BACKGROUND: In elderly patients with newly diagnosed multiple myeloma (MM), the addition of bortezomib to standard, combined oral melphalan and prednisone (MP) significantly increases the response rate and event-free survival compared with MP alone. METHODS: In this phase 1/2 trial, the authors assessed the dosing, efficacy, and safety of a lower dose-intensity MP schedule plus weekly bortezomib as salvage treatment for elderly patients with MM. To assess the maximum tolerated dose, 19 patients who had relapsed/refractory MM after 1 or 2 lines of treatment entered the first phase of the study. They received melphalan at a dose of 24 mg for 28 days; bortezomib 1.3 mg/m(2) on days 1, 8, 15, and 22; and prednisone at a dose of 50 mg every other day of a 28-day cycle for a total of 9 cycles. At the end of the first phase, based on the good efficacy and acceptable toxicity of this combination, an additional 23 patients were enrolled. RESULTS: After a median follow-up of 21 months, of 42 patients who relapsed, 24 (57%) obtained at least a partial response, 4 had stable disease, and 11 had progressive disease. The median time to progression was 18 months, and the median overall survival was 30 months. Grade 3 and 4 toxicity was observed in 16 of 42 patients (38%) and was more frequent during the early cycles. CONCLUSIONS: A weekly infusion of bortezomib associated with lower dose-intensity MP induced a high proportion of responses and was well tolerated in elderly patients with relapsed/refractory MM.
BACKGROUND: In elderly patients with newly diagnosed multiple myeloma (MM), the addition of bortezomib to standard, combined oral melphalan and prednisone (MP) significantly increases the response rate and event-free survival compared with MP alone. METHODS: In this phase 1/2 trial, the authors assessed the dosing, efficacy, and safety of a lower dose-intensity MP schedule plus weekly bortezomib as salvage treatment for elderly patients with MM. To assess the maximum tolerated dose, 19 patients who had relapsed/refractory MM after 1 or 2 lines of treatment entered the first phase of the study. They received melphalan at a dose of 24 mg for 28 days; bortezomib 1.3 mg/m(2) on days 1, 8, 15, and 22; and prednisone at a dose of 50 mg every other day of a 28-day cycle for a total of 9 cycles. At the end of the first phase, based on the good efficacy and acceptable toxicity of this combination, an additional 23 patients were enrolled. RESULTS: After a median follow-up of 21 months, of 42 patients who relapsed, 24 (57%) obtained at least a partial response, 4 had stable disease, and 11 had progressive disease. The median time to progression was 18 months, and the median overall survival was 30 months. Grade 3 and 4 toxicity was observed in 16 of 42 patients (38%) and was more frequent during the early cycles. CONCLUSIONS: A weekly infusion of bortezomib associated with lower dose-intensity MP induced a high proportion of responses and was well tolerated in elderly patients with relapsed/refractory MM.
Authors: Meletios A Dimopoulos; A Keith Stewart; Tamás Masszi; Ivan Špička; Albert Oriol; Roman Hájek; Laura Rosiñol; David Siegel; Georgi G Mihaylov; Vesselina Goranova-Marinova; Péter Rajnics; Aleksandr Suvorov; Ruben Niesvizky; Andrzej Jakubowiak; Jesus San-Miguel; Heinz Ludwig; Antonio Palumbo; Mihaela Obreja; Sanjay Aggarwal; Philippe Moreau Journal: Br J Haematol Date: 2017-02-17 Impact factor: 6.998