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D'Souza A, Szabo A, Flynn KE, et al. Adjuvant doxycycline to enhance anti-amyloid effects: Results from the dual phase 2 trial. EClinicalMedicine. 2020;23:100361doi: 10.1016/j.eclinm.2020.100361.
D'Souza, A., Szabo, A., Flynn, K. E., Dhakal, B., Chhabra, S., Pasquini, M. C., Weihrauch, D., & Hari, P. N. (2020). Adjuvant doxycycline to enhance anti-amyloid effects: Results from the dual phase 2 trial. EClinicalMedicine, 23100361. https://doi.org/10.1016/j.eclinm.2020.100361
D'Souza, Anita, et al. "Adjuvant doxycycline to enhance anti-amyloid effects: Results from the dual phase 2 trial." EClinicalMedicine vol. 23 (2020): 100361. doi: https://doi.org/10.1016/j.eclinm.2020.100361
D'Souza A, Szabo A, Flynn KE, Dhakal B, Chhabra S, Pasquini MC, Weihrauch D, Hari PN. Adjuvant doxycycline to enhance anti-amyloid effects: Results from the dual phase 2 trial. EClinicalMedicine. 2020 Jun 05;23:100361. doi: 10.1016/j.eclinm.2020.100361. eCollection 2020 Jun. PMID: 32529175; PMCID: PMC7280748.
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EClinicalMedicine. 2020 Jun 05;23:100361. doi: 10.1016/j.eclinm.2020.100361. eCollection 2020 Jun.

Adjuvant doxycycline to enhance anti-amyloid effects: Results from the dual phase 2 trial.

EClinicalMedicine

Anita D'Souza, Aniko Szabo, Kathryn E Flynn, Binod Dhakal, Saurabh Chhabra, Marcelo C Pasquini, Dorothee Weihrauch, Parameswaran N Hari

Affiliations

  1. Division of Hematology/Oncology, Department of Medicine, United States.
  2. Division of Biostatistics, Institute of Health and Safety, United States.
  3. Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, WI 53226, United States.

PMID: 32529175 PMCID: PMC7280748 DOI: 10.1016/j.eclinm.2020.100361

Abstract

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.

© 2020 The Author(s).

Keywords: Doxycycline; Early mortality; Systemic light chain amyloidosis

Conflict of interest statement

AD- Grant funding and honoraria- Sanofi, EDO Mundipharma, TeneoBio, Takeda, Prothena, Pfizer, Imbrium, Akcea BD- Grant funding and Honoria- Takeda, Celgene, Janssen, Amgen and GSK PH- Grant funding an

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