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 Journal Article
| Authors: | Iacoboni, G.; Navarro, V.; Sesques, P.; Rejeski, K.; Bastos-Oreiro, M.; Serpenti, F.; Martin Lopez, A. A.; Iraola-Truchuelo, J.; Delgado, J.; Perez, A.; Guerreiro, M.; Caballero, A. C.; Martinez-Cibrian, N.; Luzardo Henriquez, H.; Sanchez Pina, J. M.; Sancho, J. M.; Ghesquieres, H.; Mussetti, A.; Lopez Corral, L.; Hernani, R.; Reguera, J. L.; Sureda, A.; Bosch, F.; Martin Garcia-Sancho, A.; Kwon, M.; Subklewe, M.; Kuhnl, A.; Bachy, E.; Barba, P.; Villacampa, G.; Abrisqueta, P. |
| Article Title: | 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 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. © The Author(s) 2024. |
| Keywords: | adult; cancer chemotherapy; cancer survival; controlled study; aged; middle aged; young adult; major clinical study; overall survival; clinical feature; clinical trial; disease course; cancer growth; validation process; cancer patient; cancer radiotherapy; cohort studies; palliative therapy; cohort analysis; hemoglobin; retrospective study; risk factor; cancer center; disease progression; multicenter study; lactate dehydrogenase; lymphoma, large b-cell, diffuse; disease exacerbation; therapy; adoptive immunotherapy; immunotherapy, adoptive; electrocorticography; spain; external validity; score; procedures; diffuse large b cell lymphoma; cancer prognosis; extranodal extension; large b-cell lymphoma; humans; prognosis; human; male; female; article; prognostic assessment; car-t; tisagenlecleucel t; chimeric antigen receptor t-cell immunotherapy; axicabtagene ciloleucel; lisocabtagene maraleucel; third-line treatment |
| Journal Title: | Journal of Hematology & Oncology |
| Volume: | 17 |
| ISSN: | 1756-8722 |
| Publisher: | Biomed Central Ltd |
| Date Published: | 2024-10-29 |
| Start Page: | 102 |
| Language: | English |
| DOI: | 10.1186/s13045-024-01608-8 |
| PUBMED: | 39468591 |
| PROVIDER: | scopus |
| PMCID: | PMC11520873 |
| DOI/URL: | |
| Notes: | Source: Scopus |
