title: Endothelial stress products and coagulation markers in patients with multiple myeloma treated with lenalidomide plus dexamethasone: an observational study.
abstract: In this prospective study of patients with relapsed or relapsed and refractory multiple myeloma (MM) treated with lenalidomide and dexamethasone, relationships between markers of endothelial stress and drug administration and incidence of venous thromboembolism (VTE) were assessed. Of 33 enrolled patients, laboratory and treatment data were available for 32 patients. Of these, 23 received pulsed dexamethasone (40 mg/day on days 1-4, 9-12 and 17-21 of each 28-day cycle) and 9 received weekly dexamethasone (40 mg/day on days 1, 8, 15 and 21 of each cycle). The overall incidence of VTE was 9%. A decreasing trend in markers values was observed with intercellular adhesion molecule (P = 0·05), fibrinogen (P = 0·008), plasminogen activator inhibitor-1 (P < 0·001), homocysteine (P = 0·002) and P-selectin (P < 0·001) during therapy. Compared with weekly dexamethasone, pulsed dexamethasone was associated with significantly greater variation in mean adjusted relative values of fibrinogen, P-selectin and vascular endothelial growth factor (P < 0·001 for all comparisons), although there was no apparent association with VTE incidence. Lenalidomide plus dexamethasone affects endothelial stress marker levels in patients with advanced MM. The higher variation seen with pulsed dexamethasone suggests greater endothelial stress with this approach.
authors.affiliation: Medical Oncology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA. rprosovsky@partners.org
authors.forename: Rachel
authors.initials: R
authors.lastname: Rosovsky
authors.forename: Fangxin
authors.initials: F
authors.lastname: Hong
authors.forename: Deanna
authors.initials: D
authors.lastname: Tocco
authors.forename: Brendan
authors.initials: B
authors.lastname: Connell
authors.forename: Constantine
authors.initials: C
authors.lastname: Mitsiades
authors.forename: Robert
authors.initials: R
authors.lastname: Schlossman
authors.forename: Irene
authors.initials: I
authors.lastname: Ghobrial
authors.forename: Leslie
authors.initials: L
authors.lastname: Lockridge
authors.forename: Diane
authors.initials: D
authors.lastname: Warren
authors.forename: Gary
authors.initials: G
authors.lastname: Bradwin
authors.forename: Mary
authors.initials: M
authors.lastname: Doyle
authors.forename: Nikhil
authors.initials: N
authors.lastname: Munshi
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Soiffer
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Anderson
authors.forename: Edie
authors.initials: E
authors.lastname: Weller
authors.forename: Paul
authors.initials: P
authors.lastname: Richardson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D001777:Blood Coagulation; D001779:Blood Coagulation Factors / Q000378:metabolism*; D016000:Cluster Analysis; D003907:Dexamethasone / Q000008:administration & dosage; D042783:Endothelial Cells / Q000378:metabolism*; D005260:Female; D006801:Humans; D015994:Incidence; D000077269:Lenalidomide; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism*; D011446:Prospective Studies; D013312:Stress, Physiological; D013792:Thalidomide / Q000008:administration & dosage / Q000031:analogs & derivatives; D054556:Venous Thromboembolism / Q000453:epidemiology / Q000209:etiology
chemical_list: D015415:Biomarkers; D001779:Blood Coagulation Factors; D013792:Thalidomide; D003907:Dexamethasone; D000077269:Lenalidomide