Tyrosine kinase inhibitors in Philadelphia chromosome–positive acute lymphoblastic leukemia (ALL): A systematic review and meta-analysis.

Abstract

e18522 Background: Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) is a rare, life threatening form of leukemia with unique challenges in diagnosis and treatment, and is historically associated with a poor prognosis. The introduction of tyrosine kinase inhibitor (TKI) agents has significantly altered paradigms; however, the relative efficacy between imatinib and standard chemotherapy or newer-generation TKI agents remains uncertain. In this quantitative synthesis, imatinib will be compared to both standard chemotherapy regimen, and newer generation TKIs such as dasatinib and ponatinib. Methods: Databases including PubMed and Cochrane Central were searched for potentially relevant studies, featuring a comparison of either imatinib versus standard non-TKI cytotoxic chemotherapy, or imatinib versus other TKI agents, including new-generation drugs like dasatinib and ponatinib. The included studies must report at least one of: (i) overall survival (OS), (ii) event-free survival (EFS), and (iii) adverse drug reactions. The meta-analysis was conducted via RevMan 5.4 with hazard ratio (HR) and 95% confidence interval (CI) computed. The inverse-variance method with the random-effects model were utilized. A p-value of < 0.05 was declared statistically significant. Results: A total of 9 studies were included in the pooled analysis. Imatinib was marginally inferior to newer TKI agents in terms of overall survival (HR: 1.85; 95% CI: 0.99-3.44; P = 0.05), whereas it was superior compared to non-TKI standard chemotherapy (HR: 0.34; 95% CI: 0.18-0.65; P = 0.001). Imatinib was non-inferior to newer TKI agents in terms of EFS (P = 0.57), whereas it was superior compared to non-TKI standard chemotherapy (HR: 0.35; 95% CI: 0.19-0.64; P = 0.0007). Both comparisons had a comparable incidence of adverse drug reactions, with no statistically significant differences observed. Conclusions: In patients with Ph+ ALL, TKI-based therapy significantly improves survival outcomes in comparison to non-TKI standard cytotoxic chemotherapy. While newer-generation TKIs may offer marginal OS advantage in comparison to imatinib, non-inferior EFS and adverse event rate continue to support its role as an effective treatment strategy. Further large-scale trials, particularly featuring comparisons between first-generation versus new-generation TKI agents, are necessary in order to arrive at a valid conclusion. Number of Studies Hazard Ratio (95% CI) P-value I 2 , % (P-value) Overall Survival Imatinib vs. TKI 2 1.85 (0.99 to 3.44) 0.05 0 (0.43) Imatinib vs. Standard 4 0.34 (0.18 to 0.65) 0.001 25 (0.26) Event-Free Survival Imatinib vs. TKI 3 1.22 (0.61 to 2.46) 0.57 75 (0.02) Imatinib vs. Standard 4 0.35 (0.19 to 0.64) 0.0007 36 (0.20) Adverse Drug Reactions Imatinib vs. TKI 3 1.01 (0.92 to 1.10) 0.89 0 (0.69) Imatinib vs. Standard 4 0.81 (0.60 to 1.10) 0.18 72 (0.01)