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Background: 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., Methods: 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., Results: 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]; P =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]; P =0.74) or overall survival (hazard ratio, 1.04 [95% CI, 0.60-1.81]; P =0.89)., Conclusions: 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.

Relapsed and refractory (R/R) idiopathic Multicentric Castleman disease (iMCD) is a clinical challenge with few treatment options. In this first multicenter, prospective trial which implemented the recently published CDCN response criteria, we evaluated the efficacy and safety profiles of bortezomib-cyclophosphamide-dexamethasone (BCD) regimen in 24 R/R iMCD patients. By 6 months, 15 patients (62.5%) achieved overall treatment responses; four patients (16.7%) had stable disease and five patients (20.8%) suffered from progression of disease. Even when considering all patients, there were significant (p <.05) improvements in median symptom score, hemoglobin, platelet count, C-reactive protein (CRP) erythrocyte sedimentation rate (ESR), IL-6, albumin, and immunoglobin G (IgG) after treatment. The regimen was well tolerated without grade 3 or higher adverse events. Estimated 1-year progression-free survival (PFS) and overall survival (OS) were 79% and 92%, respectively. BCD regimen is an effective and safe treatment option for R/R iMCD patients. This trial was registered at as # ChiCTR1800019342. [ABSTRACT FROM AUTHOR]