Bortezomib With or Without Dexamethasone in Primary Systemic (Light Chain) Amyloidosis
Bortezomib With or Without Dexamethasone in Primary Systemic (Light Chain) Amyloidosis
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DOI：
10.1200/jco.2009.23.8220
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发表时间：
2010-02-20
影响因子：
45.3
通讯作者：
Palladini, Giovanni
中科院分区：
文献类型：
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作者：
Kastritis, Efstathios;Wechalekar, Ashutosh D.;Palladini, Giovanni
PurposeTo评估硼替佐米联合或不联合地塞米松的疗效和耐受性，并确定用硼替佐米或联合治疗的原发性系统性轻链（AL）淀粉样变性患者的预后因素。19%的患者接受联合用药作为一线治疗，81%的患者既往接受过两次中位治疗，69%的患者患有难治性疾病，而大多数患者有症状的心脏受累或血清N末端脑钠肽前体（NT-proBNP）升高。结果血液学反应在中位数52天内达到71%，包括25%的完全反应（CR）。既往未接受治疗的患者CR率为47%。年龄小于等于65岁（P = 0.043）和每周两次硼替佐米给药（P = 0.041）与更高的反应率相关。在29%的患者中记录了心脏反应，大多数为功能等级的持续改善，较少为壁厚度的降低。血液学应答与心脏应答和NT-proBNP降低相关。中位随访12个月后，29%的患者发生器官进展，27%的患者发生血液学进展。中位生存期尚未达到，1年生存率为76%。基线NT-proBNP与生存率独立相关（P = .001），而在一项里程碑分析中，生存率与NT-proBNP降低>= 30%（P = .006）和血液学应答（P = .001）相关。毒性是可管理的，主要包括神经病变，体位性，外周水肿，便秘或diarrheum. ConclusionBortezelatin与或不与地塞米松是积极的AL淀粉样变性，并诱导快速反应和血液学和器官反应率高。心脏生物标志物的系列测量是预后的有力预测因素。
PurposeTo assess the efficacy and tolerability of bortezomib with or without dexamethasone and to define prognostic factors for patients with primary systemic light chain (AL) amyloidosis treated with bortezomib or both.Patients and MethodsNinety-four patients from three centers were analyzed: 19% received the combination as first-line treatment, 81% had a median of two previous therapies, and 69% had refractory disease, while most patients had symptomatic heart involvement or elevated serum N-terminal pro-brain natriuretic peptide (NT-proBNP).ResultsA hematologic response was achieved in 71% within a median of 52 days, including 25% complete responses (CRs). Previously untreated patients had a 47% CR rate. Age 65 years or younger (P = .043) and twice weekly administration of bortezomib (P = .041) were associated with higher response rates. A cardiac response was documented in 29% of patients, in most as sustained improvement of functional class and less often as a decrease in wall thickness. Hematologic responses were associated with a cardiac response and NT-proBNP reduction. After a median follow-up of 12 months, 29% of patients had organ progression and 27% had hematologic progression. Median survival has not been reached and the 1-year survival rate is 76%. Baseline NT-proBNP was independently associated with survival (P = .001), while in a landmark analysis, survival was associated with NT-proBNP reduction of >= 30% (P = .006) and achievement of hematologic response (P = .001). Toxicity was manageable and mostly consisted of neuropathy, orthostasis, peripheral edema, and constipation or diarrhea.ConclusionBortezomib with or without dexamethasone is active in AL amyloidosis and induces rapid responses and high rates of hematologic and organ responses. Serial measurement of cardiac biomarkers is a powerful predictor of outcome.