Incidence and risk factors for venous thromboembolism after CAR T-cell therapy: A systematic review and meta-analysis.

Abstract

e24085 Background: Chimeric antigen receptor (CAR) T-cell therapy has revolutionized hematologic cancer treatment; however, the incidence of venous thromboembolism (VTE) after infusion remains understudied. As indications for CAR T expand into solid tumors and more oncologists oversee care, recognizing VTE risk is crucial to mitigate morbidity and mortality in this growing population. Methods: This systematic review and meta-analysis was pre-registered on PROSPERO. Following PRISMA guidelines, we searched Medline, Embase, and CENTRAL (Cochrane Central Register of Controlled Trials) through January 1, 2024, for studies enrolling >20 adults treated with any FDA-approved CAR T-cell product (axicabtagene ciloleucel, tisagenlecleucel, brexucabtagene autoleucel, lisocabtagene maraleucel, idecabtagene vicleucel, or ciltacabtagene autoleucel) that reported VTE events (pulmonary embolism, deep vein thrombosis, cerebral vein thrombosis, hepatic vein thrombosis, splenic vein thrombosis, or portal vein thrombosis) post infusion. Studies not reporting VTE were excluded. All statistical analyses were performed in R software (version R version 4.4.0) using the DerSimonian-Laird random-effects model. Heterogeneity was assessed using the Cochrane Q-statistic and quantified via I 2 ; I 2 >50% indicated substantial heterogeneity. Publication bias was evaluated with funnel plots, Egger’s test, and trim-and-fill method. P<0.05 indicated significance in all analyses. Results: From 7,579 records, 24 studies (2,945 patients) met inclusion. The overall VTE proportion post-CAR T infusion was 6.16% (95% CI 4.58–8.24%), and 4.64% (95% CI 3.41–6.29%) were ≥ grade 3 based on the Common Terminology Criteria for Adverse Events (CTCAE). Most events occurred within 50 days post-infusion. In two studies with control arms, VTE risk did not differ between CAR T recipients and standard-of-care (risk ratio [RR]=0.47, 95% CI 0.08–2.70; P=0.39). Grade >2 cytokine release syndrome (CRS; RR=4.12, 95% CI 2.94–11.63), immune effector cell-associated neurotoxicity syndrome (ICANS; RR=3.43, 95% CI 1.55–11.61), and Eastern Cooperative Oncology Group (ECOG) performance status >1 (RR=4.43, 95% CI 1.91–10.29) significantly increased VTE risk. No major bleeding was observed among patients on therapeutic anticoagulation. Publication bias was detected (Egger’s test, P<0.001), and trim-and-fill analysis yielded an adjusted proportion of 7.82% (95% CI 5.83–10.43%). Conclusions: Approximately 6–8% of patients develop VTE after CAR T-cell therapy, with higher risk among those who have grade >2 CRS, ICANS, or ECOG >1. Given CAR T’s expanding role, these findings underscore the need for vigilant VTE assessment and management. Future investigations should evaluate prophylactic anticoagulation strategies to reduce VTE risk in this setting.