC subjects were evaluated. 54 patients underwent a minimum of one PRBC transfusion during the pre-specified time period. Both median PFS (8.2 months versus 3.9) and overall survival (26.1 months versus 13.8) were shorter in patients who underwent transfusion. After multivariable adjustment, the negative associations between transfusion and PFS (HR: 1.53, p=0.03) and overall survival (HR: 1.40, p=0.09) were preserved (figure 1–2). A sub-analysis of the NSCLC patients was conducted and shorter PFS (HR:1.58, p=0.03) and overall survival (HR:1.56, P=0.03) were again seen in the transfusion cohort (figure 3–4).
Conclusions PRBC transfusions led to an inferior PFS and OS in advanced cancer patients receiving checkpoint inhibitors even after adjustments for multiple prognostic variables. These results suggest a possible attenuation of the effectiveness of immunotherapy as a result of the immunosuppressive effects of PRBC transfusions. The findings require prospective and mechanistic confirmation as inherent bias may exist in this retrospective analysis.
Ethics Approval This study was approved the institutional review board at Fox Chase Cancer Center, approval number 19-9006.
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