Adjuvant doxycycline to enhance anti-amyloid effects: Results from the dual phase 2 trial
Adjuvant doxycycline to enhance anti-amyloid effects: Results from the dual phase 2 trial
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DOI：
10.1016/j.eclinm.2020.100361
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发表时间：
2020-06-01
影响因子：
15.1
通讯作者：
Hari, Parameswaran N.
中科院分区：
文献类型：
--
作者：
D'Souza, Anita;Szabo, Aniko;Hari, Parameswaran N.
背景：虽然在回顾性研究中，强力霉素的使用与淀粉样变性的预后改善有关，但临床试验的证据有限。方法：该多西环素（clinicaltrials.gov: NCT02207556）治疗新诊断为轻链（AL）淀粉样变性的2期试验纳入了25例系统性AL淀粉样变性患者，他们接受多西环素治疗1年并进行化疗。研究结果包括1年死亡率、器官反应和血液学反应率。结果：中位年龄为62岁，64%为男性，68%为AL lambda亚型。24%的患者进入Mayo 2012期3期，28%的患者进入4期。60%的患者有心脏受累，72%的患者有肾脏受累，60%的患者有3个或更多器官受累。靶器官为心脏14例（56%），肾脏7例（28%），肝脏1例（4%），软组织3例（12%）。1年死亡率为20%(95%可信区间，8.9-41.6%)，器官反应为36%（18-57%）。1年幸存者的血液学反应为100%，包括30%完全缓解和55%非常好的部分缓解。自体造血细胞移植占60%；在移植患者中，100天的移植相关死亡率为0。强力霉素的使用是安全的，没有任何2级或更高的毒性。解释：除了低1年死亡率外，强力霉素的使用是安全的，并且与高移植利用率相关。因此，我们认为应该在第一年新诊断的AL患者中进行多西环素的安慰剂对照研究，特别是在疾病晚期和心脏受累的患者中。(C) 2020作者。Elsevier Ltd.出版。
Background: Although, doxycycline use is associated with improved outcomes in amyloidosis in retrospective studies, evidence from clinical trials is limited.Methods: This phase 2 trial of doxycycline (clinicaltrials.gov: NCT02207556) in newly diagnosed light chain (AL) amyloidosis enrolled 25 patients with systemic AL amyloidosis on treatment with doxycycline for 1 year along with chemotherapy. Outcomes of interest included mortality, organ response, and hematologic response rates at 1 year.Findings: The median age was 62 years, 64% were male, and 68% had the AL lambda subtype. Patients had Mayo 2012 stage 3 in 24% and stage 4 in 28%. Cardiac involvement was present in 60% of patients, renal involvement in 72%, and 60% patients had 3 or more organs involved. Target organ was cardiac in 14(56%), renal in 7(28%), hepatic in 1(4%) and soft tissue in 3(12%). At 1 year, mortality was 20% (95% confidence interval, 8.9-41.6%) and organ response was 36% (18-57%). Hematologic response in 1-year survivors was 100%, including 30% complete and 55% very good partial response. Autologous hematopoietic cell transplant was performed in 60%; among transplanted patients, day-100 transplant-related mortality was 0. Doxycycline use was safe and not attributed to any grade 2 or higher toxicity.Interpretation: In addition to a low 1-year mortality, doxycycline use was safe and associated with high transplant utilization rate. We thus contend that doxycycline should be studied in a placebo-controlled study in newly diagnosed AL patients in the first year, particularly among patients with advanced disease and cardiac involvement. (C) 2020 The Author(s). Published by Elsevier Ltd.