Iurlo Alessandra, Galimberti Sara, Abruzzese Elisabetta, Annunziata Mario, Bonifacio Massimiliano, Latagliata Roberto, Pregno Patrizia, Ferrero Dario, Sorà Federica, Orlandi Ester Maria, Fava Carmen, Cattaneo Daniele, Bucelli Cristina, Binotto Gianni, Pungolino Ester, Tiribelli Mario, Gozzini Antonella, Gugliotta Gabriele, Castagnetti Fausto, Stagno Fabio, Rege-Cambrin Giovanna, Martino Bruno, Luciano Luigiana, Breccia Massimo, Sica Simona, Bocchia Monica, Pane Fabrizio, Saglio Giuseppe, Rosti Gianantonio, Specchia Giorgina, Cortelezzi Agostino, Baccarani Michele
Hematology Division, IRCCS Ca' Granda - Maggiore Policlinico Hospital Foundation, University of Milan, Milan, Italy.
Department of Clinical and Experimental Medicine, Section of Hematology, University of Pisa, Pisa, Italy.
Ann Hematol. 2018 Jan;97(1):95-100. doi: 10.1007/s00277-017-3144-1. Epub 2017 Oct 2.
Pleural effusion (PE) represents the leading cause of dasatinib (DAS) discontinuation. However, the pathogenic mechanism of this adverse event (AE) is unknown and its management unclear. We investigated if a DAS dose reduction after the first PE would prevent the recurrence of this AE. We retrospectively collected data on all the cases of PE in CML-chronic phase (CP) DAS-treated patients from November 2005 to February 2017 in 21 Italian hematological centers. We identified 196 cases of PE in a series of 853 CML-CP DAS-treated patients (incidence 23.0%). DAS starting dose was 100 mg/day in 70.4% of patients, less than 100 mg/day in 14.3%, and more than 100 mg/day in the remaining cases. Median time from DAS start to PE was 16.6 months. At first PE development, 28.6% of patients were in MMR, and 37.8% in deep molecular response (DMR). DAS was temporary interrupted in 71.9% of cases, with a dose reduction in 59.2%. Recurrence was observed in 59.4% of the cases. Treatment was definitively discontinued due to PE in 29.1% of the cases. Interestingly, among patients whose DAS dosage was reduced, 59.5% experienced PE recurrence. DAS dose reduction after the first episode of PE did not prevent recurrence of this AE. Therefore, once a MMR or a DMR is achieved, different strategies of DAS dose management can be proposed prior to the development of PE, such as daily dose reduction or, as an alternative option, an on/off treatment with a weekend drug holiday.
胸腔积液（PE）是导致达沙替尼（DAS）停药的主要原因。然而，这一不良事件（AE）的致病机制尚不清楚，其处理方式也不明确。我们研究了首次发生PE后降低DAS剂量是否能预防该AE的复发。我们回顾性收集了2005年11月至2017年2月期间在意大利21家血液学中心接受DAS治疗的慢性期（CP）慢性粒细胞白血病（CML）患者中所有PE病例的数据。在一系列853例接受DAS治疗的CML-CP患者中，我们识别出196例PE病例（发生率为23.0%）。70.4%的患者DAS起始剂量为100mg/天，14.3%的患者低于100mg/天，其余患者高于100mg/天。从开始使用DAS到发生PE的中位时间为16.6个月。在首次发生PE时，28.6%的患者处于主要分子反应（MMR），37.8%的患者处于深度分子反应（DMR）。71.9%的病例中DAS被暂时中断，59.2%的病例进行了剂量降低。59.4%的病例观察到复发。29.1%的病例因PE最终停药。有趣的是，在DAS剂量降低的患者中，59.5%经历了PE复发。首次发生PE后降低DAS剂量并不能预防该AE的复发。因此，一旦达到MMR或DMR，可以在PE发生之前提出不同的DAS剂量管理策略，例如每日剂量降低，或者作为替代选择，采用周末停药的间断治疗。
