Background Outcomes after CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy failure in relapsed or refractory large B-cell lymphoma (LBCL) remain poor, and prognostic tools to guide subsequent management are limited. We evaluated real-world outcomes after CAR-T failure and developed clinical prediction models (CPMs) for survival after subsequent anti-cancer therapy. Methods We conducted a single-center retrospective cohort study of adult patients with LBCL treated with CD19-directed CAR-T therapy at Oregon Health & Science University between 2016 and 2024. Patients experiencing relapse or progression after CAR-T therapy were included. Overall survival from relapse/progression (OS1) and from initiation of subsequent anti-cancer therapy (OS2) were evaluated. Cox proportional hazards models were used to develop CPMs for 1-year OS among patients receiving subsequent therapy. Results Among 187 patients treated with CD19-directed CAR-T therapy, 100 (53%) experienced treatment failure. Sixty-eight patients received subsequent anti-cancer therapy and were included in prognostic analyses. Median OS1 was 5.07 months (95% CI, 3.71-8.58). Patients receiving subsequent therapy had significantly improved OS compared with those who did not receive further treatment (median OS1, 9.94 vs. 0.74 months; p < 0.001). Among treated patients, median OS2 was 8.34 months (95% CI, 6.73-20.1), with no significant differences across treatment strategy groups or treatment eras. The best-performing CPM incorporated time from CAR-T infusion to subsequent therapy, lactate dehydrogenase level, and Eastern Cooperative Oncology Group performance status, demonstrating good discrimination (c-statistic, 0.771) and calibration after internal validation. Conclusions Outcomes after CAR-T failure in LBCL remain poor despite the availability of multiple salvage treatment strategies. Time to relapse after CAR-T therapy was the strongest prognostic factor. The proposed CPMs may provide a practical framework for risk stratification and support clinical decision-making and clinical trial selection pending external validation.
S. Kungwankiattichai, Sanjog Bastola, Manoj Rai et al.· Transplantation and Cellular...· 0 citations
BACKGROUND
Chimeric antigen receptor T-cell (CAR-T) therapies targeting CD19 have demonstrated effectiveness in the treatment of relapsed/refractory B-cell malignancies. Several CAR-T therapies have been approved in the United States, including axicabtagene ciloleucel (axi-cel), for relapsed/refractory diffuse large B-cell lymphoma (DLBCL), and brexucabtagene autoleucel (brexu-cel), for B-cell precursor acute lymphoblastic leukemia and mantle cell lymphoma (MCL). However, use of CAR-T therapies can result in potentially severe adverse effects such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS).
OBJECTIVE
This analysis of real-world data evaluated the incidence and management of CRS and ICANS in patients with B-cell malignancies following treatment with axi-cel or brexu-cel therapy.
STUDY DESIGN
This retrospective observational cohort study analyzed data from the Center for International Blood and Marrow Transplant Research (CIBMTR). Adult patients in the United States who received axi-cel or brexu-cel for any indication from October 2020 to December 2021 with ≥1 follow-up visit were included. The main outcome of interest was incidence of CRS and ICANS following CAR-T therapy, graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) guidelines. Management of CRS and ICANS with preventive therapies and treatments administered following development of CRS and ICANS was also investigated.
RESULTS
Overall, 927 patients across 87 US centers were included (axi-cel, n=707 [76.3%]; brexu-cel, n=220 [23.7%]). Median (range) age was 63 (19-89) years, and 65.3% (605/927) were male. Most patients (83.3% [n=589]) received axi-cel for diffuse large B-cell lymphoma or transformed follicular lymphoma. All patients who received brexu-cel had mantle cell lymphoma. Overall, 766 (82.6%) patients developed CRS (grade ≥2, 47.0%; 360/766). Of patients with available data, 12.4% (89/715) received CRS preventive therapy, most commonly with tocilizumab alone (79.8%; 71/89). Of patients who developed CRS, 76.6% (587/766) received CRS treatment, including 63.5% (258/406) of patients with grade 1 and 91.4% (329/360) with grade ≥2. The most common treatment was tocilizumab (97.3%; 571/587), alone or in combination. Of patients with available data, 49.8% (356/715) received ICANS prevention, mostly anti-epileptics alone (93.3%; 332/356). Of 876 evaluable patients, 424 (48.4%) developed ICANS (grade ≥2, 71.5%; 303/424). Of these, 85.6% (363/424) received treatment for ICANS, most commonly corticosteroids (92.3%; 335/363).
CONCLUSIONS
Rates of CRS (82.6%) and ICANS (48.4%) were consistent with incidences expected based on prescribing information for axi-cel and brexu-cel, highlighting potential burdens of CAR-T therapy. These results also stress the importance of continuous patient monitoring and management during CAR-T therapy and demonstrate an evolving treatment landscape, including more aggressive management of CRS and interest in preventive therapies for CRS and ICANS.
M. Frigault, R. Maziarz, T. Amoloja et al.· Transplantation and Cellular...· 0 citations
Cellular and gene therapy (CGT) has fundamentally reshaped the treatment landscape for a growing range of malignant and non-malignant diseases. Yet the rapid expansion of CGT has also exposed critical institutional and system-level pressures, including constraints in infrastructure and workforce capacity, product manufacturing, patient access, regulatory and data reporting compliance, and long-term healthcare affordability and sustainability. These opportunities and challenges framed the joint plenary session sponsored by the American Society for Transplantation and Cellular Therapy (ASTCT), the Center for International Blood and Marrow Transplant Research (CIBMTR), and the European Society for Blood and Marrow Transplantation (EBMT) at the 2026 ASTCT-CIBMTR Tandem Meetings. This proceedings manuscript summarizes the key challenges inherent to CGT expansion, identifies priority areas for coordinated action, and issues a call to the field to address these needs with urgency and shared commitment.
Jeffery J. Auletta, Á. Urbano-Ispizua, R. Maziarz et al.· Transplantation and Cellular...· 0 citations
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