Bleeding and thrombosis associated with CAR-T therapy

This article is from the NEJM Journal Watch Adverse Events Associated with CAR-T Therapy Review of Adverse Events Associated with CAR-T Therapy by Brady Stein, MD, MHS Bleeding or thrombosis occurs in some patients, especially those with older patients.
Patients with high-grade ICANS
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Chimeric antigen receptor T-cell (CAR-T) therapy has had a profound impact on patients with chemotherapy-refractory B-cell lymphoma or acute B-lymphocytic leukemia (B-ALL) and appears to be manifested in multiple myeloma out of prospects
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This therapy is currently known to be associated with certain toxicities, including cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome (ICANS)
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However, we do not yet know whether CAR-T therapy increases the risk of bleeding or thrombosis
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To answer this question, we conducted a retrospective single-center analysis of 111 patients with relapsed or refractory diffuse large B-cell lymphoma and 16 patients with B-ALL, all of whom received CAR-T therapy
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Of these, 89 patients received axi-cel and 38 received a bispecific CD 19/22 CAR construct
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Important findings were as follows: 12 patients (9.
4%) had a protocol-defined bleeding event within 1 month of receiving CAR-T therapy; 7 events occurred after patient discharge
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Hemorrhagic events included 6 cases of gross hematuria, 2 cases of soft tissue hemorrhage, 2 cases of subdural hematoma, 1 case of gastrointestinal bleeding and 1 case of hemoptysis
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In multivariate analysis, only baseline thrombocytopenia was associated with bleeding events
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High-grade ICANS is associated with bleeding and coagulation abnormalities, including prolonged prothrombin time, decreased fibrinogen, and increased d-dimer
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Thrombotic events occurred in 8 patients (6.
3%) within 3 months of treatment, including 5 cases of deep vein thrombosis, 2 cases of splanchnic vein thrombosis, and 1 case of stroke
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High-grade ICANS is associated with thrombosis
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Anticoagulation therapy was not associated with bleeding events
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Commentary This article describes a relatively unknown toxicity of CAR-T therapy and identifies patients requiring close follow-up, especially those with baseline thrombocytopenia or higher-grade ICANS
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Given the relatively low incidence of thrombosis, it is difficult to identify patient-specific characteristics associated with thrombosis risk other than ICANS
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The results of this study help us to further understand the adverse events associated with CAR-T therapy, and also show that anticoagulant therapy is well tolerated in this study population, which is reassuring to some extent
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Reviewed article Johnsrud A et al.
Incidence and risk factors associated with bleeding and thrombosis following chimeric antigen receptor T-cell therapy.
Blood Adv 2021 Nov 9; 5:4465.
(https://doi.
org/10.
1182/bloodadvances.
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