PHILADELPHIA—Two phase II clinical trials presented at the 44th Annual Meeting of the American Society of Hematology (ASH) have established the activity of the investigational proteasome inhibitor bortezomib(Drug information on bortezomib) (Velcade, also known as PS-341, Millennium Pharmaceuticals) in relapsed or refractory multiple myeloma.
Both trials used similar bortezomib regimens, with dexamethasone(Drug information on dexamethasone) added after several cycles to produce additional responses. The SUMMIT trial (abstract 385) reported an overall major response rate of 27% in 202 patients. The smaller CREST trial (abstract 3207), which evaluated two different doses, demonstrated similar response rates, which were dose related.
SUMMIT Results
Bortezomib is a first-in-class protea-some inhibitor that blocks NF-kB-mediated transcription of cytokines, adhesion molecules, angiogenesis factors, antiapoptotic factors, and other sub-stances that contribute to tumor growth (see drawing). Preclinical work suggests that bortezomib targets the myeloma cell and its environment, making it a promising agent for clinical trials, said Paul Richardson, MD, of the Dana-Farber Cancer Institute, who presented the SUMMIT results.
In this study, treatment consisted of bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11 of a 21-day cycle for up to eight cycles, with optional addition of dexa-methasone after the second cycle in the absence of benefit.
Patients were an average of 4½ years postdiagnosis and had received a median of six prior lines of therapy. Response was classified using the stringent Bladé criteria and required confirmation on two occasions 6 weeks apart.
Of 193 evaluable patients, complete remission (CR) was observed in 7 patients (4%). A further 12 patients (6%) achieved "near-CR" by meeting all Bladé criteria except absence of M protein on immunofixation, for an overall CR or near-CR rate of 10%. The overall response rate (complete, partial, and minor responses) was 35%, and 27% of patients had a major response, consisting of complete or partial remission. "In terms of the activity of bortezomib used alone, 70% of patients achieved stable disease or better," Dr. Richardson said.
