Phase I/II study of bortezomib‐melphalan‐prednisolone for previously untreated Japanese patients with multiple myeloma

Abstract

This phase I ⁄ II study was conducted to evaluate the safety and efficacy of bortezomib-melphalan-prednisolone in Japanese patients with previously untreated multiple myeloma who are ineligible for hematopoietic stem cell transplantation. One hundred and one patients were enrolled, and 99 patients received up to nine 6-week cycles of bortezomib (0.7 ⁄ 1.0 ⁄ 1.3 mg ⁄ m 2 ) on days 1,4,8,11, 22, 25, 29, and 32 in cycles 1-4 and on days 1, 8, 22, and 29 in cycles 5-9, with melphalan (9 mg ⁄ m 2 ) and prednisolone (60 mg ⁄ m 2 ) on days 1-4 of each cycle. The recommended dose was determined in the phase I portion, and the overall response rate and safety of bortezomib-melphalan-prednisolone at the recommended dose were assessed in the phase II portion. The recommended dose of bortezomib was determined to be 1.3 mg ⁄ m 2 . Grade 3 or higher non-hematological adverse events included diarrhea (12%) and peripheral neuropathy (10%); grade 4 hematological adverse events included lymphopenia (41%), neutropenia (30%), and thrombocytopenia (22%). Eleven patients had lung injury associated with bortezomib; two had grade 3 disease, and the other nine had grade 1 or 2 disease. Of the 86 patients treated with 1.3-mg ⁄ m 2 bortezomib in phases I and II, the median number of treatment cycles was 4.5, and the overall response rate was 70% (95% confidence interval: 59-79%). Bortezomib-melphalan-prednisolone with 1.3-mg ⁄ m 2 bortezomib was considered to be tolerable and effective in Japanese patients with previously untreated multiple myeloma. However, further investigation is needed to refine the administration schedule. (Cancer Sci 2013; 104: 912-919)

A prospective, open-label, multicenter, observational study to evaluate the efficacy and safety of bortezomib-melphalan-prednisone as initial treatment for autologous stem cell transplantation-ineligible patients with multiple myeloma

“…Table 6 summarizes the baseline characteristics and VMP treatment results from recently published studies [11, 14, 15]. The ORR in our study was similar to that from previous VMP studies.…”

Bortezomib, Melphalan, and Prednisone (VMP) Regimen for Multiple Myeloma

“…Several studies reviewed specified that the bortezomib was given IV. 4,6,8,13 4. In one study, the bortezomib was given SQ.…”

“…Neurologic: Neuralgia 36%, 4 (grade 3) 8%, 4 (grade 3 or 4) 7% to 9%, 5,11 (grade 4) 1% 4 ; peripheral neuropathy 55% to 59%, 2,3,11 (grade 1 or 2) 50%, 8 (grade 3 or 4) 7% to 23% 2,3,6,8,9 ; peripheral sensory neuropathy 44%, 4 (grade 3) 13%, 4 (grade 3 or 4) 13%, 5 …”

Bortezomib, Melphalan, and Prednisone (VMP) Regimen for Multiple Myeloma

“…Severe (grade 3 or 4) neutropenia was reported in 10% to 77% of patients. [2][3][4][5][6][7][8] Prophylactic use of CSFs is not recommended. 22,23 CSFs may be appropriate in some patients and should be considered if a patient experiences febrile neutropenia or grade 4 neutropenia in a prior cycle of VMP.…”

“…ALT/AST less than or equal to 2.5 times the ULN. 8 In clinical practice, a pretreatment ANC of 1,000 cells/mcL and platelets of 75,000 cells/ mcL are usually considered acceptable. Copyright of Hospital Pharmacy is the property of Thomas Land Publishers Incorporated and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission.…”