Characterisation of haematological profiles and low risk of thromboembolic events with bortezomib in patients with relapsed multiple myeloma.
Haematological toxicities and thromboembolic (TE) events are common complications of myeloma therapy. TE risk may be elevated with combination regimens, notably thalidomide/lenalidomide plus high-dose dexamethasone; concomitant erythropoietin appears to further increase the risk with lenalidomide-dexamethasone. We characterised thrombocytopenia and neutropenia in the phase 3 APEX (Assessment of Proteasome Inhibition for Extending Remissions) study of bortezomib versus high-dose dexamethasone in relapsed myeloma, and calculated the incidences of deep-vein thrombosis (DVT)/pulmonary embolism (PE) with: bortezomib or dexamethasone +/- erythropoietin in APEX; bortezomib +/- dexamethasone +/- erythropoietin in two phase 2 studies of relapsed/refractory myeloma. Bortezomib-associated thrombocytopenia and neutropenia were transient, predictable and manageable; mean platelet and neutrophil counts followed a cyclical pattern, and improved over the treatment course. Grade 3/4 thrombocytopenia incidence was higher with bortezomib versus dexamethasone (26%/4% vs. 5%/1%), but significant bleeding events were comparable (4% vs. 5%). DVT/PE incidence was low (< or =3.1%) in all analyses; addition of dexamethasone/erythropoietin did not affect TE risk. In APEX, TE risk appeared lower with bortezomib versus dexamethasone. Bortezomib caused transient and cyclical thrombocytopenia and was not associated with elevated TE risk, alone or with dexamethasone +/- erythropoietin. Preliminary data suggest bortezomib may reduce the thrombogenic potential of combination regimens via inhibition of platelet function or other mechanism-specific effects on coagulation.
Lonial
Sagar
S
Emory University, Atlanta, GA 30322, USA. sloni01@emory.edu
Richardson
Paul G
PG
San Miguel
Jesús
J
Sonneveld
Pieter
P
Schuster
Michael W
MW
Bladé
Joan
J
Cavenagh
Jamie
J
Rajkumar
S Vincent
SV
Jakubowiak
Andrzej J
AJ
Esseltine
Dixie-Lee
DL
Anderson
Kenneth C
KC
Harousseau
Jean-Luc
JL
D001897:Boronic Acids / Q000627:therapeutic use*; D000069286:Bortezomib; D002986:Clinical Trials as Topic; D003907:Dexamethasone / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D004921:Erythropoietin / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood / Q000188:drug therapy*; D011480:Protease Inhibitors / Q000627:therapeutic use*; D011655:Pulmonary Embolism / Q000150:complications; D011719:Pyrazines / Q000627:therapeutic use*; D011994:Recombinant Proteins; D012008:Recurrence; D012306:Risk; D016896:Treatment Outcome; D020246:Venous Thrombosis / Q000150:complications
D001897:Boronic Acids; D007166:Immunosuppressive Agents; D011480:Protease Inhibitors; D011719:Pyrazines; D011994:Recombinant Proteins; D004921:Erythropoietin; D000069286:Bortezomib; D003907:Dexamethasone