Adjuvant doxycycline to enhance anti-amyloid effects: Results from the dual phase 2 trial. EClinicalMedicine 2020 Jun;23:100361
Date
06/13/2020Pubmed ID
32529175Pubmed Central ID
PMC7280748DOI
10.1016/j.eclinm.2020.100361Scopus ID
2-s2.0-85085967990 (requires institutional sign-in at Scopus site) 25 CitationsAbstract
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.
Author List
D'Souza A, Szabo A, Flynn KE, Dhakal B, Chhabra S, Pasquini MC, Weihrauch D, Hari PNAuthors
Anita D'Souza MD Associate Professor in the Medicine department at Medical College of WisconsinBinod Dhakal MD Associate Professor in the Medicine department at Medical College of Wisconsin
Kathryn Eve Flynn PhD Vice Chair, Professor in the Medicine department at Medical College of Wisconsin
Parameswaran Hari MD Adjunct Professor in the Medicine department at Medical College of Wisconsin
Marcelo C. Pasquini MD, MS Professor in the Medicine department at Medical College of Wisconsin
Aniko Szabo PhD Professor in the Institute for Health and Equity department at Medical College of Wisconsin
Dorothee Weihrauch DVM, PhD Research Scientist II in the Anesthesiology department at Medical College of Wisconsin
