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Chapter 8 - Confusion

Published online by Cambridge University Press:  24 April 2026

By
Monica K. Wattana ,
Brian Cameron  and
Jonathan Rowland
Edited by
Angela Bray Lindsay  and
Monica Kathleen Wattana
Angela Bray Lindsay
Affiliation:
Virginia Commonwealth University
Monica Kathleen Wattana
Affiliation:
University of Texas, MD Anderson Cancer Center
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Summary

1. Bispecific T-cell engaging Antibody (BsABs) treatments can cause cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) similar to CAR-T, but current data suggests reduced overall severity with grade 3+ events from BsABs being rare.

2. Most CRS/ICANS events associated with BsAB treatment occur within one week after the initial dose or during step-up dosing periods.

3. Grading the severity of the adverse event is critical to appropriate management and disposition. This includes performing an immune effector cell-associated encephalopathy (ICE) score assessment for neurotoxicity cases.

4. The mainstay management for CRS are tocilizumab and steroids, whereas the management for ICANS is high dose steroids since tocilizumab does not cross the blood-brain barrier.

5. Even low grade CRS/ICANS requires discussion with an oncologist given that these treatments are administered in a step-up dose and may or may not be held.

Keywords

bispecific antibody treatmentelranatamabcytokine release syndromeT-cell engagerneurotoxicityinfectiontocilizumabIL-6 inhibitorblinatumomabtebentafuspteclistamabelranatamabtalquetamabmosunetuzumabepcoritamabimmune effector cell-associated neurotoxicity syndrome,

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Chapter
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Oncologic Emergency Medicine
Clinical Cases Illustrating Key Concepts
 , pp. 32 - 40
Publisher: Cambridge University Press
Print publication year: 2026

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References

Further Reading

Daver, N, Neelapu, S, Shpall, E. IEC Therapy Toxicity Assessment and Management. Published online December 13, 2023. Accessed December 11, 2024. www.mdanderson.org/content/dam/mdanderson/documents/for-physicians/algorithms/clinical-management/clin-management-cytokine-release-web-algorithm.pdf.Google Scholar
Goebeler, ME, Bargou, RC. T cell-engaging therapies: BiTEs and beyond. Nat Rev Clin Oncol. 2020;17(7):418–434. doi:10.1038/s41571-020-0347-5CrossRefGoogle ScholarPubMed
Kauer, J, Hörner, S, Osburg, L, et al. Tocilizumab, but not dexamethasone, prevents CRS without affecting antitumor activity of bispecific antibodies. J Immunotherap Cancer. 2020;8(1):e000621. doi:10.1136/jitc-2020-000621CrossRefGoogle Scholar
Lee, DW, Santomasso, BD, Locke, FL, et al. ASTCT consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells. Biol Blood Marrow Transplant. 2019;25(4):625–638. doi:10.1016/j.bbmt.2018.12.758CrossRefGoogle ScholarPubMed
Lim, K, Zhu, X (Sue), Zhou, D, Ren, S, Phipps, A. Clinical pharmacology strategies for bispecific antibody development: learnings from FDA-approved bispecific antibodies in oncology. Clin Pharmacol Ther. 2024;116(2):315–327. doi:10.1002/cpt.3308CrossRefGoogle ScholarPubMed
Markouli, M, Ullah, F, Unlu, S, Omar, N, Lopetegui-Lia, N, Duco, M, et al. Toxicity profile of chimeric antigen receptor T-cell and bispecific antibody therapies in multiple myeloma: pathogenesis, prevention and management. Curr Oncol. 2023;30(7):6330–6352. doi:10.3390/curroncol30070467CrossRefGoogle ScholarPubMed
Research C for DE and. Bispecific Antibodies: An Area of Research and Clinical Applications. FDA. Published online March 12, 2024. Accessed December 12, 2024. www.fda.gov/drugs/spotlight-cder-science/bispecific-antibodies-area-research-and-clinical-applications.Google Scholar
Tian, Z, Liu, M, Zhang, Y, Wang, X. Bispecific T cell engagers: an emerging therapy for management of hematologic malignancies. J Hematol Oncol. 2021;14(1):75. doi:10.1186/s13045-021-01084-4CrossRefGoogle ScholarPubMed
Wattana, MK, Rowland, J, Qdaisat, A, Levavi, H, Anagnostou, T, Sanchez, L, et al. Diagnosis and management of bispecific T cell-engaging antibody toxicity: A primer for emergency physicians. Cancer Treat Rev. 2025;134:102889. doi: 10.1016/j.ctrv.2025.102889. Epub ahead of print. PMID: 39913958.CrossRefGoogle ScholarPubMed

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