» Articles » PMID: 36455991

Dasatinib for Treatment of CAR T-cell Therapy-related Complications

Overview
Authors
Affiliations
Soon will be listed here.
Abstract

Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are severe, potentially life-threatening side effects of chimeric antigen receptor T-cell (CAR T) therapy caused by the release of cytokines by proliferating and activated CAR T-cells. Current mainstay treatment includes interleukin-1 and interleukin-6 (IL-6) blockade and steroids. The use of steroids is still controversial, since they may have the potential to irreversibly damage CAR T-cells and thus increase the risk of relapse. Therefore, additional treatment options need to be explored. We report the successful treatment of a patient with a grade 3 CRS and grade 4 ICANS refractory to IL-6 blockade and steroids with the tyrosine kinase inhibitor dasatinib. The use of dasatinib for treatment of CAR T-cell therapy-related severe complications warrants further studies.

Citing Articles

Novel strategies to manage CAR-T cell toxicity.

Mulvey A, Trueb L, Coukos G, Arber C Nat Rev Drug Discov. 2025; .

PMID: 39901030 DOI: 10.1038/s41573-024-01100-5.


CAR-T Cells for the Treatment of Central Nervous System Tumours: Known and Emerging Neurotoxicities.

Palazzo L, Pieri V, Berzero G, Filippi M Brain Sci. 2025; 14(12.

PMID: 39766419 PMC: 11727498. DOI: 10.3390/brainsci14121220.


Protocol for production of tonic CAR T cells with dasatinib.

Rosselle L, Leray T, Joaquina S, Caulier B, McCormack E, Gelebart P STAR Protoc. 2024; 6(1):103529.

PMID: 39739533 PMC: 11750262. DOI: 10.1016/j.xpro.2024.103529.


Evolving strategies for addressing CAR T-cell toxicities.

Rankin A, Duncan B, Allen C, Silbert S, Shah N Cancer Metastasis Rev. 2024; 44(1):17.

PMID: 39674824 PMC: 11646216. DOI: 10.1007/s10555-024-10227-1.


Cellular Therapies for Multiple Myeloma: Engineering Hope.

Vera-Cruz S, Jornet Culubret M, Konetzki V, Alb M, Friedel S, Hudecek M Cancers (Basel). 2024; 16(22).

PMID: 39594822 PMC: 11592760. DOI: 10.3390/cancers16223867.


References
1.
Topp M, van Meerten T, Houot R, Minnema M, Bouabdallah K, Lugtenburg P . Earlier corticosteroid use for adverse event management in patients receiving axicabtagene ciloleucel for large B-cell lymphoma. Br J Haematol. 2021; 195(3):388-398. PMC: 9293158. DOI: 10.1111/bjh.17673. View

2.
Weber E, Lynn R, Sotillo E, Lattin J, Xu P, Mackall C . Pharmacologic control of CAR-T cell function using dasatinib. Blood Adv. 2019; 3(5):711-717. PMC: 6418502. DOI: 10.1182/bloodadvances.2018028720. View

3.
Westin J, Sehn L . CAR T cells as a second-line therapy for large B-cell lymphoma: a paradigm shift?. Blood. 2022; 139(18):2737-2746. DOI: 10.1182/blood.2022015789. View

4.
Giavridis T, van der Stegen S, Eyquem J, Hamieh M, Piersigilli A, Sadelain M . CAR T cell-induced cytokine release syndrome is mediated by macrophages and abated by IL-1 blockade. Nat Med. 2018; 24(6):731-738. PMC: 6410714. DOI: 10.1038/s41591-018-0041-7. View

5.
Reagan P, Neelapu S . How I Manage: Pathophysiology and Management of Toxicity of Chimeric Antigen Receptor T-Cell Therapies. J Clin Oncol. 2021; 39(5):456-466. DOI: 10.1200/JCO.20.01616. View