A Prospective Study of Bortezomib in Combination with Melphalan and Prednisone for Patients with Previously Untreated Multiple Myeloma.
Authors: Gasparetto Cristina , Keogh George P. , Gockerman Jon P. , Horwitz Mitchell , Moore Joseph O. , DeCastro Carlos , Diehl Louis , Davis Patty , Chao Nelson , Rizzieri David A. 
Published: April 2020

Abstract
The standard induction chemotherapy for patients with multiple myeloma (MM) is a dexamethasone based regimen including dexamethasone alone, VAD, thalidomide+dexamethasone and other combinations. Currently the overall response rate achieved with these regimens is ≤70% and the complete remission (CR) rate is &lt;10%. In order to improve the CR rate for both transplant and non-transplant candidates, other agents and regimens are being explored. Bortezomib (Velcade), a proteasome inhibitor currently approved in the USA and in Europe for the treatment of relapsed/refractory MM, has demonstrated an impressive activity in the treatment of myeloma. In relapsed/refractory MM, bortezomib has achieved response rate of 35%, with a median duration of response and overall survival of 14 and 18 months, respectively. Clinical experience in relapsed/refractory MM and in previously untreated patients has suggested that the combination of bortezomib with other anti-myeloma drugs could further improve the results achieved with bortezomib alone. We have recently initiated a prospective study to assess the combination of velcade, melphalan and prednisone (MPV) in patients with previously untreated MM. The primary objectives of this study are toxicity, feasibility and CR rate after 4 cycles. The regimen consisted of bortezomib 1.3 mg/m2 iv on day 1,4,8,11. melphalan 6 mg/m2 po, and prednisone 60 mg/m2 po given on days 1 through 7 of each cycle. As July 2005, 11 patients have been recruited. The median age is 64 (48–74) and all patients were Durie-Salmon stage IIIA. Nine of the 11 patients have completed ≥2 cycles of therapy, 6 patients have completed all 4 cycles of therapy and 3 patients were withdrawn from study (2 for pneumonia and 1 for grade 3 orthostatic hypotension). The most common adverse events were neuropathy (grade 1–3), neutropenia (grade 1–3), thrombocytopenia (grade1–3), fatigue, and bowel changes. For the 6 patients that have completed all 4 cycles of MPV, the responses were: 2/6 CR (negative SPEP/IFE); 1/6 very good partial remission (VGPR, 90% reduction of M-spike) and 3/6 partial remission (PR, 50% reduction of the serum M-spike). For the 3 patients who have completed only 2 cycles of therapy so far, 1/3 achieved a VGPR and 2/3 achieved a PR. Three patients have proceeded to stem cell collection and all engrafted following high dose therapy. Although experience is still limited and follow-up short, other than 3 patients withdrawn from study, all patients treated with MPV have responded to treatment and 2/6 patients achieved a CR. The best response was observed after cycle 2 in the majority of patients. Stem cell collection and engraftment was successful in all attempts so far. These data indicate that bortezomib combined with a short term alkylating regimen should be further explored as an induction regimen before transplantation in patients with myeloma.