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Optimizing bridging therapies to CAR-T for children and young adults with R/R ALL

By Jennifer Reilly

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Feb 26, 2025

Learning objective: After reading this article, learners will be able to cite a new clinical development in ALL



CAR T-cell therapies have emerged as an effective treatment option for patients with R/R B-ALL. In the period between CAR T-cell eligibility and infusion, disease progression poses a significant risk, necessitating the use of bridging therapy to optimize outcomes.1 High-intensity bridging therapies are often used in patients with a higher tumor burden; however, their potential benefits need to be evaluated against increased treatment-related toxicities.

The impact of different bridging therapies prior to anti-CD19 CAR T-cell infusion was evaluated in a multinational retrospective study, comparing no systemic therapy, low-intensity, and high-intensity therapy in terms of OS, PFS, tumor burden, and adverse events in children and young adults (N = 88) with R/R B-ALL.1 Results from this analysis were published in the Journal of Hematology and Oncology by Breidenbach et al.1


Key learnings
OS was significantly improved in patients who received no bridging therapy compared to those who received low- (p = 0.0297) or high-intensity (p = 0.0307) bridging therapy. There was no significant difference in PFS among the groups.
Patients who received high-intensity bridging therapy experienced increased adverse events, including a higher rate of bacterial infections (p = 0.0052) and mucositis (p= 0.0108).
Patients receiving high-intensity bridging therapy had a higher tumor burden and higher MRD at baseline compared to the low-intensity/no therapy group.
These data suggest that low-intensity bridging may be preferable when clinically feasible, particularly in patients with manageable tumor burden; necessitating prospective studies to optimize bridging therapy in R/R B-ALL.

Abbreviations: B-ALL, B-cell lineage acute lymphoblastic leukemia; CAR, chimeric antigen receptor; MRD, measurable residual disease; OS, overall survival; PFS, progression-free survival; R/R, relapsed/refractory.

References

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