Abstract
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.
Highlights
Treatment of chronic myeloid leukemia (CML) has significantly changed over the last two decades with the development of tyrosine kinase inhibitors (TKIs) targeting BCR-ABL
Are Second-Generation TKIs More Efficient Than Imatinib to Treat CP-CML?. This is the first meta-analysis of second-generation BCR-ABL TKIs that provides long-term estimates on efficacy and safety compared to imatinib
The major finding of this meta-analysis of 14 randomized clinical trials (RCTs) including 4659 CML patients was that second-generation BCR-ABL TKIs did not significantly improve short- or long-term overall survival compared with imatinib
Summary
Treatment of chronic myeloid leukemia (CML) has significantly changed over the last two decades with the development of tyrosine kinase inhibitors (TKIs) targeting BCR-ABL. TKIs are approved to treat CML (a sixth BCR-ABL TKI, radotinib, is approved in Korea only). Cancers 2020, 12, 1242 them are indicated for use in newly diagnosed chronic-phase (CP) CML patients [1]. The first-generation TKI, imatinib is a well-known safe and effective drug, whereas second-generation TKIs (i.e., dasatinib, nilotinib or bosutinib) provide faster molecular responses but are considered less safe than imatinib [2,3]. The use of a second-generation TKI over imatinib is recommended for patients with moderate- or high-risk Sokal scores. Second-generation TKIs are recommended for young patients because of the higher probability of treatment-free remission with these TKIs [1]
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