Development and validation of the post-CAR prognostic index for large B-cell lymphoma patients after CAR-T progression in third or later line treatment

Development and validation of the post-CAR prognostic index for large B-cell lymphoma patients after CAR-T progression in third or later line treatment

Abstract Chimeric antigen receptor (CAR) T-cell therapy fails to achieve durable responses in over 60% of relapsed/refractory (R/R) large B-cell lymphoma (LBCL) patients in the third or later line setting. After CAR-T failure, survival outcomes are heterogeneous and a prognostic model in this patien...

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Main Authors: Gloria Iacoboni, Víctor Navarro, Pierre Sesques, Kai Rejeski, Mariana Bastos-Oreiro, Fabio Serpenti, Ana Africa Martin Lopez, Josu Iraola-Truchuelo, Javier Delgado, Ariadna Perez, Manuel Guerreiro, Ana Carolina Caballero, Nuria Martinez-Cibrian, Hugo Luzardo Henriquez, Jose Maria Sanchez Pina, Juan-Manuel Sancho, Hervé Ghesquieres, Alberto Mussetti, Lucia Lopez Corral, Rafael Hernani, Juan Luis Reguera, Anna Sureda, Francesc Bosch, Alejandro Martin Garcia-Sancho, Mi Kwon, Marion Subklewe, Andrea Kuhnl, Emmanuel Bachy, Pere Barba, Guillermo Villacampa, Pau Abrisqueta
Format: Article
Language:English
Published: BMC 2024-10-01
Series:Journal of Hematology & Oncology
Subjects:
CAR-T
Large B-cell lymphoma
Overall survival
Score
Disease progression
Online Access:https://doi.org/10.1186/s13045-024-01608-8
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Summary:Abstract Chimeric antigen receptor (CAR) T-cell therapy fails to achieve durable responses in over 60% of relapsed/refractory (R/R) large B-cell lymphoma (LBCL) patients in the third or later line setting. After CAR-T failure, survival outcomes are heterogeneous and a prognostic model in this patient population is lacking. A training cohort of 216 patients with progressive disease (PD) after CAR-T from 12 Spanish centers was used to develop the Post-CAR Prognostic Index (PC-PI); primary endpoint was overall survival (OS) from CAR-T progression. Validation was performed in an external cohort from three different European centers (n = 204). The prognostic score incorporated five variables, assessed at time of PD to CAR-T: ECOG (> 0), hemoglobin (< 10 g/dL), LDH (≥ 2xULN), number of extranodal sites (> 1) and time from CAR-T to PD (< 4 months). Patients were classified in four risk groups with distinct OS (p-value < 0.05 in all comparisons). In the validation cohort, median OS in the low (31%), intermediate-low (26%), intermediate-high (17%) and high risk (26%) were 15.7, 7.1, 1.8 and 1.0 months, respectively (p < 0.05 in all comparisons). Results were consistent following adjustment for subsequent treatment. In the external cohort, the PC-PI showed a C-statistic of 0.79 (95%CI 0.76–0.82), outperforming IPI and R-IPI. In conclusion, the PC-PI score is a novel tool for OS prediction and could facilitate risk-adapted management of LBCL patients relapsing after CAR T-cells. Additionally, these results will help stratification and interpretation of trials and real-world data incorporating CART-exposed patients.
ISSN:1756-8722

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