Author(s): Ferdinand R, Mitchell SA, Batson S, Tumur I
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Abstract BACKGROUND: Chronic myeloid leukemia (CML) is a myeloproliferative disorder of blood stem cells. The tyrosine kinase inhibitor (TKI) imatinib was the first targeted therapy licensed for patients with chronic-phase CML, and its introduction was associated with substantial improvements in response and survival compared with previous therapies. Clinical trial data are now available for the second-generation TKIs (nilotinib, dasatinib, and bosutinib) in the first-, second-, and third-line settings. A qualitative systematic review was conducted to qualitatively compare the clinical effectiveness, safety, and effect on quality of life of TKIs for the management of chronic-, accelerated-, or blast-phase CML patients. METHODS: Included studies were identified through a search of electronic databases in September 2011, relevant conference proceedings and the grey literature. RESULTS: In the first-line setting, the long-term efficacy (up to 8 years) of imatinib has been confirmed in a single randomized controlled trial (International Randomized Study of Interferon [IRIS]). All second-generation TKIs reported lower rates of transformation, and comparable or superior complete cytogenetic response (CCyR), major molecular response (MMR), and complete molecular response rates compared with imatinib by 2-year follow-up. Each of the second-generation TKIs was associated with a distinct adverse-event profile. Bosutinib was the only second-generation TKI to report quality-of-life data (no significant difference compared with imatinib treatment). Data in the second- and third-line setting confirmed the efficacy of the second-generation TKIs in either imatinib-resistant or -intolerant patients, as measured by CCyR and MMR rates. CONCLUSION: Data from first-line randomized controlled trials reporting up to 2-year follow-up indicate superior response rates of the second-generation TKIs compared with imatinib. Current evidence from single-arm studies in the second-line setting confirm that nilotinib, dasatinib, and bosutinib are valuable treatment options for the significant subgroup of patients who are intolerant or resistant to imatinib treatment.
This article was published in J Blood Med
and referenced in Journal of Carcinogenesis & Mutagenesis