Journal of Hematology & Oncology (Oct 2024)

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,
  • 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

DOI
https://doi.org/10.1186/s13045-024-01608-8
Journal volume & issue
Vol. 17, no. 1
pp. 1 – 10

Abstract

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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 ( 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.

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