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

Research

Jennifer M. Logue¹  Frederick L. Locke¹  Melissa Alsina¹  Michael D. Jain¹  Ciara L. Freeman¹  Doris K. Hansen¹  Sebastian Theurich²  David M. Cordas dos Santos²  Marion Subklewe³  Kai Rejeski³  Sikander Ailawadhi⁴  Yi Lin⁵  Radhika Bansal⁵  Yucai Wang⁵  Angela M. Krackhardt⁶  Emmanuel Bachy⁷  Pierre Sesques⁷  Eva Bräunlein⁸ 

[1] Department of Blood and Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, USA;Department of Medicine III – Hematology/Oncology, LMU University Hospital, LMU Munich, Marchioninistrasse 15, 81377, Munich, Germany;German Cancer Consortium (DKTK), Munich Site, and German Cancer Research Center, Heidelberg, Germany;Department of Medicine III – Hematology/Oncology, LMU University Hospital, LMU Munich, Marchioninistrasse 15, 81377, Munich, Germany;Laboratory for Translational Cancer Immunology, LMU Gene Center, Munich, Germany;German Cancer Consortium (DKTK), Munich Site, and German Cancer Research Center, Heidelberg, Germany;Bavarian Cancer Research Center (BZKF), Munich partner site, Munich, Germany;Division of Hematology and Oncology, Mayo Clinic, Jacksonville, FL, USA;Division of Hematology, Mayo Clinic, Rochester, MN, USA;German Cancer Consortium (DKTK), Munich Site, and German Cancer Research Center, Heidelberg, Germany;Bavarian Cancer Research Center (BZKF), Munich partner site, Munich, Germany;IIIrd Medical Department, Klinikum rechts der Isar and Center for Translational Cancer Research (TranslaTUM), School of Medicine, Technical University of Munich, Munich, Germany;Department of Medicine I, Malteser Hospital St. Franziskus Hospital, Flensburg, Germany;Hospices Civils de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, Pierre-Bénite, France;IIIrd Medical Department, Klinikum rechts der Isar and Center for Translational Cancer Research (TranslaTUM), School of Medicine, Technical University of Munich, Munich, Germany;

关键词: Chimeric antigen receptor;    BCMA CAR-T;    Hematological toxicity;    Cytopenias;    Multiple myeloma;    Infections;   

DOI  :  10.1186/s13045-023-01465-x

 received in 2023-03-05, accepted in 2023-06-09,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundBCMA-directed CAR T-cell therapy (CAR-T) has altered the treatment landscape of relapsed/refractory (r/r) multiple myeloma, but is hampered by unique side effects that can lengthen hospital stays and increase morbidity. Hematological toxicity (e.g. profound and prolonged cytopenias) represents the most common grade ≥ 3 toxicity and can predispose for severe infectious complications. Here, we examined the utility of the CAR-HEMATOTOX (HT) score to predict toxicity and survival outcomes in patients receiving standard-of-care idecabtagene vicleucel and ciltacabtagene autoleucel.MethodsData were retrospectively collected from 113 r/r multiple myeloma patients treated between April 2021 and July 2022 across six international CAR-T centers. The HT score—composed of factors related to hematopoietic reserve and baseline inflammatory state—was determined prior to lymphodepleting chemotherapy.ResultsAt lymphodepletion, 63 patients were HTlow (score 0–1) and 50 patients were HThigh (score ≥ 2). Compared to their HTlow counterparts, HThigh patients displayed prolonged severe neutropenia (median 9 vs. 3 days, p < 0.001), an increased severe infection rate (40% vs. 5%, p < 0.001), and more severe ICANS (grade ≥ 3: 16% vs. 0%, p < 0.001). One-year non-relapse mortality was higher in the HThigh group (13% vs. 2%, p = 0.019) and was predominantly attributable to fatal infections. Response rates according to IMWG criteria were higher in HTlow patients (≥ VGPR: 70% vs. 44%, p = 0.01). Conversely, HThigh patients exhibited inferior progression-free (median 5 vs. 15 months, p < 0.001) and overall survival (median 10.5 months vs. not reached, p < 0.001).ConclusionsThese data highlight the prognostic utility of the CAR-HEMATOTOX score for both toxicity and treatment response in multiple myeloma patients receiving BCMA-directed CAR-T. The score may guide toxicity management (e.g. anti-infective prophylaxis, early G-CSF, stem cell boost) and help to identify suitable CAR-T candidates.

【 授权许可】

CC BY   
© The Author(s) 2023

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