Nicolini Franck Emmanuel, Alcazer Vincent, Cony-Makhoul Pascale, Heiblig Maël, Morisset Stéphane, Fossard Gaëlle, Bidet Audrey, Schmitt Anna, Sobh Mohamad, Hayette Sandrine, Mahon François-Xavier, Dulucq Stéphanie, Etienne Gabriel
Hematology Department, Centre Léon Bérard, Lyon, France; INSERM U1052, Centre de Recherche en Cancérologie de Lyon, Centre Léon Bérard, Lyon, France; Groupe Fi-LMC, Institut Bergonié, Bodeaux, France.
Hematology Department, Centre Léon Bérard, Lyon, France.
Exp Hematol. 2018 Aug;64:97-105.e4. doi: 10.1016/j.exphem.2018.05.003. Epub 2018 May 23.
For the last 15years, imatinib mesylate (IM) has represented the gold standard treatment for chronic-phase chronic myelogenous leukemia (CP-CML); however, outcomes in the very long term remain unknown. We retrospectively analyzed the outcome of 418 IM first-line treated CP-CML patients followed in three reference centers over 15years in and outside of clinical trials, which is believed to represent the "real-life" care of such patients. Molecular analyses were standardized over the years. In case of intolerance or resistance or IM cessation and progression, all clinical data were collected and analyzed. After a median follow-up of 83 months (range 1-194), the overall survival (OS) rates were 91% and 82%, the progression-free survival (PFS) rates were 88.5% and 81%, and the event-free survival rates, including switching to another tyrosine kinase inhibitor, were 65% and 51%, respectively, at 5 and 10years. Thirteen patients (3%) entered blast crisis (BC) with a median survival of 2.2years after BC onset. Forty-nine percent of patients were in major molecular response at 1 year. Univariate analysis failed to detect any impact on survival of molecular response at 3 and 6 months. Sokal score had a significant impact on OS and PFS in a Cox model. Age had a significant impact on OS and PFS, mainly due to deaths in elderly patients unrelated to CML. Overall, 21% of patients reached a stable (≥1 year) molecular response 4 (MR4) and 6.5% reached MR4.5. At last follow-up, 63% of patients were still on IM and 19% were in treatment-free remission. We conclude that IM is an excellent therapeutic option providing impressive long-term OS rates.
在过去的15年里，甲磺酸伊马替尼（IM）一直是慢性期慢性髓性白血病（CP-CML）的金标准治疗药物；然而，其长期疗效仍不明确。我们回顾性分析了在三个参考中心接受IM一线治疗的418例CP-CML患者在15年期间（包括临床试验内外）的治疗结果，这被认为代表了此类患者的“真实生活”治疗情况。多年来分子分析已标准化。对于不耐受、耐药、IM停药或病情进展的情况，收集并分析所有临床数据。中位随访83个月（范围1-194个月）后，5年和10年时的总生存率（OS）分别为91%和82%，无进展生存率（PFS）分别为88.5%和81%，包括改用另一种酪氨酸激酶抑制剂的无事件生存率分别为65%和51%。13例患者（3%）进入急变期（BC），BC期发病后的中位生存期为2.2年。49%的患者在1年时达到主要分子反应。单因素分析未发现3个月和6个月时的分子反应对生存有任何影响。在Cox模型中，Sokal评分对OS和PFS有显著影响。年龄对OS和PFS有显著影响，主要是由于老年患者中与CML无关的死亡。总体而言，21%的患者达到稳定（≥1年）分子反应4（MR4），6.5%的患者达到MR4.5。在最后一次随访时，63%的患者仍在使用IM，19%的患者处于无治疗缓解状态。我们得出结论，IM是一种出色的治疗选择，可提供令人印象深刻的长期OS率。
