Impact of TP53 alterations on outcomes in pediatric and YA patients with R/R B‑ALL after CAR T‑cell therapy

Results from a single-center retrospective study, evaluating the prognostic impact of TP53 alterations (TP53^alt) in 69 pediatric and young adult (YA) patients with relapsed/refractory (R/R) B‑cell acute lymphoblastic leukemia (B‑ALL) treated with tisagenlecleucel, were recently published in Bone Marrow Transplantation by Alonso-Saladrigues et al. Endpoints included response rates, event-free survival (EFS), and overall survival (OS).

Key data: Among 49 patients in whom TP53^alt could be analyzed, 24.5% had TP53 mutation (TP53^mut), 24.5% had TP53 deletion (TP53^del), and 16.3% had both alterations. Complete remission rates were significantly lower in patients with TP53^alt vs wild-type (WT) TP53 (68.8% vs 93.8%; p = 0.033). The 3‑year EFS and 3‑year OS were 33.1% vs 56.2% (p = 0.0069) and 37.2% vs 81.2% (p = 0.0010) in patients with TP53^alt vs WT TP53, respectively. In multivariable analysis, TP53^mut remained the only independent variable that could predict inferior EFS (p = 0.012) and OS (p = 0.0056).

Key learning: TP53^alt represent a strong, independent adverse prognostic biomarker for tisagenlecleucel in pediatric and YA patients with R/R B‑ALL. Routine TP53 screening is recommended to guide risk-adapted strategies, including early consolidation with allogeneic hematopoietic stem cell transplantation (allo-HSCT) or alternative therapies.