Palladini Giovanni, Milani Paolo, Foli Andrea, Obici Laura, Lavatelli Francesca, Nuvolone Mario, Caccialanza Riccardo, Perlini Stefano, Merlini Giampaolo
Haematologica. 2014 Apr;99(4):743-50. doi: 10.3324/haematol.2013.095463. Epub 2013 Nov 8.
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.
对于不适合进行自体干细胞移植的轻链淀粉样变性患者，口服美法仑和地塞米松联合治疗被视为标准疗法。然而，既往试验报道的缓解率和生存率有所不同，主要是因为高危患者的比例不同。在本研究中，共纳入259名受试者，我们对119例患者采用全剂量美法仑和地塞米松治疗（地塞米松40mg，第1 - 4天），对140例患有晚期心脏病的患者采用减量地塞米松方案（20mg）。全剂量组的血液学缓解率为76%，接受减量方案的患者为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，减量组为20个月。使用高剂量地塞米松、氨基末端B型利钠肽>1800ng/L、受累与未受累游离轻链差值>180mg/L、肌钙蛋白I>0.07ng/mL以及对治疗的反应是独立的预后决定因素。在复发/难治性受试者中，硼替佐米联合方案获得了较高的血液学缓解率（分别为79%和63%），证明是美法仑和地塞米松治疗后最有效的挽救治疗方法。总之，美法仑加地塞米松疗效显著且毒性极小，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最适合与美法仑和地塞米松联合用于一线治疗还是作为挽救治疗。
