Department of Hematology (K.S., H.M., X.C., D.Z., J.L.), Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
Department of Hematology, Changzheng Hospital, The Second Military Medical University, Shanghai, People's Republic of China (W.F.).
Circulation. 2022 Jan 4;145(1):8-17. doi: 10.1161/CIRCULATIONAHA.121.055953. Epub 2021 Sep 10.
Doxycycline was demonstrated in a retrospective study to be associated with greater survival in patients with light chain amyloidosis. Therefore, we prospectively compared the efficacy of bortezomib-cyclophosphamide-dexamethasone (CyBorD) and CyBorD combined with doxycycline for cardiac light chain amyloidosis.
This was a multicenter, open-label, randomized controlled trial. Patients with Mayo 2004 stage II to III light chain amyloidosis were included. Patients were randomized to doxycycline 100 mg twice daily along with 9 cycles of CyBorD (doxycycline group) or to 9 cycles of CyBorD alone (control group). The primary outcome was 2-year progression-free survival (PFS). PFS was defined as the time from randomization to death, hematologic progression, or organ progression (heart, kidney or liver). Hematologic progression was defined on the basis of a substantial increase in free light chain. An increase in either NT-proBNP (N-terminal pro B-type natriuretic peptide) or cardiac troponin was the main criterion for defining cardiac progression. Cardiac PFS, defined as the time from randomization to cardiac progression or death, was compared between groups in an exploratory analysis. The corresponding treatment hazard ratio was estimated with a Cox regression model.
One hundred forty patients underwent randomization, with 70 in each group. The median age was 61 years (range, 33-78 years) with a male:female ratio of 1.75:1. Stage II disease was present in 34 (48.6%) and 33 (47.1%) patients in the doxycycline and control groups, respectively. After a median follow-up duration of 24.4 months, 32 of 70 (45.7%) patients in the doxycycline group and 30 of 70 (42.9%) patients in the control group experienced progression. PFS was not significantly different between groups (hazard ratio, 0.97 [95% CI, 0.59-1.60]; =0.91). Cardiac progression occurred in 29 of 70 (41.4%) patients in the doxycycline group and 26 of 70 (37.1%) patients in the control group. The death rates for both groups by the end of follow-up was the same, 25 of 70 (35.7%). No significant differences were observed for either cardiac PFS (hazard ratio, 0.91 [95% CI, 0.54-1.55]; =0.74) or overall survival (hazard ratio, 1.04 [95% CI, 0.60-1.81]; =0.89).
Our trial demonstrated that doxycycline combined with CyBorD failed to prolong PFS or cardiac PFS compared with CyBorD alone in cardiac light chain amyloidosis. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03401372.
在一项回顾性研究中，多西环素被证明与轻链淀粉样变性患者的生存率提高有关。因此，我们前瞻性比较了硼替佐米-环磷酰胺-地塞米松（CyBorD）联合多西环素与 CyBorD 单独用于心脏轻链淀粉样变性的疗效。
这是一项多中心、开放标签、随机对照试验。纳入 Mayo 2004 分期 II 至 III 期轻链淀粉样变性患者。患者被随机分配至每日两次口服多西环素 100 mg 联合 9 个周期的 CyBorD（多西环素组）或 9 个周期的 CyBorD 单独治疗（对照组）。主要终点是 2 年无进展生存期（PFS）。PFS 定义为从随机分组到死亡、血液学进展或器官进展（心脏、肾脏或肝脏）的时间。血液学进展定义为游离轻链显著增加。N-末端脑钠肽前体（NT-proBNP）或心脏肌钙蛋白的增加是定义心脏进展的主要标准。从随机分组到心脏进展或死亡的心脏 PFS 在探索性分析中在组间进行比较。用 Cox 回归模型估计相应的治疗风险比。
140 例患者接受了随机分组，每组 70 例。中位年龄为 61 岁（范围 33-78 岁），男女比例为 1.75:1。多西环素组和对照组分别有 34 例（48.6%）和 33 例（47.1%）患者处于 II 期疾病。中位随访 24.4 个月后，多西环素组 70 例患者中有 32 例（45.7%）和对照组 70 例患者中有 30 例（42.9%）发生进展。两组 PFS 无显著差异（风险比，0.97[95%CI，0.59-1.60]；=0.91）。多西环素组 70 例患者中有 29 例（41.4%）和对照组 70 例患者中有 26 例（37.1%）发生心脏进展。两组在随访结束时的死亡率相同，均为 25 例（35.7%）。心脏 PFS（风险比，0.91[95%CI，0.54-1.55]；=0.74）或总生存期（风险比，1.04[95%CI，0.60-1.81]；=0.89）均无显著差异。
我们的试验表明，与 CyBorD 单独治疗相比，多西环素联合 CyBorD 并不能延长心脏轻链淀粉样变性患者的 PFS 或心脏 PFS。注册：网址：https://www.clinicaltrials.gov；唯一标识符：NCT03401372。
