The efficacy of targeted and immune-based therapies in adults with TP53-mutated acute lymphoblastic leukaemia

We retrospectively evaluated the treatment outcomes of 47 adult patients with TP53-mutated acute lymphoblastic leukaemia (ALL) treated with either blinatumomab, inotuzumab or/and CD19 CAR T-cell therapy. The complete remission with or without count recovery (CR/CRi) (negative minimal residual disease (MRD-) rate) following treatment with blinatumomab (n = 46), inotuzumab (n = 26) and CD19 CAR T cells (n = 6) was 58.7% (96.3%), 61.5% (60%) and 66.7% (75%) respectively. The median OS was 13.6 months (95% CI: 9.6-17.2) for all patients, and it was not significantly different based on the individual novel salvage therapy (p = 0.40). The 12-month leukaemia-free survival (LFS) for responders to blinatumomab, InO and CAR T cells was 20%, 11% and 0% (p = 0.743) respectively. Patients who had undergone allogeneic haematopoietic stem cell transplantation (HSCT) post-response had improved 12-month LFS compared to those who did not (35% vs. 9%, p = 0.014). Among relapsed patients following blinatumomab, 11 (61%) presented with CD19-negative disease. Hence, targeted and immune-based therapies are effective in inducing high MRD-negative remission rates in adults with B-cell ALL harbouring TP53 mutations. Nonetheless, the durability of remission is short in the absence of allogeneic HCT consolidation and relapse frequently manifested as CD19-negative disease following blinatumomab.