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Impact of TP53 mutations on treatment failure patterns in patients treated with blinatumomab

By Dylan Barrett

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Feb 17, 2025

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



Blinatumomab, a bispecific CD3×CD19 T-cell engager, is an effective therapy for patients with B-ALL; however, the role of disease biology in relapse patterns remains unclear.1

A retrospective analysis of 267 adult patients with B-ALL treated at City of Hope who received ≥1 cycle of blinatumomab assessed the impact of patient and clinical factors and leukemia genetics.1 Results from this analysis were presented at the 66th ASH Annual Meeting and Exposition by Aldoss.1


Key learnings
Among R/R patients (n = 150), only pre-treatment high disease burden and EMD were associated with lower CR/CRi rates (47.3% with ≥50% BM blasts vs 80.4% with 5–49% BM blasts; p <0.01; and 13.3% vs 64.4% with vs without EMD; p <0.01) .
Patients with TP53 mutations (13.1%) had an increased risk of CD19− relapse (HR, 6.84; 95% CI, 2.68–17.45; p <0.01), whilst patients who received allo-HSCT consolidation had a reduced risk of CD19− relapse (HR, 0.10; 95% CI, 0.03–0.37; p <0.01) and EMD relapse (HR, 0.36; 95% CI, 0.18–0.73; p <0.01).
Patients with TP53 mutations had inferior LFS vs patients with no TP53 mutations (p = 0.0014), whilst patients who received blinatumomab and were MRD+ had improved LFS vs patients who were R/R, including in patients with TP53 mutations (p = 0.00032).
Despite not impacting the initial response to blinatumomab, TP53 mutations may predict treatment failure after initial response, particularly CD19− relapse. These findings may impact on choice of CD19-directed immunotherapy for TP53 mutated B-ALL.

Abbreviations: allo-HSCT, allogeneic hematopoietic stem cell transplantation; ASH, American Society of Hematology; B-ALL, B-cell acute lymphoblastic leukemia; BM, bone marrow; CI, confidence interval; CR, complete remission; CRi, CR with incomplete count recovery; EMD, extramedullary disease; HR, hazard ratio; LFS, leukemia-free survival; MRD, measurable residual disease; R/R, relapsed/refractory.

References

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