Long-Term Survival, Vascular Occlusive Events and Efficacy Biomarkers of First-Line Treatment of CML: A Meta-Analysis

Large randomized clinical trials and prior meta-analyses indicate that second-generation BCR-ABL tyrosine kinase inhibitors (TKIs) improve surrogate biomarkers in patients with chronic myeloid leukemia (CML) without providing survival benefits. The objective is to evaluate the long-term efficacy and the occurrence of vascular occlusion with second-generation BCR-ABL TKIs compared with imatinib in patients with CML. Three scientific databases, a clinical registry and abstracts from congress were searched to identify all randomized controlled trials that compared a second-generation BCR-ABL TKI to imatinib in patients with CML. Outcomes extracted were overall survival, major molecular response and complete cytogenetic response, arterial occlusive events and venous thromboembolism. These data were synthesized by odds ratios using a fixed-effect model. This meta-analysis included 4659 participants from 14 trials. Second-generation BCR-ABL TKIs did not improve overall survival compared with imatinib, even at longer follow-up (OR, 1.17 (95% CI, 0.91-1.52)). They improved surrogate biomarkers at 12 and 24 months but increased the risk of arterial occlusion (ORPETO, 2.81 (95% CI, 2.11-3.73)). The long-term benefits of second-generation TKIs are restricted to surrogate outcomes and do not translate into prolonged survival compared to imatinib. Given the long-term use, frontline therapy should be chosen carefully, with special attention to the patients' quality of life and cardiovascular risks.