The CAR-HEMATOTOX score as a prognostic model of toxicity and response in patients receiving BCMA-directed CAR-T for relapsed/refractory multiple myeloma

被引:43
|
作者
Rejeski, Kai [1 ,2 ,3 ,4 ,5 ]
Hansen, Doris K. [6 ]
Bansal, Radhika [7 ]
Sesques, Pierre [8 ]
Ailawadhi, Sikander [9 ]
Logue, Jennifer M. [6 ]
Braeunlein, Eva [10 ,11 ]
dos Santos, David M. Cordas M.
Freeman, Ciara L. [6 ]
Alsina, Melissa [6 ]
Theurich, Sebastian [1 ,3 ,4 ]
Wang, Yucai [7 ]
Krackhardt, Angela M. [3 ,4 ,5 ,10 ,11 ,12 ]
Locke, Frederick L. [6 ]
Bachy, Emmanuel [8 ]
Jain, Michael D. [6 ]
Lin, Yi [7 ]
Subklewe, Marion [1 ,2 ,3 ,4 ,5 ]
机构
[1] Ludwig Maximilians Univ Munchen, LMU Univ Hosp, Dept Med Hematol Oncol 3, Marchioninistr 15, D-81377 Munich, Germany
[2] LMU Gene Ctr, Lab Translat Canc Immunol, Munich, Germany
[3] German Canc Consortium DKTK, Munich Site, Heidelberg, Germany
[4] German Canc Res Ctr, Heidelberg, Germany
[5] Bavarian Canc Res Ctr BZKF, Munich Partner Site, Munich, Germany
[6] H Lee Moffitt Canc Ctr & Res Inst, Dept Blood & Marrow Transplant & Cellular Immunoth, Tampa, FL USA
[7] Mayo Clin, Div Hematol, Rochester, MN USA
[8] Univ Claude Bernard Lyon 1, Hosp Civils Lyon, INSERM 1052, Pierre Benite, France
[9] Mayo Clin, Div Hematol & Oncol, Jacksonville, FL USA
[10] Tech Univ Munich, Klinikum Rechts Isar, Sch Med, Med Dept 3, Munich, Germany
[11] Tech Univ Munich, Ctr Translat Canc Res TranslaTUM, Sch Med, Munich, Germany
[12] Malteser Hosp St Franziskus Hosp, Dept Med I, Flensburg, Germany
关键词
Chimeric antigen receptor; BCMA CAR-T; Hematological toxicity; Cytopenias; Multiple myeloma; Infections; CYTOKINE RELEASE SYNDROME; CELL THERAPY; BONE-MARROW; INFECTIOUS COMPLICATIONS; ANTIGEN; OUTCOMES;
D O I
10.1186/s13045-023-01465-x
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
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 & GE; 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 & GE; 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 & GE; 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 (& GE; 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.
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页数:13
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