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
Gloria Iacoboni, Vı́ctor Navarro, Pierre Sesques, Kai Rejeski, Mariana Bastos‐Oreiro, Fabio Serpenti, Ana África Martín López, Josu Iraola‐Truchuelo, Javier Delgado, Ariadna Pérez, Manuel Guerreiro, A Caballero, Núria Martínez‐Cibrián, Hugo Luzardo Henriquez, José María Sánchez Pina, Juan‐Manuel Sancho, Hervé Ghesquières, Alberto Mussetti, Lucía López‐Corral, Rafael Hernani, Juan Luis Reguera, Anna Sureda, Francesc Bosch, Alejandro Martı́n, Mi Kwon, Marion Subklewe, Andrea Kühnl, Emmanuel Bachy, Pere Barba, Guillermo Villacampa, Pau Abrisqueta
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.