Clinical factors predictive of outcome with bortezomib

From the Dana-Farber Cancer Institute, Boston, MA; University of Arkansas for Medical Sciences, Little Rock, AR; Cedars-Sinai Medical Center, Los Angeles, CA; Northwestern Memorial Hospital, Chicago, IL; St Vincent's Comprehensive Cancer Center, New York, NY; Alta Bates Cancer Center, Berkeley, CA; Mayo Clinic, Rochester, MN; and Millenium Pharmaceuticals, Inc., Cambridge, MA.

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 ₂-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 ₂-microglobulin, generally considered poor prognostic factors, were not predictive of poor outcome with bortezomib in this study.

Paul Gerard Guy Richardson, Bart Barlogie, James Berenson, Seema Singhal, Sundar Jagannath, David Irwin, S. Vincent Rajkumar, Teru Hideshima, Hugh Xiao, Dixie Esseltine, David Schenkein, Kenneth C. Anderson, for the SUMMIT Investigators