Li Jian’s team from the Department of Hematology of PUMCH published findings of their study, a multi-center, open-label randomized controlled trial, in the first issue of “Circulation” (IF=29.69) in 2022. The results showed that for light-chain (AL) cardiac amyloidosis, doxycycline combined with bortezomib/cyclophosphamide/dexamethasone (CyBorD), compared with CyBorD, did not prolong progression-free survival.
Patients with AL amyloidosis, which has always been an intractable disease, are marked by high early mortality and short survival. Some previous studies found that the antibiotic doxycycline can promote the degradation of amyloid deposition in the heart and improve the long-term survival of patients. Therefore, multiple guidelines and consensuses recommend it for the treatment of AL amyloidosis. However, the efficacy of doxycycline has not been validated by randomized controlled trials. Therefore, the Department of Hematology of PUMCH conducted a multicenter, open-label, randomized controlled trial to explore the efficacy difference between doxycycline combined with CyBorD chemotherapy and CyBorD chemotherapy for AL amyloidosis.
Patients with Mayo 2004 stage II to III light chain amyloidosis were included and they were subjected to stratified block randomization based on the Mayo stage. 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 endpoint was 2-year progression-free survival (PFS), which was defined as the time from randomization to hematologic progression, organ progression or death. Cardiac PFS (the time from randomization to cardiac progression or death) was compared between groups in an exploratory analysis.
One hundred and 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 group, 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. The death rates for both groups by the end of follow-up were the same, 25 of 70 (35.7%). No significant differences were observed for either cardiac PFS or overall survival.
The trial demonstrated that doxycycline combined with CyBorD failed to prolong PFS or cardiac PFS compared with CyBorD alone in cardiac light chain amyloidosis.
The Kaplan-Meier plot of the two groups showing PFS (left) and cardiac PFS (right)
Written by: The Department of Hematology
Picture courtesy: The Department of Hematology
Translator: Liu Haiyan
Editor: Zhao Danqing and Wang Yao