Long term follow-up of frontline Dasatinib in older patients with chronic myeloid leukemia in chronic phase treated outside clinical trials: a real-life cohort observational study

A limited amount of data has been published in chronic-phase chronic myeloid leukemia (CP-CML) patients aged >75 years treated frontline with second-generation tyrosine kinase inhibitors. To address this issue in a clinical ‘real-life’ setting, we retrospectively analyzed 45 CP-CML patients (pts) followed in 20 Italian Centers and treated frontline with dasatinib (DAS). Median age was 78.4 years (range 75–89.2 years). DAS starting dose was 100 mg QD in 35 pts (77.7%), 80 mg QD in 1 pts (2.2%) and 50 mg QD in 9 pts (20.1%), respectively. The median follow-up was 42.6 months (IQR 20.4 − 63.3). Grade 3 and 4 side effects, both hematological and non-hematological, were detected in 6 (13.3%) and 12 (26.6%) pts, respectively. Pleural effusions of all grades occurred in 13 pts (28.8%) after a median period of DAS exposure of 14.7 months (IQR 3.0 − 33.1). The rates of DAS dose reduction and permanent drug discontinuation were 53.3% and 20.0%, respectively. As the best response, 42/45 patients (93.3%) achieved a complete cytogenetic response (CCyR), 35/45 (77.7%) a major molecular response (MMR) and 24/45 (53.3%) a deep molecular response (both MR 4.0 and MR 4.5). Only 1 patient (2.2%) progressed to the blast phase after 13 months of therapy; 8 deaths were observed (1 CML-related and 7 CML-unrelated). Cumulative event-free survival and overall survival at 36 months were 64.7% (95%, CI 49.4 − 80.0) and 82.3% (95%, CI 70.3–94.3), respectively. These findings, although evaluated in a limited and selected cohort of patients, suggest that DAS might be effective in older patients (aged >75 years) affected by CP-CML with acceptable toxicity.

目前针对采用第二代酪氨酸激酶抑制剂一线治疗的75岁以上慢性髓系白血病慢性期（chronic-phase chronic myeloid leukemia, CP-CML）患者，已发表的相关数据较为有限。为解决真实世界临床场景中的这一数据缺口，本研究回顾性分析了来自20个意大利医疗中心的45例CP-CML患者（pts，患者）的病例资料，所有患者均采用达沙替尼（dasatinib, DAS）一线治疗。患者中位年龄为78.4岁，年龄区间为75~89.2岁。达沙替尼的初始给药剂量分别为100mg每日一次（quaque die, QD）、80mg QD及50mg QD，对应患者例数分别为35例（77.7%）、1例（2.2%）与9例（20.1%）。中位随访时间为42.6个月，四分位距（interquartile range, IQR）为20.4~63.3个月。共6例（13.3%）患者发生3级不良反应，12例（26.6%）发生4级不良反应，不良反应类型涵盖血液学与非血液学两类。所有级别胸腔积液共发生于13例患者（28.8%），患者接受达沙替尼治疗至出现胸腔积液的中位时间为14.7个月，四分位距为3.0~33.1个月。达沙替尼剂量减量与永久停药的发生率分别为53.3%与20.0%。就最佳治疗反应而言，42/45例患者（93.3%）达到完全细胞遗传学缓解（complete cytogenetic response, CCyR），35/45例（77.7%）达到主要分子学缓解（major molecular response, MMR），24/45例（53.3%）达到深层分子学缓解（涵盖MR 4.0与MR 4.5两种等级）。仅1例患者（2.2%）在接受治疗13个月后进展为急变期；共计发生8例死亡事件，其中1例与慢性髓系白血病相关，7例与慢性髓系白血病无关。36个月时的累计无事件生存期与总生存期分别为64.7%（95%置信区间，confidence interval, CI：49.4~80.0）与82.3%（95%CI：70.3~94.3）。尽管本研究的患者队列规模有限且经过筛选，但上述研究结果表明，达沙替尼用于治疗75岁以上CP-CML患者时，可获得较好的治疗效果，且毒性反应可接受。