title: Carfilzomib and the cardiorenal system in myeloma: an endothelial effect?
abstract: Carfilzomib (Cfz) has been associated with an ~5% incidence of unexplained and unpredictable cardiovascular toxicity in clinical trials. We therefore implemented a detailed, prospective, clinical cardiac and renal evaluation of 62 Cfz-treated myeloma patients, including serial blood pressure (BP), creatinine, troponin, NT-proBNP and pre- and post-treatment echocardiograms, including ejection fraction (EF), average global longitudinal strain and compliance. Pre-treatment elevations in NT-proBNP and BP, as well as abnormal cardiac strain were common. A rise in NT-proBNP occurred frequently post-treatment often without corresponding cardiopulmonary symptoms. A rise in creatinine was common, lessened with hydration and often reversible. All patients had a normal EF pre-treatment. Five patients experienced a significant cardiac event (four decline in EF and one myocardial infarction), of which 2 (3.2%) were considered probably attributable to Cfz. None were rechallenged with Cfz. The ideal strategy for identifying patients at risk for cardiac events, and parameters by which to monitor for early toxicity have not been established; however, it appears baseline echocardiographic testing is not consistently predictive of toxicity. The toxicities observed suggest an endothelial mechanism and further clinical trials are needed to determine whether or not this represents a class effect or is Cfz specific.
authors.affiliation: Division of Hematology Oncology, Mayo Clinic Arizona, Scottsdale, AZ, USA.
authors.forename: A
authors.initials: A
authors.lastname: Rosenthal
authors.affiliation: Division of Hematology Oncology, Mayo Clinic Arizona, Scottsdale, AZ, USA.
authors.forename: J
authors.initials: J
authors.lastname: Luthi
authors.affiliation: Division of Hematology Oncology, Mayo Clinic Arizona, Scottsdale, AZ, USA.
authors.forename: M
authors.initials: M
authors.lastname: Belohlavek
authors.affiliation: Division of Hematology Oncology, Mayo Clinic Arizona, Scottsdale, AZ, USA.
authors.forename: K M
authors.initials: KM
authors.lastname: Kortüm
authors.affiliation: Division of Hematology Oncology, Mayo Clinic Arizona, Scottsdale, AZ, USA.
authors.forename: F
authors.initials: F
authors.lastname: Mookadam
authors.affiliation: Division of Hematology Oncology, Mayo Clinic Arizona, Scottsdale, AZ, USA.
authors.forename: A
authors.initials: A
authors.lastname: Mayo
authors.affiliation: Division of Hematology Oncology, Mayo Clinic Arizona, Scottsdale, AZ, USA.
authors.forename: R
authors.initials: R
authors.lastname: Fonseca
authors.affiliation: Division of Hematology Oncology, Mayo Clinic Arizona, Scottsdale, AZ, USA.
authors.forename: P L
authors.initials: PL
authors.lastname: Bergsagel
authors.affiliation: Division of Hematology Oncology, Mayo Clinic Arizona, Scottsdale, AZ, USA.
authors.forename: C B
authors.initials: CB
authors.lastname: Reeder
authors.affiliation: Division of Hematology Oncology, Mayo Clinic Arizona, Scottsdale, AZ, USA.
authors.forename: J R
authors.initials: JR
authors.lastname: Mikhael
authors.affiliation: Division of Hematology Oncology, Mayo Clinic Arizona, Scottsdale, AZ, USA.
authors.forename: A K
authors.initials: AK
authors.lastname: Stewart
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D015415:Biomarkers; D066126:Cardiotoxicity; D005260:Female; D006331:Heart Diseases / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D007674:Kidney Diseases / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000150:complications* / Q000188:drug therapy* / Q000473:pathology; D020097:Natriuretic Peptide, Brain; D009842:Oligopeptides / Q000494:pharmacology* / Q000627:therapeutic use*; D010446:Peptide Fragments; D061988:Proteasome Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D013318:Stroke Volume / Q000187:drug effects
chemical_list: D015415:Biomarkers; D009842:Oligopeptides; D010446:Peptide Fragments; D061988:Proteasome Inhibitors; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; C524865:carfilzomib