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- Title:
The CAR-HEMATOTOX score as a prognostic model of toxicity and response in patients receiving BCMA-directed CAR-T for relapsed/refractory multiple myeloma.
- Document type:
- Journal Article; Research Support, Non-U.S. Gov't
- Author(s):
- Rejeski, Kai; Hansen, Doris K; Bansal, Radhika; Sesques, Pierre; Ailawadhi, Sikander; Logue, Jennifer M; Bräunlein, Eva; Cordas Dos Santos, David M; Freeman, Ciara L; Alsina, Melissa; Theurich, Sebastian; Wang, Yucai; Krackhardt, Angela M; Locke, Frederick L; Bachy, Emmanuel; Jain, Michael D; Lin, Yi; Subklewe, Marion
- Abstract:
- BACKGROUND: BCMA-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. METHODS: Data 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. RESULTS: At 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). CONCLUSIONS: These 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.
- Journal title abbreviation:
- J Hematol Oncol
- Year:
- 2023
- Journal volume:
- 16
- Journal issue:
- 1
- Fulltext / DOI:
- doi:10.1186/s13045-023-01465-x
- Pubmed ID:
- http://view.ncbi.nlm.nih.gov/pubmed/37525244
- TUM Institution:
- 608; Klinik und Poliklinik für Innere Medizin III, Hämatologie und Onkologie (Prof. Bassermann)
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