A phase II open-label trial of bortezomib in patients with multiple myeloma who have undergone an autologous peripheral blood stem cell transplant and failed to achieve a complete response
Background A majority of multiple myeloma (MM) patients fail to achieve complete response (CR) to peripheral blood stem cell transplantation (PBSCT); effective options following autologous transplantation are needed. Bortezomib (B) is active against MM. This study was conducted to determine the feasibility, safety, tolerability, and efficacy of B following high-dose melphalan therapy and PBSCT. Methods Fifty patients enrolled (48 evaluable) and 49 were treated (safety population). Treatment: 4 cycles B 1.3 mg/m2 Days 1, 4, 8, and 11/21-days; 4 additional cycles were permitted for stable or responding patients. Results Median age was 55 years (range, 38–73), 68% male, 64% ECOG PS = 0, 44% Durie-Salmon Stage IIIA prior to induction, 42% had symptomatic IgG MM; 74% had prior single transplant (26% tandem). Responses post-transplant: 70% PRs, 18% MRs. A median of 4 cycles (range, 2–8) of B were administered. Responses: CR 8%, uCR 2%, PR 23%, uPR 19%, MR 10%, and no change 35%; median time-to-treatment failure (TTF) was 6.2 months (range, 1.0–19.4). Three deaths occurred (n = 1 sepsis, n = 2 disease progression). Grade 3–4 treatment-related toxicities included: thrombocytopenia, neuropathy (14%, each); asthenia, neutropenia (10%, each); and nausea (4%). Twelve patients (24%) discontinued treatment due to toxicity and 30 patients (60%) completed the study; 20 patients started new treatment (median 5.8 months [range, 1.5–20.3]). Conclusions The study closed early due to widespread availability of B, and the lack of B-naïve patients. Bortezomib monotherapy after melphalan and autologous PBSCT was feasible, safe and well-tolerated (toxicities were manageable), but failed to produce the hypothesized response rates.
KeywordsAutologous Bortezomib Community-based Multicenter Peripheral blood stem cell transplant Proteasome inhibition
We thank the patients who shared their experiences with US Oncology physicians (see Appendix), the site coordinators in the field (especially Kim K. Seeley, BSN, OCN and Nichole M. Stephens, BSN), and program manager Julie Boston, RN; project managers Sharon Ambro, RN and Mary Ann Rauch, BS; and, clinical data specialist Tracy Locke, BA, RHIA, who all ensured the accuracy of the data.
Conflict of Interest Disclosures
The following disclosures apply: Dr. Rifkin is on the Speakers’ Bureau and Advisory Board for Millennium. All other authors have nothing to disclose.
Bortezomib (Velcade®) is produced by Millennium Pharmaceuticals, Inc., Cambridge, MA.
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