Ferdinand Roxanne, Mitchell Stephen A, Batson Sarah, Tumur Indra
Pfizer, Tadworth, UK.
J Blood Med. 2012;3:51-76. doi: 10.2147/JBM.S33380. Epub 2012 Aug 3.
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.
Included studies were identified through a search of electronic databases in September 2011, relevant conference proceedings and the grey literature.
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.
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.
慢性髓性白血病（CML）是一种血液干细胞的骨髓增殖性疾病。酪氨酸激酶抑制剂（TKI）伊马替尼是首个被批准用于慢性期CML患者的靶向治疗药物，与既往治疗相比，其应用使缓解率和生存率有了显著提高。目前已有第二代TKI（尼罗替尼、达沙替尼和博舒替尼）在一线、二线和三线治疗中的临床试验数据。进行了一项定性系统评价，以定性比较TKI治疗慢性期、加速期或急变期CML患者的临床疗效、安全性及对生活质量的影响。
通过检索2011年9月的电子数据库、相关会议论文集和灰色文献来确定纳入研究。
在一线治疗中，一项单中心随机对照试验（国际干扰素随机研究[IRIS]）证实了伊马替尼的长期疗效（长达8年）。所有第二代TKI均报告转化率较低，且在2年随访时，与伊马替尼相比，完全细胞遗传学缓解（CCyR）、主要分子学缓解（MMR）和完全分子学缓解率相当或更高。每种第二代TKI都有独特的不良事件谱。博舒替尼是唯一报告了生活质量数据的第二代TKI（与伊马替尼治疗相比无显著差异）。二线和三线治疗的数据证实了第二代TKI在伊马替尼耐药或不耐受患者中的疗效，以CCyR和MMR率衡量。
一线随机对照试验长达2年随访的数据表明，第二代TKI的缓解率优于伊马替尼。二线治疗单臂研究的当前证据证实，尼罗替尼、达沙替尼和博舒替尼对于伊马替尼治疗不耐受或耐药的显著亚组患者是有价值的治疗选择。
