Background: Bortezomib (VELCADE™) is a reversible proteasome inhibitor that has been shown to be safe and efficacious in patients (pts) with relapsed and/or refractory multiple myeloma (MM) using a dose of 1.3 mg/m2 on days 1, 4, 8 & 11 of a 21-day cycle. Certain cytogenetic abnormalities are associated with poor prognosis in MM, including deletion 13, t(4;14) and the p53 deletion.(

Stewart et al, JCO 2005; 23(26):6339–44
). Bortezomib has demonstrated the ability to overcome the poor prognosis associated with deletion 13 (
Jagannath, JCO 2005; 23(16S) 6501
). The impact of bortezomib on a broader range of cytogenetic abnormalities, such as t(4;14) has yet to be determined.

Methods: In this multicentre, open-label, non-randomized, phase 3b study, pts with MM across 13 centres in Canada, who had received at least 2 previous lines of therapy and who were refractory to or had relapsed after their last therapy were enrolled. Pts received up to eight 3-week cycles of bortezomib on days 1, 4, 8 & 11. Dexamethasone 20 mg PO was administered on each day of and day after bortezomib administration if the pts either experienced progressive disease after receiving at least 2 treatment cycles of bortezomib or had no change in disease status from baseline after receiving at least 4 treatment cycles of bortezomib.

Results: 104 pts were enrolled; the mean age in this cohort was 60.7 years, and 65 (62.5%) were male. Approximately 30% of pts had a Karnofsky performance status of 70 or less at baseline. 71 pts (68.3%) had received prior thalidomide therapy, 32 (30.8%) had received a prior autotransplant and 4 (3.8%) had received prior bortezomib treatment. 74 (71.2%) received 3 or more lines of prior MM therapy. During the study, mean number of bortezomib cycles completed was 4.6 (range, 0–11 cycles), and the number of pts that completed 8 cycles of therapy was 36 (34.6%). 15.2% of pts received dexamethasone at cycle 3 and 19.2% at cycle 5. Cytogenetic analysis was performed on approximately half of the pts. Response data for cycle 5 is currently available for 69/99 (69.7%) of evaluable pts (see Table 1). Overall, 76.9% of the pts experienced Grade 3 & 4 adverse events. Safety profile observed is similar to past trial results with bortezomib.

Conclusion: In this large Canadian cohort of extensively pre-treated patients with mulitple myeloma, bortezomib demonstrated good response, consistent with previous studies. Analysis correlating cytogenetic profile and response rate is ongoing and will be available at the time of conference. In addition, a detailed safety analysis and impact of prior treatment on response will be analyzed and made available at the time of conference.

Table 1.

Response to Bortezomib

Category of Response*No. of Patients (%)
*Modified SWOG: CR 100% M-protein reduction; R 75–99%; PR 50–74%; MR 25–49%; SD<25%, PD increasing M-protein 
Any Response (CR + VGPR + PR + MR) 47 (68.1) 
---Complete Response (CR) + Very Good Partial Response (VGPR) ---22 (31.9) 
---Partial Response (PR) + Minimal Response (MR) ---25 (36.2) 
Stable Disease 10 (14.5) 
Progressive Disease 12 (17.4) 
Category of Response*No. of Patients (%)
*Modified SWOG: CR 100% M-protein reduction; R 75–99%; PR 50–74%; MR 25–49%; SD<25%, PD increasing M-protein 
Any Response (CR + VGPR + PR + MR) 47 (68.1) 
---Complete Response (CR) + Very Good Partial Response (VGPR) ---22 (31.9) 
---Partial Response (PR) + Minimal Response (MR) ---25 (36.2) 
Stable Disease 10 (14.5) 
Progressive Disease 12 (17.4) 

Disclosures: Deepa Sharma employed by Ortho Biotech (A Division of Janssen Ortho).; Drs. Joseph Mikhael, Donna Reece and Andrew Belch acted as consultants for Johnson and Johnson and Ortho Biotech (A Division of Janssen Ortho).; Dr. Donna Reece received research funding for bortezomib from Ortho Biotech (A Division of Janssen Ortho).; Drs. Joseph Mikhael, Donna Reece and Andrew Belch: Honoraria received for unrestricted educational lectures and advisory committee from Ortho Biotech (A Division of Janssen Ortho).; Drs. Joseph Mikhael and Andrew Belch: Advisory Committee for Ortho Biotech; Dr. Donna Reece: Speaker’s Bureau, Advisory Committee chair/speaker for Ortho Biotech (A Division of Janssen Ortho).; Dr. Donna Reece: Received one year funding for myeloma database entry person from Ortho Biotech (A Division of Janssen Ortho).

Author notes

*

Corresponding author

Sign in via your Institution