Clinical factors predictive of outcome with bortezomib in patients with relapsed, refractory multiple myeloma.
Bortezomib, a potent and reversible proteasome inhibitor, affects the myeloma cell and its microenvironment, resulting in down-regulation of growth and survival signaling pathways and durable responses in patients with relapsed and refractory myeloma. Potential associations between baseline parameters and outcomes with bortezomib were explored in 202 patients who received bortezomib 1.3 mg/m2 twice weekly for 2 weeks every 3 weeks for up to 8 cycles in a phase 2 trial. Using European Group for Blood and Marrow Transplantation criteria, the response rate (complete or partial response) to bortezomib alone was 27% and was not associated with sex, race, performance status, isotype, chromosome 13 deletion, number or type of previous therapies, or concentration of hemoglobin or beta2-microglobulin. By multivariate analysis, factors associated with lower response were being age 65 or older versus younger than 65 (19% vs 32%; P < .05) and plasma-cell infiltration in bone marrow greater than 50% versus 50% or less (20% vs 35%; P < .05). Factors that may be indicative of tumor burden (bone marrow plasma-cell infiltration greater than 50%, hypoalbuminemia, thrombocytopenia) were predictive of overall survival. Chromosome 13 deletion and elevated beta2-microglobulin, generally considered poor prognostic factors, were not predictive of poor outcome with bortezomib in this study.
Richardson
Paul Gerard Guy
PG
Department of Adult Oncology, Dana-Farber Cancer Institute, 44 Binney St, Dana 1B02, Boston, MA 02115, USA. paul_richardson@dfci.harvard.edu
Barlogie
Bart
B
Berenson
James
J
Singhal
Seema
S
Jagannath
Sundar
S
Irwin
David
D
Rajkumar
S Vincent
SV
Hideshima
Teru
T
Xiao
Hugh
H
Esseltine
Dixie
D
Schenkein
David
D
Anderson
Kenneth C
KC
D000368:Aged; D001897:Boronic Acids / Q000627:therapeutic use*; D000069286:Bortezomib; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000473:pathology*; D011719:Pyrazines / Q000627:therapeutic use*; D012008:Recurrence; D016896:Treatment Outcome
D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib