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Adverse Events Associated with CAR-T Therapy
Chimeric antigen receptor T-cell (CAR-T) therapy has had a profound impact on patients with chemotherapy-refractory B-cell lymphoma or B-acute lymphoblastic leukemia (B-ALL), and it appears promising in patients with multiple myeloma. Certain toxicities are known to be associated with this treatment, including cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome (ICANS). However, whether CAR-T therapy increases risk for bleeding or thrombotic consequences is unknown.
To address this issue, investigators 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 were treated with CAR-T therapy. Of these, 89 received axicabtagene ciloleucil (axi-cel), and 38 received a bispecific CD 19/22 CAR construct.
Key findings were as follows:
- Twelve patients (9.4%) experienced a protocol-defined bleeding event within the first month following CAR-T treatment; 7 events occurred after hospital discharge.
- Bleeding events included gross hematuria in 6 patients, soft-tissue bleeding in 2, subdural hematoma in 2, gastrointestinal hemorrhage in 1, and hemoptysis in 1.
- Only baseline thrombocytopenia was associated with bleeding events in a multivariate analysis.
- High-grade ICANS was associated with bleeding and coagulation abnormalities, including prolonged prothrombin time, decreased fibrinogen, and increased d-dimer.
- Eight patients (6.3%) experienced thrombotic events within 3 months following treatment; of these, 5 had deep venous thrombosis, 2 had splanchnic vein thrombosis, and 1 had a stroke. High-grade ICANS was associated with thrombosis.
- Anticoagulation was not associated with bleeding events.
Comment
This report describes a lesser-known toxicity of CAR-T therapy and identifies patients in need of close follow-up, especially those with baseline thrombocytopenia or higher-grade ICANS. Given the relatively low rate of thrombosis, it was difficult to define specific patient characteristics, apart from ICANS, that were associated with thrombosis risk. This study provides some reassurance about the tolerability of anticoagulation in the study population and adds to our understanding of adverse events associated with this impactful immunotherapy.
Citation(s)
Author:
Johnsrud A et al.
Title:
Incidence and risk factors associated with bleeding and thrombosis following chimeric antigen receptor T-cell therapy.
Source:
Blood Adv
2021
Nov
9; [e-pub].
(Abstract/FREE Full Text)
Empfohlen von
Brady Stein, MD, MHS