Risk factors and kinetics of thrombocytopenia associated with bortezomib for relapsed, refractory multiple myeloma

Sagar Lonial*, Edmund K. Waller, Paul G. Richardson, Sundar Jagannath, Robert Z. Orlowski, Cynthia R. Giver, David L. Jaye, Dixil Francis, Sara Giusti, Claire Torre, Bart Barlogie, James R. Berenson, Seema Singhal, David P. Schenkein, Dixie Lee W Esseltine, Jessica Anderson, Hugh Xiao, Leonard T. Heffner, Kenneth C. Anderson

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

260 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)3777-3784
Number of pages8
JournalBlood
Volume106
Issue number12
DOIs
StatePublished - Dec 1 2005

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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