First-line treatment strategies for newly diagnosed chronic myeloid leukemia: a network meta-analysis

OBJECTIVES: With bosutinib proven to be available for frontline treatment, there are currently four frontline treatments as well as an additional strategy with high-dose imatinib for newly diagnosed chronic myeloid leukemia (CML). Due to the lack of direct comparison of high-dose imatinib, dasatinib, nilotinib, and bosutinib, we summarized the evidence to indirectly compare the efficacy among these treatment options. METHODS: In total, 14 randomized clinical trials including 5,630 patients were analyzed by direct and mixed-treatment comparisons. Outcomes assessed were the following: complete cytogenetic response at 12 months; major molecular response at 12, 24, and 36 months; deep molecular response at 12, 24, 36, and 60 months; early molecular response at 3 months; progression-free survival (PFS); overall survival (OS); and Grade 3 or 4 adverse events (AEs). RESULTS: The Bayesian network meta-analysis demonstrated that high-dose imatinib was less effective than all new-generation tyrosine kinase inhibitors and had a higher probability of Grade 3 or 4 AEs. For molecular response, 300 mg of nilotinib was likely to be the preferred frontline treatment, as demonstrated by higher response rates and faster, deeper, and longer molecular response. For PFS and OS, there were high likelihoods (79% and 74%, respectively) that 400 mg of nilotinib was the preferred option. For AEs, standard-dose imatinib has the highest probability (65%) of being the most favorable toxicity profile. CONCLUSION: Considering the efficacy and toxicity profile, it is not recommended to use high-dose imatinib for treatment. This analysis also showed that nilotinib has the highest probability to become the preferred frontline agents for treating CML.