Red blood cell transfusions impact response rates to immunotherapy in patients with solid malignant tumors

Abstract

Red blood cell (RBC) transfusions have been shown to exert immunosuppressive effects in different diseases. In consequence, RBC transfusions might also negatively influence the response to immunotherapeutic treatment approaches. To address how RBC transfusions impact response rates of antitumor immunotherapy (IT), we conducted a retrolective clinical study of patients with different solid tumors treated with IT (atezolizumab, pembrolizumab, nivolumab and/or ipilimumab). We assessed the number of RBC concentrates received within 30 days before and 60 days after the start of IT. Primary objective was the initial therapy response at first staging, secondary objectives the number of immune related adverse events and infections. 15 of 55 included patients (27.3%) received RBC concentrates. The response rates were 77.5% in the non-transfused (n=40) versus 46.7% in the transfused patient group (n=15) and reached statistical significance (p=0.047). The correlation between therapy response and transfusion was statistically significant (p=0.026) after adjustment for the only identified confounder “line of therapy”. In contrast, transfusion in the interval 30 days before IT showed no significant difference for treatment response (p=0.705). Moreover, no correlation was detected between RBC transfusion and irAE rate (p=0.149) or infection rate (p=0.135). In conclusion, we show for the first time that the administration of RBC transfusions during, but not before initiation of IT treatment, negatively influences the response rates to IT. Our findings suggest a restrictive transfusion management in patients undergoing IT to receive optimal response rates.

Risk factors for blood transfusion and its prognostic implications in curative gastrectomy for gastric cancer

“…The current hypothesis that explains the biological association between blood components and poorer oncological outcomes is that transfusion-related immunomodulation (TRIM) acts as a propagating factor for the TH2 immune response, favoring a pro-tumoral environment through inhibition of interleukin (IL)-2 and stimulation of suppressor T cells, allowing tumor spread and recurrence[ 20 - 22 ]. The recent application of immunotherapy in gastrointestinal tract cancers provided additional data by demonstrating that TRIM could be acting as an opponent and negatively impacting its effectiveness and survival[ 32 ]. Another important topic related to the immune response is the data provided by Lange et al [ 33 ] that showed no difference in using leukocyte depletion in long-term survival, underlining that specific constituents of allogeneic blood may mediate the TRIM effect.…”

Transfusion needs after CAR T-cell therapy for large B-cell lymphoma: predictive factors and outcome (a DESCAR-T study)

“…Transfusions have demonstrated a positive impact on solid organ transplant outcome, a negative one on cancer dissemination and relapse, and on RR to checkpoint inhibitors in solid cancers. 20 , 22 , 43 Transfusion may thus impair CAR T-cell fitness and lead to an increased relapse rate, although this hypothesis needs to be further explored. Finally, prolonged cytopenia can predispose for significant infectious complications, which is the main driver of NRM.…”

A meta-analysis on the risk of infection associated with intravenous iron therapy in cancer-associated anaemia: a double-edged sword?

“…Moreover, the administration of RBC transfusions after the initiation of immunotherapy (IT) treatment, seems to have a detrimental impact on the response rates to immunotherapy. Therefore, recent studies advocate for a conservative approach to transfusion management in patients undergoing immunotherapy [57].…”