1. 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.
- Author
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Iacoboni, Gloria, Navarro, Víctor, Sesques, Pierre, Rejeski, Kai, Bastos-Oreiro, Mariana, Serpenti, Fabio, Martin Lopez, Ana Africa, Iraola-Truchuelo, Josu, Delgado, Javier, Perez, Ariadna, Guerreiro, Manuel, Caballero, Ana Carolina, Martinez-Cibrian, Nuria, Luzardo Henriquez, Hugo, Sanchez Pina, Jose Maria, Sancho, Juan-Manuel, Ghesquieres, Hervé, Mussetti, Alberto, Lopez Corral, Lucia, and Hernani, Rafael
- 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. Key points: Key point #1: The Post-CAR Prognostic Index (PC-PI) is a tool to inform on overall survival after CAR T-cell progression in large B-cell lymphoma patients. Key point #2: The PC-PI can help risk-stratification and interpretation of trials and real-world data of regimens incorporating CART-exposed patients. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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