title: Thalidomide-prednisone maintenance following autologous stem cell transplant for multiple myeloma: effect on thrombin generation and procoagulant markers in NCIC CTG MY.10.
abstract: Venous thromboembolism (VTE) has an increased incidence in patients with multiple myeloma (MM), especially during chemotherapy. Mechanisms including upregulation of procoagulant factors, such as factor VIII, have been postulated. The National Cancer Institute of Canada Clinical Trials Group MY.10 phase III clinical trial compared thalidomide-prednisone to observation for 332 patients with MM post-autologous stem cell transplantation (ASCT), with a primary endpoint of overall survival and various secondary endpoints including the incidence of VTE. One hundred and fifty-three patients had biomarker data, including D-dimer, factor VIII and thrombin anti-thrombin (TAT) levels collected post-ASCT at baseline and 2 months after intervention investigating in-vivo thrombin generation. Differences between the time-points included a significant reduction over time in D-dimer, factor VIII and TAT levels in the observation group and sustained elevation of D-dimer, significant increase in factor VIII and reduction in TAT levels in the thalidomide-prednisone group. Eight VTE events were reported in this subset of study patients, all in the thalidomide-prednisone arm, with a trend to increase in D-dimer levels over time in those patients with VTE. This study provides physiological and clinical evidence for an increased risk of VTE associated with thalidomide-prednisone maintenance therapy post-ASCT for MM.
authors.affiliation: London Health Sciences Centre, London, ON, Canada.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Kovacs
authors.forename: Gwynivere A
authors.initials: GA
authors.lastname: Davies
authors.forename: Judy-Anne W
authors.initials: JA
authors.lastname: Chapman
authors.forename: Nizar
authors.initials: N
authors.lastname: Bahlis
authors.forename: Michael
authors.initials: M
authors.lastname: Voralia
authors.forename: Jean
authors.initials: J
authors.lastname: Roy
authors.forename: C Tom
authors.initials: CT
authors.lastname: Kouroukis
authors.forename: Christine
authors.initials: C
authors.lastname: Chen
authors.forename: Andrew
authors.initials: A
authors.lastname: Belch
authors.forename: Donna
authors.initials: D
authors.lastname: Reece
authors.forename: Liting
authors.initials: L
authors.lastname: Zhu
authors.forename: Ralph M
authors.initials: RM
authors.lastname: Meyer
authors.forename: Lois
authors.initials: L
authors.lastname: Shepherd
authors.forename: Keith A
authors.initials: KA
authors.lastname: Stewart
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000990:Antithrombin III / Q000032:analysis*; D003131:Combined Modality Therapy; D005169:Factor VIII / Q000032:analysis*; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis*; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D060046:Maintenance Chemotherapy; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood / Q000188:drug therapy / Q000628:therapy*; D010447:Peptide Hydrolases / Q000032:analysis*; D011241:Prednisone / Q000008:administration & dosage; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects; D013917:Thrombin / Q000096:biosynthesis*; D019851:Thrombophilia / Q000097:blood / Q000139:chemically induced*; D014182:Transplantation, Autologous; D054556:Venous Thromboembolism / Q000453:epidemiology / Q000517:prevention & control
chemical_list: D005338:Fibrin Fibrinogen Degradation Products; C046193:antithrombin III-protease complex; C036309:fibrin fragment D; D013792:Thalidomide; C078147:F8 protein, human; D000990:Antithrombin III; D005169:Factor VIII; D010447:Peptide Hydrolases; D013917:Thrombin; D011241:Prednisone
keywords: autologous transplantation; biomarkers; myeloma; thalidomide; venous thromboembolism