Dp073 | a Multi-center Real-life Analysis on Patients With Large B-cell Lymphoma After Failure of Car-t Cells Therapy.
Year: 2025
Type: article
Abstract: Background CAR-T has changed treatment of relapsed/refractory (R/R) Large B Cell Lymphoma (LBCL), yet nearly 60% of patients (pts) relapse. While several options exist after CAR-T failure, their optimal use and accessibility remain unclear. We evaluate treatment strategies and outcomes in LBCL R/R after CAR-T. Methods We retrospectively analyzed LBCL pts treated post-CAR-T across 16 Fondazione Italiana Linfomi (FIL) centers. All received commercial CAR-T (axi-cel or tisa-cel) by Dec 31, 2023, with EBMT informed consent. Results Of 255 CAR-T recipients, 125 (65 axi-cel, 60 tisa-cel) relapsed or were refractory. Most had advanced stage (75%) and IPI≥3 (58%) disease. CRS occurred in 84% (12% severe), ICANS in 22% (9% severe). Relapse/progression was histologically confirmed in 50%, with CD19 loss in 51%. At relapse, 78% (n=97) received curative-intent therapy. Bispecific antibodies (BiAB) were planned in 65%, but only 19% eventually accessed them due to limited availability. Other therapies: polatuzumab-based regimens (27%), chemotherapy (22%), immunomodulatory agents (17%), radiotherapy (5%) and experimental drugs (10%). Median overall survival (OS) was 6.9 months in treated pts vs. 0.7 with palliative care (Fig1). BiAB (12 months OS) and polatuzumab regimens (8.7 m) outperformed chemotherapy (3.4 m, p=0.002). PFS was longest with BiAB (6 m) vs. polatuzumab (3.3), immunomodulants (1.9) or chemotherapy (1; p<0.001). Best responses were seen with BiAB (ORR 73%, CR 50%) and polatuzumab (ORR 37%, CR 33%). At infusion, bridging response, IPI, CARHEMATOTOX, stage, CRS, and ICANS impacted outcomes, but multivariate analysis confirmed only PET positivity at day 30. At failure, ECOG>1, LDH>2×ULN, >2 extranodal sites, relapse <4 months, platelets <100×10^9/L, and high EASIX predicted poor outcome. Multivariate analysis identified LDH, extranodal sites, and early relapse as OS predictors; LDH and early relapse for PFS. These factors defined prognostic models stratifying pts into 3 groups. The PC-PI score (based on ECOG, Hb, LDH, extranodal sites, early relapse) was also validated. Pts achieving CR post-salvage (n=39) had better PFS when consolidated with allotransplant (n=18; 22 vs. 12 months, p=0.004), though OS benefit was not significant. Conclusions CAR-T failure in R/R LBCL leads to poor outcomes. BiAB show best efficacy but limited access. Prognostic markers (LDH, extranodal disease, early relapse) may guide therapy. In responders, allotransplant improves PFS.
Authors: M. Farina, E. Maiolo, C. Ghiggi, P. Angelillo, M. Novo, F.M. Quaglia, L. Schiattone, G. Facchin, L. Mannelli, V. Tomarchio, E. Lucchini, L. Pagliaro, G. Scapinello, M. Marangon, S. Pelliccia, R. Sciarra, F. Zaja
Institutions: Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia, University of Brescia, Agostino Gemelli University Polyclinic, Ospedale Policlinico San Martino, IRCCS Ospedale San Raffaele, Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele, Azienda Ospedaliera Citta' della Salute e della Scienza di Torino, Azienda Ospedaliera Universitaria Integrata Verona, Ospedale di Santo Spirito, Azienda sanitaria universitaria Friuli Centrale, Azienda Usl Toscana Centro, Campus Bio Medico University Hospital, Azienda sanitaria universitaria Giuliano Isontina, University of Parma, University of Padua, Azienda Ospedale - Università Padova, Centro di Riferimento Oncologico, Sapienza University of Rome, Policlinico San Matteo Fondazione, University of Trieste
Language: English
Topic: CAR-T cell therapy research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7093123169
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