Comparative efficacy and safety of different doses of ponatinib versus other tyrosine kinase inhibitors for the treatment of chronic myeloid leukemia: a systematic review and network meta-analysis

ABSTRACTObjective Ponatinib was recommended with caution because of its high risk of causing arterial occlusion events in chronic myeloid leukemia (CML) patients. The purpose of this study was to understand the efficacy and safety of different doses of ponatinib in the treatment of CML, and to compare it with other tyrosine kinase inhibitors (TKIs).Method A network meta-analysis (NMA) was conducted by searching randomized controlled trials (RCTs) of ponatinib in patients with CML to compare the efficacy and safety of ponatinib, and ranked under the cumulative ranking curve (SUCRA) to evaluate the optimal treatment.Results A total of seven articles with eight RCTs were included in this study, involving 45 mg, 30 mg and 15 mg ponatinib doses. Seven outcome indexes were analyzed. The results showed that 45 mg ponatinib was superior to other doses of ponatinib and other TKIs in CCyR, MCyR and CHR, but the incidence of SAEs and AOEs was significantly higher than other treatment regimens.Conclusion Ponatinib, with an initial dosage of 45 mg and a gradual reduction to 15 mg, may be a more favorable option for patients with CML at all stages of disease progression, rather than just those in the chronic phase of CML.KEYWORDS: PonatinibCMLefficacysafetynetwork meta-analysis Declaration of interestsThe authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.Reviewer disclosuresOne reviewer is a speaker and advisory board member for Incyte, manufacturer of ponatinib. The remaining reviewers have no other relevant financial relationships or otherwise to disclose.Author contributionsStudy concept and design: Jian Li, Huaijun Tu.Data extraction: Hurong Lai1, Huijun Chen, Shan Zhang.Statistical analysis and interpretation: Shan Zhang, Jingyu Wang.Drafting of the manuscript: Shan Zhang, Jian Li, Huaijun Tu, Jian Li.All the authors read and approved the final manuscript and agree to be accountable for all aspects of the workSupplementary materialSupplemental data for this article can be accessed online at https://doi.org/10.1080/14740338.2023.2273339.Additional informationFundingThis paper was funded by a grant from the National Natural Science Foundation of China [81760033]; [82160030].