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.
© 2010 Wiley-Liss, Inc.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Amyloid / blood*
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Amyloidosis / blood
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Amyloidosis / complications
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Amyloidosis / therapy*
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Biomarkers
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Clinical Trials as Topic / statistics & numerical data
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Combined Modality Therapy
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Cyclophosphamide / administration & dosage
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Cyclophosphamide / adverse effects
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Dexamethasone / adverse effects
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Dexamethasone / therapeutic use
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Drug Therapy, Combination
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Heart Failure / blood
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Heart Failure / chemically induced*
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Heart Failure / etiology
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Humans
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Immunoglobulin Light Chains / blood*
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Immunologic Factors / adverse effects*
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Immunologic Factors / therapeutic use
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Lenalidomide
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Melphalan / adverse effects
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Melphalan / therapeutic use
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Natriuretic Peptide, Brain / analysis*
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Patient Dropouts
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Peptide Fragments / analysis*
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Stem Cell Transplantation
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Thalidomide / adverse effects
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Thalidomide / analogs & derivatives
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Thalidomide / therapeutic use
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Troponin T / blood*
Substances
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Amyloid
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Biomarkers
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Immunoglobulin Light Chains
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Immunologic Factors
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Peptide Fragments
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Troponin T
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pro-brain natriuretic peptide (1-76)
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Natriuretic Peptide, Brain
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Thalidomide
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Dexamethasone
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Cyclophosphamide
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pomalidomide
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Lenalidomide
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Melphalan