Discordance between serum cardiac biomarker and immunoglobulin-free light-chain response in patients with immunoglobulin light-chain amyloidosis treated with immune modulatory drugs.
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.
Dispenzieri
Angela
A
Department of Medicine, Division of Hematology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. dispenzieri.angela@mayo.edu
Dingli
David
D
Kumar
Shaji K
SK
Rajkumar
S Vincent
SV
Lacy
Martha Q
MQ
Hayman
Suzanne
S
Buadi
Frances
F
Zeldenrust
Stephen
S
Leung
Nelson
N
Detweiler-Short
Kristen
K
Lust
John A
JA
Russell
Stephen J
SJ
Kyle
Robert A
RA
Gertz
Morie A
MA
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*
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