Session: 331. Pathophysiology of Thrombosis: Poster II
Hematology Disease Topics & Pathways:
multiple myeloma, anticoagulant drugs, Adult, Diseases, Bleeding and Clotting, Non-Biological, Therapies, Non-Hodgkin Lymphoma, Plasma Cell Disorders, Thromboembolism, Lymphoid Malignancies, Study Population, Clinically relevant, Thrombotic Disorders, VTE
Methods: We performed a single-center, retrospective cohort study of all patients who received inpatient CAR-T cells at UCSF Medical Center between January 2018 and May 2020 for R/R NHL or MM as standard-of-care or on a clinical trial. The outcomes of incident VTE and ATE were identified by ICD-10 codes and medical record review. Patient characteristics, pre-existing thrombosis risk factors, laboratory results, medications, and major or clinically relevant non-major bleeding or recurrent thrombotic complications were obtained through chart review. We used descriptive statistics to delineate risk factors, incidence, management and outcomes of thrombotic events.
Results: Ninety-one patients who underwent CAR-T therapy were included in the analysis, 37 with NHL and 54 with MM. For NHL, mean age was 63 (range 38-82), and 41% were women. For MM, mean age was 62 (range 33-77), and 50% were women. Patients with NHL were treated with either investigational or Federal Drug Administration-approved CD19-directed therapies, and patients with MM were treated with a variety of investigational B-cell maturation antigen-directed (BCMA) therapies.
For thrombotic risk factors, 13% of patients with NHL had a history of VTE, 3% had a history of ATE, 27% had a BMI ≥30, 59% had a recent procedure including central venous catheter (CVC) placement, 14% had an intensive care unit (ICU) stay, and 22% had an infectious complication in the 30 days pre- or post-CAR-T. Forty-one percent of patients with NHL had neurotoxicity of any grade, and 59% had CRS of any grade. At 30 days, 57% had a complete response, 41% had a partial response, 3% had stable disease. For MM, 6% of patients had a pre-existing history of VTE, 2% had a history of ATE, 19% had a BMI ≥30, 96% had a recent procedure, 11% had an ICU stay and 19% had an infection. Seventeen percent had neurotoxicity, and 85% had CRS. Thirty-two percent of patients with NHL and 48% with MM received pharmacologic VTE prophylaxis while undergoing CAR-T. For those who did not receive VTE prophylaxis, thrombocytopenia was the reason for holding prophylaxis, which occurred in 51% and 50% of NHL and MM patients, respectively.
In the 60 days post-CAR-T, 4 (11%) patients with NHL were diagnosed with VTE—3 pulmonary embolism (PE) and 1 lower extremity deep vein thrombosis (DVT) associated with a previously placed inferior vena cava filter. Four (7%) patients with MM were diagnosed with VTE—1 PE and 3 upper extremity DVTs associated with CVCs. Five out of these 8 (63%) patients had symptomatic VTE, while the remainder were incidental on PETCT. Mean time from CAR-T infusion to VTE diagnosis was 20 days (range 6-39 days). There were no documented ATEs. Six out of 8 (75%) were treated with therapeutic anticoagulation. Of those who were anticoagulated, 4 patients received direct oral anticoagulants and 2 received low-molecular-weight-heparin. Duration was 3 months in 3 patients, 11 days in 1, 150 days in 1, and indefinitely in 1 with atrial fibrillation. Among all 8 patients with VTE, there were no bleeding events or recurrent thromboses regardless of whether or not they received anticoagulation.
Discussion: In this cohort of patients with R/R NHL or MM who received either CD19- or BCMA-directed therapies, almost 1 in 10 developed VTE in the 60 days post-CAR-T. This occurred in the context of a high prevalence of risk factors for thrombosis and low rates of pharmacologic prophylaxis. Among those who developed VTE, the majority were treated with therapeutic anticoagulation for at least 3 months, without documented bleeding or recurrent VTE. Our findings provide crucial information on a common complication that can inform patients, clinicians and researchers and should be expanded upon in larger, prospective studies to identify optimal preventive and therapeutic strategies.
Disclosures: Fakhri: University of California San Francisco: Current Employment. Andreadis: Jazz Pharmaceuticals: Honoraria; Karyopharm: Honoraria; Incyte: Consultancy; Merck: Research Funding; Gilead/Kite: Consultancy; Novartis: Research Funding; BMS/Celgene/Juno: Honoraria, Research Funding; Genentech: Consultancy, Current equity holder in publicly-traded company. Wong: Janssen: Research Funding; Roche: Research Funding; Sanofi: Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy; Fortis: Research Funding; GSK: Research Funding; Bristol Myers Squibb: Research Funding. Shah: BMS, Janssen, Bluebird Bio, Sutro Biopharma, Teneobio, Poseida, Nektar: Research Funding; GSK, Amgen, Indapta Therapeutics, Sanofi, BMS, CareDx, Kite, Karyopharm: Consultancy.
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