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Impact of TP53 mutations on treatment failure patterns in patients treated with blinatumomab
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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.
- Aldoss I. TP53 mutations increased the risk of CD19 negative relapse following blinatumomab in adults with B-cell acute lymphoblastic leukemia (B-ALL). Oral abstract #729. 66th American Society of Hematology Annual Meeting and Exposition; Dec 7–10, 2024; San Diego, US.
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