OUTCOMES of CAR T-CELL THERAPY (CART19) for B-ALL: A GOCART COALITION REPORT on BEHALF of the PDWP, ALWP, and CTIWP of the EBMT
Recommended Citation
Maldonado VO, Galimard J, Ottaviano G, Alonso-Saladrigues A, Farhan S, Vuyyala S, Michel E, Imran F, Sánchez Sierra N, Martinez-Cibrián N, Ryhänen S, Mitchell R, Mielke S, Petersen SL, Sirvent A, Pabst T, Kuball J, Barba P, Pérez-Martínez A, Attarbaschi A, Nagler A, Pérez-Simón JA, von Bonin M, Nicholson E, Beuvais D, Sora F, Paganessi M, Penack O, Castilla Llorente C, Beguin Y. OUTCOMES of CAR T-CELL THERAPY (CART19) for B-ALL: A GOCART COALITION REPORT on BEHALF of the PDWP, ALWP, and CTIWP of the EBMT. Bone Marrow Transplant 2025; 60:50-52.
Document Type
Conference Proceeding
Publication Date
11-5-2025
Publication Title
Bone Marrow Transplant
Keywords
blinatumomab, brexucabtagene autoleucel, tisagenlecleucel T, varnimcabtagene autoleucel, adult, aged, apheresis, B cell acute lymphoblastic leukemia, bridging therapy, child, chimeric antigen receptor T-cell immunotherapy, conference abstract, cytogenetics, female, follow up, human, major clinical study, male, relapse, retrospective study, risk factor
Abstract
Background: Since 2017, two industrial CART19 products, Kymriah and Tecartus, have been commercialized in the EU, revolutionizing the management of R/R B-ALL in Europe. Other academic CART19 products have been successfully manufactured, filling accessibility gaps across centres. Here, we present long-term outcomes and risk factors for alloHCT-naïve and alloHCT-exposed B-ALL patients receiving CART19 therapy. Methods: Outcomes of adult and paediatric B-ALL patients receiving commercial or academic autologous CART19 therapy were collected from the EBMT registry. Data were reported from 17 countries from 2016 to 2023. Safety and efficacy were retrospectively assessed as per ASTCT 2019 consensus grading and NCCN guidelines. The data cut-off for follow-up was June 2024. Results: A total of 345 B-ALL patients (173 adults and 172 paediatrics) received therapy with Kymriah (65%), ARI-0001 (26%), Tecartus (5.5%), and others (3.5%), with a reverse Kaplan-Meier median follow-up of 2.2 years. Median age at infusion was 18 yrs (range, 1.1-78.2) and 41.7% were females. Baseline features included high-risk cytogenetics in 34%, prior allo-HCT (alloHCT-exposed) in 57%, ≥3 treatment lines in 55%, and overt haematological disease in 70% of patients. Bridging therapy was administered in 86% of patients. Following CART19 infusion, any grade (and severe) CRS was 71.6% (14.5%), and for ICANS was 15.7% (7.6%). The cumulative incidence of MRD-negative CR at 3 months was 78% (73.1-82.1), with a 2-year OS and LFS of 64.7% (58.9-70) and 48.2% (42.3-53.9), respectively. Despite comparable CRR, OS and LFS, univariate and multivariate analysis revealed a differing impact of pre-treatment factors in alloHCT-naïve vs alloHCT-exposed CART19 patients. Univariate analysis found no impact for age, sex, high-risk cytogenetics and number of prior treatment lines on 2-year OS and LFS in both alloHCT-naïve and alloHCT-exposed patients. Prior blinatumomab refractoriness was associated with worse 2-year OS and LFS in comparison to blinatumomab-responsive patients (83% vs. 31% and 60% vs. 16%, respectively; p≤ 0.003) in alloHCT-naïve patients. Notably, this association was lost in alloHCT-exposed patients, with no impact for prior blinatumomab exposure and response. Prior inotuzumab refractoriness was strongly associated with worse 2-year OS and LFS for both alloHCT-naïve and alloHCTexposed patients (p ≤ 0.003), although inotuzumab-responsive and inotuzumab-naïve patients showed comparable outcomes. Leukemia control (morphological disease vs. CR) in alloHCT-naïve patients was strongly correlated with 2-year OS and LFS, with the best outcomes observed in MRD-negative CR patients, both at apheresis (83% and 83%; p ≤ 0.02) and lymphodepletion (100% and 79%; p < 0.0001). Notably, this significance of leukemia control was lost in alloHCTexposed patients, as confirmed by multivariate analysis (table). Finally, alloHCT-exposed patients reaching CART19 after an early alloHCT-relapse (<6 months from alloHCT) associated with worse 2-year OS (74% vs. 43%) and LFS (53% vs. 30%) (p ≤ 0.001) (figure), confirmed in the multivariate analysis. Conclusions: Commercial and academic CART19 therapy remains an effective treatment for adult and paediatric B-ALL patients. This «real-world» study suggests that efficacy is more impacted by prior refractoriness and disease burden than by age, preceding therapy, or cytogenetics. Also, the relevance of preceding factors and the biology affecting CART19 therapy might be different for alloHCTnaïve and alloHCT-exposed patients. (Table present) (Figure present).
Volume
60
First Page
50
Last Page
52
