1. 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.
- Author
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Rifkin RM, Greenspan A, Schwerkoske JF, Mandanas RA, Stephenson JJ, Kannarkat GT, Zhan F, Boehm KA, Asmar L, and Beveridge R
- Subjects
- Aged, Antineoplastic Agents adverse effects, Boronic Acids adverse effects, Bortezomib, Chemotherapy, Adjuvant, Chi-Square Distribution, Disease Progression, Disease-Free Survival, Feasibility Studies, Female, Humans, Kaplan-Meier Estimate, Male, Melphalan therapeutic use, Middle Aged, Multiple Myeloma mortality, Myeloablative Agonists therapeutic use, Pyrazines adverse effects, Time Factors, Transplantation, Autologous, Treatment Failure, United States, Antineoplastic Agents therapeutic use, Boronic Acids therapeutic use, Multiple Myeloma drug therapy, Multiple Myeloma surgery, Peripheral Blood Stem Cell Transplantation, Pyrazines therapeutic use
- Abstract
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/m(2) 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.
- Published
- 2012
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