title: Risk factors and kinetics of thrombocytopenia associated with bortezomib for relapsed, refractory multiple myeloma.
abstract: Bortezomib, a proteasome inhibitor with efficacy in multiple myeloma, is associated with thrombocytopenia, the cause and kinetics of which are different from those of standard cytotoxic agents. We assessed the frequency, kinetics, and mechanism of thrombocytopenia following treatment with bortezomib 1.3 mg/m2 in 228 patients with relapsed and/or refractory myeloma in 2 phase 2 trials. The mean platelet count decreased by approximately 60% during treatment but recovered rapidly between treatments in a cyclic fashion. Among responders, the pretreatment platelet count increased significantly during subsequent cycles of therapy. The mean percent reduction in platelets was independent of baseline platelet count, M-protein concentration, and marrow plasmacytosis. Plasma thrombopoietin levels inversely correlated with platelet count. Murine studies demonstrated a reduction in peripheral platelet count following a single bortezomib dose without negative effects on megakaryocytic cellularity, ploidy, or morphology. These data suggest that bortezomib-induced thrombocytopenia is due to a reversible effect on megakaryocytic function rather than a direct cytotoxic effect on megakaryocytes or their progenitors. The exact mechanism underlying bortezomib-induced thrombocytopenia remains unknown but it is unlikely to be related to marrow injury or decreased thrombopoietin production.
authors.affiliation: Winship Cancer Institute, Emory University, Atlanta, GA, USA. sloni01@emory.edu
authors.forename: Sagar
authors.initials: S
authors.lastname: Lonial
authors.forename: Edmund K
authors.initials: EK
authors.lastname: Waller
authors.forename: Paul G
authors.initials: PG
authors.lastname: Richardson
authors.forename: Sundar
authors.initials: S
authors.lastname: Jagannath
authors.forename: Robert Z
authors.initials: RZ
authors.lastname: Orlowski
authors.forename: Cynthia R
authors.initials: CR
authors.lastname: Giver
authors.forename: David L
authors.initials: DL
authors.lastname: Jaye
authors.forename: Dixil
authors.initials: D
authors.lastname: Francis
authors.forename: Sara
authors.initials: S
authors.lastname: Giusti
authors.forename: Claire
authors.initials: C
authors.lastname: Torre
authors.forename: Bart
authors.initials: B
authors.lastname: Barlogie
authors.forename: James R
authors.initials: JR
authors.lastname: Berenson
authors.forename: Seema
authors.initials: S
authors.lastname: Singhal
authors.forename: David P
authors.initials: DP
authors.lastname: Schenkein
authors.forename: Dixie-Lee W
authors.initials: DL
authors.lastname: Esseltine
authors.forename: Jessica
authors.initials: J
authors.lastname: Anderson
authors.forename: Hugh
authors.initials: H
authors.lastname: Xiao
authors.forename: Leonard T
authors.initials: LT
authors.lastname: Heffner
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Anderson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001897:Boronic Acids / Q000009:adverse effects*; D000069286:Bortezomib; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy*; D011719:Pyrazines / Q000009:adverse effects*; D012008:Recurrence; D012307:Risk Factors; D013921:Thrombocytopenia / Q000139:chemically induced*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib