Venous thromboembolism among cancer patients receiving chimeric antigen receptor-T cell therapy.

Abstract

11179 Background: Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment of advanced cancers. Although, immune side effects (ICANS or CRS) of CARTs are well recognized, and have standardized guidelines for their management, venous thromboembolism risk (VTE) is scant. As the usage of CART is anticipated to increase in upcoming years, it is of utmost importance to characterize factors associated with increased VTE risk. Methods: Using the TriNetX database, we conducted a retrospective analysis to evaluate incidence and risk factors of VTE post CART. Eligibility included administration of any one of the six CAR-T therapies (Tisagenlecleucel, Axicabtagene (Axi-cel), Brexucabtagene, Lisocabtagene, Idecabtagene and Ciltacabtagene) at age ≥18y. VTE were identified using ICD codes for either upper extremity thrombosis or lower extremity deep vein thrombosis, pulmonary embolism, cerebral sinus thrombosis, splenic vein thrombosis or portal vein thrombosis. We further compared these patients to CART recipients without these VTE. Univariate analysis using TriNetX built-in feature (outcome comparison) was performed to compare factors associated with VTE including demographics, comorbidities, cancer type, and treatment. Results: We analyzed data from 133 million+ patients from over 103 health care organizations. There were 2076 adult CAR-T recipients. Axi-cel was the most frequently used CART type. 347/2076 (16.7%) patients developed a VTE after CAR-T, with 10% (210/2076) developing it within three months. CART with VTE cohort had a mean age of 64 years, predominantly males (201/347, 58%) and Caucasian (264/347, 76%). In univariate analysis, when compared to CART without VTE cohort (N =1033), we identified factors significantly associated with VTE. This included history of nicotine dependence (35% vs 24%, P <0.0001), primary hypertension (23% vs 19%, P <0.0001), obesity (25% vs 17%, P =0.0007), hyperlipidemia (45% vs 30%, P <0.0001), h/o radiation (35% vs 18%, P <0.0001), and use of Axi-cel (42% vs 7%, P <0.0001). The use of glucocorticoids (95% vs 77%, P< 0.0001), alkylating agents (91% vs 71%, P< 0.0001) or lenalidomide (18% vs 11%, P =0.0006) were significantly associated with VTE. The underlying cancer type also affected the risk of VTE, having significant association with diffuse large B-cell lymphoma (64% vs 50%, P< 0.0001), mantle cell lymphoma (11% vs 7%, P= 0.0198), and small cell B-cell lymphoma (8% vs 4%, P= 0.0018). Conclusions: There is 10% incidence of VTE within three months of CAR-T therapy. Particularly, VTE incidence is higher with Axi-cel, and DLBCL diagnosis. Patients with high –risk associations may benefit from thromboprophylaxis regimens, particularly during initial three months of CAR-T therapy. Prospective research is warranted to further validate such risk factors and develop evidence-based thromboprophylaxis guidelines for CART recipients.