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Autologous stem cell boost improves persistent immune effector cell associated hematotoxicity following BCMA directed chimeric antigen receptor T (CAR T) cell therapy in multiple myeloma

Abstract

Persistent Immune Effector Cell Associated Hematotoxicity (ICAHT) is a significant side effect of BCMA CAR T-Cell therapy in patients with relapsed multiple myeloma (MM). The use of stem cell boosts in ICAHT has been described, however studies have been limited by small patient numbers and short follow up. Herein, we report on our multi-institutional experience of ICAHT, defined by an absolute neutrophil count (ANC) of ≤ 1000, thrombocytopenia with a platelet count ≤ 50,000 or/and anemia as hemoglobin (hgb) ≤9 g/dL, in patients who received BCMA CAR T therapy, and the effects of subsequent stem cell boost on hematopoietic reconstitution and clinical outcome. In this study, ICAHT was observed in 60% (n = 61/101) of patients at D + 21, and risk factors for its development included history of a prior ASCT, higher number of prior lines of therapy, a decreased platelet count prior to lymphodepletion and history of ICANS. 28% of patients with ICAHT received a stem cell boost at a median of 116 days due to profound and prolonged cytopenias often requiring ongoing transfusion support. Stem cell boost significantly improved cytopenias at 3 and 6 months follow up without any adverse effects on PFS and OS, underscoring the safety of this procedure.

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Acknowledgements

Advancing a Healthier Wisconsin Endowment-CTSI KL2 award (M.M). List of where and when the study has been presented in part elsewhere, if applicable: This work will be partly presented as an oral abstract at the 65th American Society of Hematology Annual Meeting and Exposition, Dec 9–12, 2023, San Diego, California.

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Contributions

Conception and design: MM MD, MS; CS MD. Provision of study materials or patients: MM MD, MS; JE RN; CS PA; AG APRN; SAH MD MS; SVR MD; ST MD; MZ MD; NS MD; FvR MD Ph.D.; BD MD, MS; MH MD; AD’S MD, MS; CS MD. Collection and assembly of data: MM MD, MS; JE RN; TPq, MD; RB MD; AJ BA; VB MD; EA BS; CS MD. Data analysis and interpretation: AS Ph. D, LER Sc, MM MD, MS; CS MD. Manuscript writing: MM MD, MS; CS MD. Final approval of manuscript: All author. Non-Author Contributions to Data Collection, Analysis, Or Writing/Editing Assistance: Not Applicable.

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Correspondence to Meera Mohan.

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Mohan, M., Szabo, A., Patwari, A. et al. Autologous stem cell boost improves persistent immune effector cell associated hematotoxicity following BCMA directed chimeric antigen receptor T (CAR T) cell therapy in multiple myeloma. Bone Marrow Transplant (2024). https://doi.org/10.1038/s41409-024-02233-2

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