Neue Medikamente, neue Nebenwirkungen? – Spezielle Nebenwirkungen der CAR-T-Zelltherapie

Chimäre Antigenrezeptor (CAR)-T-Zell-Therapien gewinnen in der Behandlung von Krebserkrankungen zunehmend an Bedeutung. Diese können spezifische Nebenwirkungen hervorrufen, welche eine gezielte Überwachung, rasche Diagnostik und Therapie sowie eine strukturierte Nachsorge erforderlich machen. Dieser Artikel beleuchtet spezifische Nebenwirkungen aktuell in klinischem Einsatz befindlicher CAR-T-Zell-Therapien bei hämatologischen Erkrankungen.

Schlüsselwörter

CAR-T-Zelltherapie - Nebenwirkungen - Cytokine-Release-Syndrome - Neurotoxizität - Hämatotoxizität

• Literatur

• 1 Labanieh L, Mackall CL. CAR immune cells: design principles, resistance and the next generation. Nature 2023; 614: 635-648
• 2 San-Miguel J, Dhakal B, Yong K. et al. Cilta-cel or Standard Care in Lenalidomide-Refractory Multiple Myeloma. New England Journal of Medicine 2023; 389: 335-347
• 3 Brudno JN, Kochenderfer JN. Current understanding and management of CAR T cell-associated toxicities. Nature Reviews Clinical Oncology 2024; 21: 501-521
• 4 Berdeja JG, Madduri D, Usmani SZ. et al. Ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy in patients with relapsed or refractory multiple myeloma (CARTITUDE-1): a phase 1b/2 open-label study. Lancet 2021; 398: 314-324
• 5 Maude SL, Laetsch TW, Buechner J. et al. Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia. New England Journal of Medicine 2018; 378: 439-448
• 6 Schuster SJ, Bishop MR, Tam CS. et al. Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma. N Engl J Med 2019; 380: 45-56
• 7 Pennisi M, Sanchez-Escamilla M, Flynn JR. et al. Modified EASIX predicts severe cytokine release syndrome and neurotoxicity after chimeric antigen receptor T cells. Blood Advances 2021; 5: 3397-3406
• 8 Frenking JH, Zhou X, Wagner V. et al. EASIX-guided risk stratification for complications and outcome after CAR T-cell therapy with ide-cel in relapsed/refractory multiple myeloma. Journal for ImmunoTherapy of Cancer 2024; 12: e009220
• 9 Le RQ, Li L, Yuan W. et al. FDA Approval Summary: Tocilizumab for Treatment of Chimeric Antigen Receptor T Cell-Induced Severe or Life-Threatening Cytokine Release Syndrome. The Oncologist 2018; 23: 943-947
• 10 Cordas dos Santos DM, Tix T, Shouval R. et al. A systematic review and meta-analysis of nonrelapse mortality after CAR T cell therapy. Nature Medicine 2024; 30: 2667-2678
• 11 Lee DW, Santomasso BD, Locke FL. et al. ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells. Biology of Blood and Marrow Transplantation 2019; 25: 625-638
• 12 Sesques P, Kirkwood AA, Kwon M. et al. Novel prognostic scoring systems for severe CRS and ICANS after anti-CD19 CAR T cells in large B-cell lymphoma. J Hematol Oncol 2024; 17: 61
• 13 Shumilov E, Boyadzhiev H, Mazzeo P. et al. CAR-T Cell Therapy Shows Similar Efficacy and Toxicity in Patients With DLBCL Regardless of CNS Involvement. HemaSphere 2023; 7: e984
• 14 Herr MM, Chen GL, Ross M. et al. Identification of neurotoxicity after chimeric antigen receptor (CAR) T cell infusion without deterioration in the immune effector cell-associated encephalopathy (ICE) score. Biology of Blood and Marrow Transplantation 2020; 26: e271-e274
• 15 Rejeski K, Wang Y, Hansen DK. et al. Applying the EHA/EBMT grading for ICAHT after CAR-T: comparative incidence and association with infections and mortality. Blood Advances 2024; 8: 1857-1868
• 16 Rejeski K, Jain MD, Shah NN. et al. Immune effector cell-associated haematotoxicity after CAR T-cell therapy: from mechanism to management. The Lancet Haematology 2024; 11: e459-e470
• 17 Rejeski K, Hansen DK, Bansal R. et al. The CAR-HEMATOTOX score as a prognostic model of toxicity and response in patients receiving BCMA-directed CAR-T for relapsed/refractory multiple myeloma. Journal of hematology & oncology 2023; 16: 88
• 18 Bhutani M. Boosting CAR T cytopenias with backup autologous stem cells. Transplantation and Cellular Therapy, Official Publication of the American Society for Transplantation and Cellular Therapy 2023; 29: 535-536
• 19 Hines MR, Knight TE, McNerney KO. et al. Immune Effector Cell-Associated Hemophagocytic Lymphohistiocytosis-Like Syndrome. Transplantation and Cellular Therapy, Official Publication of the American Society for Transplantation and Cellular Therapy 2023; 29: 438.e431-438.e416
• 20 Tix T, Alhomoud M, Shouval R. et al. Second Primary Malignancies after CAR T-Cell Therapy: A Systematic Review and Meta-analysis of 5,517 Lymphoma and Myeloma Patients. Clinical Cancer Research 2024; 30: 4690-4700