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.
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.
Authors: D H Vesole; J J Crowley; R Catchatourian; P J Stiff; D B Johnson; J Cromer; S E Salmon; B Barlogie Journal: J Clin Oncol Date: 1999-07 Impact factor: 44.544
Authors: J F San-Miguel; P G Richardson; P Sonneveld; M W Schuster; D Irwin; E A Stadtmauer; T Facon; J-L Harousseau; D Ben-Yehuda; S Lonial; H Goldschmidt; D Reece; J Bladé; M Boccadoro; J D Cavenagh; R Neuwirth; A L Boral; D-L Esseltine; K C Anderson Journal: Leukemia Date: 2008-01-17 Impact factor: 11.528
Authors: Paul G Richardson; Bart Barlogie; James Berenson; Seema Singhal; Sundar Jagannath; David Irwin; S Vincent Rajkumar; Gordan Srkalovic; Melissa Alsina; Raymond Alexanian; David Siegel; Robert Z Orlowski; David Kuter; Steven A Limentani; Stephanie Lee; Teru Hideshima; Dixie-Lee Esseltine; Michael Kauffman; Julian Adams; David P Schenkein; Kenneth C Anderson Journal: N Engl J Med Date: 2003-06-26 Impact factor: 91.245
Authors: J Bladé; D Samson; D Reece; J Apperley; B Björkstrand; G Gahrton; M Gertz; S Giralt; S Jagannath; D Vesole Journal: Br J Haematol Date: 1998-09 Impact factor: 6.998
Authors: G L Uy; S D Goyal; N M Fisher; A Y Oza; M H Tomasson; K Stockerl-Goldstein; J F DiPersio; R Vij Journal: Bone Marrow Transplant Date: 2008-11-24 Impact factor: 5.483