Brümmendorf Tim H, Cortes Jorge E, de Souza Cármino Antonio, Guilhot Francois, Duvillié Ladan, Pavlov Dmitri, Gogat Karïn, Countouriotis Athena M, Gambacorti-Passerini Carlo
Universitätsklinikum Aachen, RWTH Aachen, Aachen, Germany; Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany.
Br J Haematol. 2015 Jan;168(1):69-81. doi: 10.1111/bjh.13108. Epub 2014 Sep 8.
Bosutinib is an oral, dual SRC/ABL1 tyrosine kinase inhibitor for resistant/intolerant chronic myeloid leukaemia (CML). We assessed the efficacy and safety of bosutinib 500 mg/d (n = 250) versus imatinib 400 mg/d (n = 252) after >24 months from accrual completion in newly diagnosed chronic phase (CP)-CML (Bosutinib Efficacy and Safety in Newly Diagnosed CML trial [BELA]). Cumulative complete cytogenetic response (CCyR) rates by 24 months were similar (bosutinib, 79%; imatinib, 80%); cumulative major molecular response (MMR) rates were 59% for bosutinib and 49% for imatinib. Responses were durable; 151/197 vs. 172/204 and 125/153 vs. 117/131 responders remained on treatment and maintained CCyR and MMR, respectively. Since the 12-month primary analysis, no new accelerated-/blast-phase transformations occurred with bosutinib; four occurred with imatinib. Early response (BCR-ABL1/ABL1 ≤ 10%, 3 months) was associated with better CCyR and MMR rates by 12 and 24 months (both arms). Gastrointestinal events and liver function test elevations were more common, and neutropenia, musculoskeletal events and oedema were less common with bosutinib. Discontinuations due to adverse events were more common with bosutinib versus imatinib (most commonly alanine aminotransferase elevation: 4% vs. <1%); most occurred within the first 12 months. Cardiovascular adverse events were similar in both arms. Bosutinib continues to demonstrate good efficacy and manageable tolerability in newly diagnosed CP-CML patients.
博舒替尼是一种口服的双重SRC/ABL1酪氨酸激酶抑制剂，用于治疗耐药/不耐受的慢性髓性白血病（CML）。我们在新诊断的慢性期（CP）-CML患者入组完成超过24个月后，评估了500 mg/d博舒替尼（n = 250）与400 mg/d伊马替尼（n = 252）的疗效和安全性（新诊断CML的博舒替尼疗效和安全性试验[BELA]）。24个月时的累积完全细胞遗传学缓解（CCyR）率相似（博舒替尼为79%；伊马替尼为80%）；博舒替尼的累积主要分子学缓解（MMR）率为59%，伊马替尼为49%。缓解持续存在；分别有151/197和172/204例、125/153和117/131例缓解者继续接受治疗并维持CCyR和MMR。自12个月的初步分析以来，接受博舒替尼治疗的患者未发生新的加速期/急变期转化；接受伊马替尼治疗的患者发生了4例。早期缓解（3个月时BCR-ABL1/ABL1≤10%）与12个月和24个月时更好的CCyR和MMR率相关（两组均如此）。胃肠道事件和肝功能检查指标升高在博舒替尼组更常见，而中性粒细胞减少、肌肉骨骼事件和水肿在博舒替尼组较少见。因不良事件停药在博舒替尼组比伊马替尼组更常见（最常见的是丙氨酸转氨酶升高：4%对<1%）；大多数发生在最初12个月内。两组的心血管不良事件相似。博舒替尼在新诊断的CP-CML患者中继续显示出良好的疗效和可管理的耐受性。
