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

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) repr...

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Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10391746/
https://www.ncbi.nlm.nih.gov/pubmed/37525244
http://dx.doi.org/10.1186/s13045-023-01465-x
Descripción
Sumario: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 HT(low) (score 0–1) and 50 patients were HT(high) (score ≥ 2). Compared to their HT(low) counterparts, HT(high) 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 HT(high) group (13% vs. 2%, p = 0.019) and was predominantly attributable to fatal infections. Response rates according to IMWG criteria were higher in HT(low) patients (≥ VGPR: 70% vs. 44%, p = 0.01). Conversely, HT(high) 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13045-023-01465-x.