Relapse remains the leading cause of treatment failure in pediatric and young adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL) undergoing chimeric antigen receptor T-cell (CAR-T) therapy. While prognostic factors for relapse have been identified, further refinement is needed. We conducted a single-center retrospective study of 69 patients treated with Tisagenlecleucel, to evaluate the prognostic impact of TP53 alterations (TP53Alt), including mutations and/or deletions. Among 49 patients with available samples, 17 (34.7%) had TP53Alt. These patients showed significantly lower remission rates (68.8% vs. 93.8%, p = 0.033) and worse event-free survival (EFS) and overall survival (OS), independent of genetic risk group. Median EFS was 3.8 months (95% CI: 1.2–NE) for TP53Alt versus 50.9 months (95% CI: 23.9–NE) for TP53 wild-type (TP53wt). Three-year EFS and OS were 33.1% (95% CI: 16.4%–66.6%) and 37.2% (95% CI: 19.4%–71.4%) for TP53Alt, compared to 56.2% and 81.2% for TP53wt (p = 0.0069 and p = 0.0010, respectively). These findings identify TP53 alterations as a strong adverse prognostic factor in patients with r/r B-ALL treated with CAR-T therapy. Screening for TP53Alt may guide risk-adapted strategies, including early consolidation with hematopoietic stem cell transplantation or alternative therapies.
Alonso-Saladrigues et al. (Sat,) studied this question.
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