Combination of Ponatinib and Blinatumomab in Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia

OBJECTIVES: Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) is traditionally treated with tyrosine kinase inhibitors (TKIs) alongside chemotherapy. Recent studies suggest that combining ponatinib and blinatumomab may offer a highly effective, chemotherapy-free alternative. We performed this study to assess the efficacy and safety of ponatinib combined with blinatumomab in adult patients with Ph+ ALL, across both newly diagnosed and relapsed/refractory settings. METHODS: This systematic review and meta-analysis included 8 studies evaluating ponatinib plus blinatumomab in Ph+ ALL. Primary outcomes were overall survival (OS) and event-free survival (EFS). Secondary outcomes included complete molecular response (CMR), relapse rates, hematologic response, and adverse events (AEs). Risk of bias was assessed using the Newcastle-Ottawa Scale. Analyses were conducted using a random-effects model. RESULTS: The pooled OS was 84%, with higher survival in newly diagnosed patients (93%) versus refractory cases (50%). EFS was 64% overall, with 86% in the newly diagnosed subgroup. The pooled CMR rate was 89%, and hematologic response reached 93%. Relapse rates were low, particularly in frontline settings. The pooled AE rate was 17%, decreasing to 11% after sensitivity analysis, indicating a manageable safety profile. CONCLUSIONS: Ponatinib combined with blinatumomab demonstrates high efficacy and tolerability as a frontline, chemotherapy-free regimen in Ph+ ALL. These findings support further investigation in larger, randomized trials to confirm long-term outcomes and solidify its place in standard treatment protocols.