Oral melphalan and dexamethasone grants extended survival with minimal toxicity in AL amyloidosis: long-term results of a risk-adapted approach
Oral melphalan and dexamethasone grants extended survival with minimal toxicity in AL amyloidosis: long-term results of a risk-adapted approach
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DOI：
10.3324/haematol.2013.095463
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发表时间：
2014-04-01
期刊：
影响因子：
10.1
通讯作者：
Merlini, Giampaolo
中科院分区：
文献类型：
--
作者：
Palladini, Giovanni;Milani, Paolo;Merlini, Giampaolo
口服美法仑和地塞米松的组合被认为是不适合自体干细胞移植的轻链淀粉样变性患者的标准治疗。然而，以前的试验报告了不同的反应率和生存率，主要是因为高危患者的比例不同。在本研究中，共纳入259例受试者，我们用全剂量美法仑和地塞米松（地塞米松40 mg，第1-4天）治疗了119例患者，用减毒地塞米松方案（20 mg）治疗了140例晚期心脏病患者。全剂量组的血液学缓解率为76%，接受减毒方案的患者为51%;相应的完全缓解率分别为31%和12%。全剂量组的中位生存期为7.4年，减剂量组为20个月。使用大剂量地塞米松、氨基末端B型利钠肽前体>1800 ng/L、受累和未受累游离轻链之间的差异>180 mg/L、肌钙蛋白I >0.07 ng/mL和对治疗的反应是独立的预后决定因素。在复发性/难治性受试者中，硼替佐米联合给药获得了较高的血液学缓解率（分别为79%和63%），证明是继美法仑和地塞米松之后最有效的补救治疗。总之，美法仑加地塞米松是高度有效的，毒性最小，证实了其在治疗AL淀粉样变性中的核心作用。未来的随机试验将阐明硼替佐米是否最好用于与美法仑和地塞米松的一线联合治疗或作为补救治疗。
The combination of oral melphalan and dexamethasone is considered standard therapy for patients with light-chain amyloidosis ineligible for autologous stem cell transplantation. However, previous trials reported different rates of response and survival, mainly because of the different proportions of high-risk patients. In the present study, including a total of 259 subjects, we treated 119 patients with full-dose melphalan and dexamethasone (dexamethasone 40 mg days 1-4), and 140 patients with advanced cardiac disease with an attenuated dexamethasone schedule (20 mg). Hematologic response rates were 76% in the full-dose group and 51% in the patients receiving the attenuated schedule; the corresponding complete response rates were 31% and 12%, respectively. The median survival was 7.4 years in the full-dose group and 20 months in the attenuated-dose group. Use of high-dose dexamethasone, amino-terminal pro-natriuretic peptide type-B >1800 ng/L, a difference between involved and uninvolved free light chains of >180 mg/L, troponin I >0.07 ng/mL, and response to therapy were independent prognostic determinants. In relapsed/refractory subjects bortezomib combinations granted high hematologic response rates (79% and 63%, respectively), proving the most effective rescue treatment after melphalan and dexamethasone. In summary, melphalan plus dexamethasone was highly effective with minimal toxicity, confirming its central role in the treatment of AL amyloidosis. Future randomized trials will clarify whether bortezomib is best used in frontline combination with melphalan and dexamethasone or as rescue treatment.