TY - JOUR
T1 - 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
AU - Rejeski, Kai
AU - Wang, Yucai
AU - Albanyan, Omar
AU - Munoz, Javier
AU - Sesques, Pierre
AU - Iacoboni, Gloria
AU - Lopez-Corral, Lucia
AU - Ries, Isabelle
AU - Bücklein, Veit L.
AU - Mohty, Razan
AU - Dreyling, Martin
AU - Baluch, Aliyah
AU - Shah, Bijal
AU - Locke, Frederick L.
AU - Hess, Georg
AU - Barba, Pere
AU - Bachy, Emmanuel
AU - Lin, Yi
AU - Subklewe, Marion
AU - Jain, Michael D.
N1 - Publisher Copyright:
© 2023 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.
PY - 2023/11
Y1 - 2023/11
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85168296542&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85168296542&partnerID=8YFLogxK
U2 - 10.1002/ajh.27056
DO - 10.1002/ajh.27056
M3 - Article
C2 - 37584447
AN - SCOPUS:85168296542
SN - 0361-8609
VL - 98
SP - 1699
EP - 1710
JO - American journal of hematology
JF - American journal of hematology
IS - 11
ER -