Treatment failure patterns in early versus late introduction of CAR T-cell therapy in large B-cell lymphoma Journal Article
| Authors: | Corona, M.; Ip, A.; Brown, S.; Luna, A.; Khatib, H.; Flynn, J. R.; Devlin, S. M.; Landego, I.; Cassanello, G.; Rejeski, K.; Zuckerman, T.; Dahi, P. B.; Scordo, M.; Lin, R. J.; Kabat, M.; Luttwak, E.; Pavkovic, E.; Palomba, M. L.; Park, J.; Salles, G.; Schoder, H.; Leithner, D.; Leslie, L. A.; Perales, M. A.; Beyar-Katz, O.; Shah, G. L.; Shouval, R. |
| Article Title: | Treatment failure patterns in early versus late introduction of CAR T-cell therapy in large B-cell lymphoma |
| Abstract: | CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy has recently been approved as second-line treatment for relapsed/refractory large B-cell lymphoma (LBCL). This study compares patterns of disease relapse and progression across patients receiving CAR-T as second-line (early administration) versus third or subsequent lines (late administration). We analyzed 354 patients treated with Axicabtagene ciloleucel (71%) and Lisocabtagene maraleucel (29%); 80 (23%) received early administration, and 274 (77%) late administration. One-year overall survival was higher in the early group (82% [95% CI 72–93] vs. 71% [95% CI 66–77], p = 0.048). However, the survival benefit was not sustained in multivariable Cox regression modeling and propensity score matching. One-year cumulative incidences of relapse were similar (37% [95% CI 24–50] vs. 43% [95% CI 37–49], p = 0.2), as were 1-year progression-free survival probabilities (62% [95% CI 50–76] vs. 50% [95% CI 44–57], p = 0.14). The early group exhibited a favorable toxicity profile, with lower rate of grade ≥2 cytokine release syndrome (26% vs. 39%, p = 0.031) and reduced cumulative incidence of severe neutropenia (41% [95% CI 30–52] vs. 55% [95% CI 49–60], p = 0.027). Our results indicate favorable outcomes with CAR-T irrespective of treatment line. The equivalence in disease control suggests that CAR-T resistance mechanisms persist in LBCL failing first-line therapy. © The Author(s), under exclusive licence to Springer Nature Limited 2025. |
| Keywords: | adult; aged; middle aged; treatment failure; retrospective studies; mortality; retrospective study; lymphoma, large b-cell, diffuse; therapy; adoptive immunotherapy; immunotherapy, adoptive; procedures; diffuse large b cell lymphoma; humans; human; male; female |
| Journal Title: | Bone Marrow Transplantation |
| Volume: | 60 |
| Issue: | 4 |
| ISSN: | 0268-3369 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2025-04-01 |
| Start Page: | 491 |
| End Page: | 498 |
| Language: | English |
| DOI: | 10.1038/s41409-025-02519-z |
| PUBMED: | 39893244 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledge in the PDF -- Corresponding authors is MSK author: Roni Shouval -- Source: Scopus |
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