Efficacy and safety of combination therapy of ponatinib and blinatumomab in Philadelphia chromosome-positive acute lymphoblastic leukemia: A systematic review and meta-analysis.

Abstract

e15124 Background: Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) accounts for 20–30% of adult ALL cases and is characterized by high mortality and aggressive progression. Standard treatments with tyrosine kinase inhibitors (TKIs) and chemotherapy often lead to severe side effects. Recent innovations, such as the third-generation TKI ponatinib and the T-cell stimulator blinatumomab, promise to reduce mortality and treatment-related adverse events. This study evaluates their effectiveness and tolerability in the treatment of Ph+ ALL. Methods: A systematic search of PubMed, Embase, Scopus, and Cochrane databases was conducted from inception until December 2024. Statistical pooling was performed using OpenMeta Software (version 5.3) and a random-effects model. Occurrence rates were pooled with 95% confidence intervals. Heterogeneity was evaluated using I² and χ² statistics, with I² > 50% considered significant. Sensitivity and subgroup analyses were performed to address heterogeneity. Results: Seven studies met the eligibility criteria, yielding a total of 338 patients (294 newly diagnosed and 44 refractory) with a mean age of 52.43 years (SD: 15.21). Pooled analysis revealed the following findings: the overall survival rate at 24 months was 84% (95% CI: 0.751–0.930; I² = 79.7%; P < 0.001), while the disease relapse rate remained low at 11% (95% CI: 0.037–0.196; I² = 82%; P = 0.000). A statistically significant progression-free survival rate of 62% was observed over a 24-month follow-up period (95% CI: 0.353–0.896; I² = 94.15%; P = 0.000). Subgroup analysis identified that the heterogeneity was caused by the inclusion of newly diagnosed patients. After 24 months, 51% of patients (95% CI: 0.264–0.759; I² = 96.99%; P = 0.000) achieved a hematologic complete response (CR), with heterogeneity reported in both subgroups, i.e., refractory (I² = 98.67%) and newly diagnosed patients (I² = 92.18%). Similarly, the complete molecular response (CMR) rate at 24 months was 87% (95% CI: 0.792–0.964; I² = 76.06%; P = 0.000). Subgroup analysis showed that newly diagnosed patients had a CMR rate of 84% (95% CI: 0.727–0.953; I² = 75.86%; P = 0.006). Additionally, the incidence of grade 1–4 adverse events remained low, at 16% (95% CI: 0.055–0.282; I² = 77.51%; P = 0.004). In contrast, the rate of negative measurable residual disease was 78% (95% CI: 0.677–0.896; I² = 75.91%; P = 0.006), which was statistically insignificant. Conclusions: The combination of ponatinib and blinatumomab shows promising results in achieving event-free survival, overall survival, and complete molecular response in Ph+ ALL patients, with a manageable safety profile (16% adverse effects) at 24 months. However, well-defined studies with larger sample sizes are needed for definitive conclusions.