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Rejeski, Kai ORCID logoORCID: https://orcid.org/0000-0003-3905-0251; Wang, Yucai ORCID logoORCID: https://orcid.org/0000-0002-1576-8341; Albanyan, Omar; Munoz, Javier; Sesques, Pierre ORCID logoORCID: https://orcid.org/0000-0001-8264-822X; Iacoboni, Gloria; Lopez‐Corral, Lucia; Ries, Isabelle; Bücklein, Veit L.; Mohty, Razan; Dreyling, Martin; Baluch, Aliyah; Shah, Bijal ORCID logoORCID: https://orcid.org/0000-0003-4328-6021; Locke, Frederick L.; Hess, Georg; Barba, Pere; Bachy, Emmanuel; Lin, Yi; Subklewe, Marion ORCID logoORCID: https://orcid.org/0000-0001-9154-9469 und Jain, Michael D. ORCID logoORCID: https://orcid.org/0000-0002-7789-1257 (2023): The CAR‐HEMATOTOX score identifies patients at high risk for hematological toxicity, infectious complications, and poor treatment outcomes following brexucabtagene autoleucel for relapsed or refractory MCL. In: American Journal of Hematology, Bd. 98, Nr. 11: S. 1699-1710 [PDF, 2MB]

Abstract

CD19-directed CAR T-cell therapy with brexucabtagene autoleucel (brexu-cel) has substantially improved treatment outcomes for patients with relapsed/refractory mantle cell lymphoma (r/r MCL). Prolonged cytopenias and infections represent common and clinically relevant side effects. In this multicenter observational study, we describe cytopenias and infections in 103 r/r MCL patients receiving brexu-cel. Furthermore, we report associations between the baseline CAR-HEMATOTOX (HT) score and toxicity events, non-relapse mortality (NRM), and progression-free/overall survival (PFS/OS). At lymphodepletion, 56 patients were HTlow (score 0–1) while 47 patients were HThigh (score ≥2). The HThigh cohort exhibited prolonged neutropenia (median 14 vs. 6 days, p < .001) and an increased rate of severe infections (30% vs. 5%, p = .001). Overall, 1-year NRM was 10.4%, primarily attributed to infections, and differed by baseline HT score (high vs. low: 17% vs. 4.6%, p = .04). HThigh patients experienced inferior 90-day complete response rate (68% vs. 93%, p = .002), PFS (median 9 months vs. not-reached, p < .0001), and OS (median 26 months vs. not-reached, p < .0001). Multivariable analyses showed that high HT scores were independently associated with severe hematotoxicity, infections, and poor PFS/OS. In conclusion, infections and hematotoxicity are common after brexu-cel and contribute to NRM. The baseline HT score identified patients at increased risk of poor treatment outcomes.

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