艾曲泊帕治疗成人原发免疫性血小板减少症停药后疗效维持及预测因素

Maintenance of efficacy and its predictors after discontinuation of eltrombopag in adults with primary immune thrombocytopenia

目的观察艾曲泊帕对成人原发免疫性血小板减少症(ITP)的治疗反应和停药后疗效维持情况并探寻其预测因素。方法纳入2013年6月14日至2021年5月31日期间在上海交通大学医学院附属瑞金医院血液科接受艾曲泊帕治疗的成人ITP患者,对其临床资料进行回顾性分析。随访截止时间为2021年12月31日。艾曲泊帕起始剂量为25 mg/d口服,最大剂量75 mg/d。按照血小板计数调整艾曲泊帕剂量,维持血小板计数(50~150)×10^(9)/L。基于患者意愿和医生判断(处方用药)或者临床试验按照方案终止用药。对所有接受艾曲泊帕治疗的患者进行疗效评估,在治疗有效(疗效评估为完全反应或有效)并且减停艾曲泊帕的患者中进行无治疗有效(TFR)评估,对相关因素进行分析。结果106例ITP患者纳入研究,男33例,女73例,中位年龄50(18~89)岁;新诊断ITP 2例,持续性ITP 10例,慢性ITP 94例。艾曲泊帕治疗后完全反应率为44.3%(47/106),有效率为34.0%(36/106),总反应率(ORR)为78.3%(83/106)。83例治疗有效患者经过艾曲泊帕停药,81例可评估停药后疗效,17例(21.0%)获得TFR。获得TFR的患者中位随访时间126(30~170)周,复发率为17.6%(3/17),无复发生存率(RFS)为76.5%。单因素分析结果显示,停止其他ITP合并治疗后无复发(P=0.001)、艾曲泊帕开始减停时血小板计数≥100×10^(9)/L(P=0.007)、艾曲波帕开始减停时剂量≤25 mg/d(P=0.031)与有效持续时间延长相关。多因素分析结果显示,停止其他ITP合并治疗后无复发与有效持续时间延长相关(P=0.002)。结论艾曲泊帕对成人ITP患者有效且部分患者可获得TFR。停止其他ITP合并治疗后无复发、艾曲泊帕开始减停时PLT≥100×10^(9)/L以及艾曲泊帕开始减停时剂量≤25 mg/d是获得TFR的预测因素。

Objective To determine the efficacy of eltrombopag for primary immune thrombocytopenia(ITP)in adults and the predictive factors for treatment-free response(TFR).Methods Clinical data of adults with ITP who received eltrombopag from June 14,2013 to May 31,2021 in the Hematology Department of Ruijin Hospital affiliated with Shanghai Jiao Tong University Medical College were retrospectively analyzed.The initial dose of eltrombopag was 25 mg/d,and the maximum dose was 75 mg/d;the dose was adjusted to maintain the platelet count to within 50-150×10^(9)/L.Treatment was discontinued according either to the protocol,on the patient’s wishes or doctor’s judgment(prescription medication),or based on clinical trials.The efficacy of eltrombopag and factors for TFR among patients who achieved complete response and those who discontinued treatment were analyzed.Results Overall,106 patients with ITP(33 men and 73 women)were included in the study.The median age of patients was 50(18-89)years.There were 2,10,and 94 cases of newly diagnosed,persistent,and chronic ITP,respectively.The complete response rate was 44.3%(47/106),the response rate was 34.0%(36/106),and the overall response rate was 78.3%(83/106).Meanwhile,83 patients who responded to treatment discontinued eltrombopag;of these,81 patients were evaluated.Additionally,17 patients(21.0%)achieved TFR.The median follow-up duration of patients who achieved TFR was 126(30-170)weeks.The recurrence rate was 17.6%(3/17),and the relapse-free survival rate was 76.5%.The results of univariate analysis revealed that non-recurrence after discontinuation of other treatments for ITP(P=0.001),and platelet count and eltrombopag dose of≥100×10^(9)/L(P=0.007)and≤25 mg/d(P=0.031),respectively,upon discontinuation of eltrombopag were predictors of TFR;these effects were attributed to prolonged effective duration of eltrombopag.Multivariate analysis showed that there was a correlation between non-recurrence and prolonged effective duration after discontinuation of other treatments for ITP(P=0.002).Conclusion Eltrombopag is effective for patients with ITP as it can result in TFR.Predictors for TFR include non-recurrence after discontinuation of concomitant ITP treatment,and platelet count and eltrombopag dose of≥100×10^(9)/L and≤25 mg/d upon discontinuation of treatment,respectively.