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.

in Journal of hematology & oncology by 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

TLDR

  • The Post-CAR Prognostic Index (PC-PI) score is a novel prognostic model that can predict overall survival in relapsed/refractory large B-cell lymphoma patients who have failed CAR T-cell therapy.
  • The PC-PI score classified patients into four risk groups with distinct OS and outperformed IPI and R-IPI in the validation cohort.
  • Future studies could investigate the use of the PC-PI score in combination with other biomarkers to further improve treatment outcomes in LBCL patients.

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.

Overview

  • The study aimed to develop a prognostic model to predict overall survival (OS) for relapsed/refractory large B-cell lymphoma patients who have failed chimeric antigen receptor (CAR) T-cell therapy.
  • The study used a training cohort of 216 patients from 12 Spanish centers and an external validation cohort of 204 patients from three European centers to develop the Post-CAR Prognostic Index (PC-PI).
  • The PC-PI score incorporates five variables: ECOG scale, hemoglobin level, lactate dehydrogenase (LDH), number of extranodal sites, and time from CAR-T to progressive disease (PD).

Comparative Analysis & Findings

  • The study found that the PC-PI score classified patients into four risk groups with distinct OS: low risk (31%), intermediate-low (26%), intermediate-high (17%), and high risk (26%).
  • The median OS in the low, intermediate-low, intermediate-high, and high risk groups were 15.7, 7.1, 1.8, and 1.0 months, respectively.
  • The PC-PI score outperformed the International Prognostic Index (IPI) and Revised IPI (R-IPI) in predicting OS in the validation cohort, with a C-statistic of 0.79 (95%CI 0.76-0.82).

Implications and Future Directions

  • The PC-PI score can help identify high-risk patients who may benefit from more intensive treatment and improve patient selection for clinical trials.
  • Future studies could investigate the use of the PC-PI score in combination with other biomarkers to further stratify patients and improve treatment outcomes.
  • The PC-PI score could also be used to inform risk-adapted management strategies for LBCL patients relapsing after CAR T-cell therapy, such as early salvage therapy or palliative care.
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