title: Discordance between serum cardiac biomarker and immunoglobulin-free light-chain response in patients with immunoglobulin light-chain amyloidosis treated with immune modulatory drugs.
abstract: We evaluated the capability of soluble cardiac biomarkers to predict tolerability and outcomes of IMiD-containing treatments among 106 patients treated on clinical trials. Baseline elevations in troponin T (TnT) and N-terminal brain naturietic protein (NT-proBNP) predicted for an inability to tolerate IMiD-based regimens. The best predictors for early attrition during cycle 1 were TnT ≥ 0.07 μg/L and NT-proBNP ≥ 11,939 ng/L. NT-proBNP-response underperformed TnT-response as a predictor for overall survival (OS), but both predicted for early protocol attrition. Despite hematologic response, IMiD-treated patients were at higher risk for NT-proBNP rises and early drug discontinuation than a control population but not for early death. These observations prompt two questions: (1) does IMiD-based therapy lead to increased fluid retention and/or cardiac toxicity and (2) is an NT-proBNP-driven cardiac response system valid in IMiD-treated amyloidosis patients? Recognition of potential drug-induced cardiac toxicity is important so that increased cardiac surveillance and drug dose-adjustment or discontinuation may be implemented.
authors.affiliation: Department of Medicine, Division of Hematology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. dispenzieri.angela@mayo.edu
authors.forename: Angela
authors.initials: A
authors.lastname: Dispenzieri
authors.forename: David
authors.initials: D
authors.lastname: Dingli
authors.forename: Shaji K
authors.initials: SK
authors.lastname: Kumar
authors.forename: S Vincent
authors.initials: SV
authors.lastname: Rajkumar
authors.forename: Martha Q
authors.initials: MQ
authors.lastname: Lacy
authors.forename: Suzanne
authors.initials: S
authors.lastname: Hayman
authors.forename: Frances
authors.initials: F
authors.lastname: Buadi
authors.forename: Stephen
authors.initials: S
authors.lastname: Zeldenrust
authors.forename: Nelson
authors.initials: N
authors.lastname: Leung
authors.forename: Kristen
authors.initials: K
authors.lastname: Detweiler-Short
authors.forename: John A
authors.initials: JA
authors.lastname: Lust
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Russell
authors.forename: Robert A
authors.initials: RA
authors.lastname: Kyle
authors.forename: Morie A
authors.initials: MA
authors.lastname: Gertz
mesh_terms: D000682:Amyloid / Q000097:blood*; D000686:Amyloidosis / Q000097:blood / Q000150:complications / Q000628:therapy*; D015415:Biomarkers; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D003907:Dexamethasone / Q000009:adverse effects / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D006333:Heart Failure / Q000097:blood / Q000139:chemically induced* / Q000209:etiology; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000097:blood*; D007155:Immunologic Factors / Q000009:adverse effects* / Q000627:therapeutic use; D000077269:Lenalidomide; D008558:Melphalan / Q000009:adverse effects / Q000627:therapeutic use; D020097:Natriuretic Peptide, Brain / Q000032:analysis*; D010352:Patient Dropouts; D010446:Peptide Fragments / Q000032:analysis*; D033581:Stem Cell Transplantation; D013792:Thalidomide / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D020107:Troponin T / Q000097:blood*
chemical_list: D000682:Amyloid; D015415:Biomarkers; D007147:Immunoglobulin Light Chains; D007155:Immunologic Factors; D010446:Peptide Fragments; D020107:Troponin T; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D013792:Thalidomide; D003907:Dexamethasone; D003520:Cyclophosphamide; C467566:pomalidomide; D000077269:Lenalidomide; D008558:Melphalan