title: "Short course" bortezomib plus melphalan and prednisone as induction prior to transplant or as frontline therapy for nontransplant candidates in patients with previously untreated multiple myeloma.
abstract: The purpose of this study was to evaluate the efficacy and safety of short-course bortezomib, melphalan, prednisone (VMP) in previously untreated multiple myeloma as frontline therapy for transplant-ineligible patients and induction prior to autologous stem cell transplantation (ASCT). Patients received up to 6 28-day cycles of bortezomib 1.3 mg/m(2), days 1, 4, 8, and 11, plus melphalan 6 mg/m(2) and prednisone 60 mg/m(2), days 1-7. After 2-6 cycles, eligible and consenting patients could proceed to ASCT. Responses were assessed by International Uniform Response Criteria. The primary endpoint was complete response (CR) rate with VMP. Forty-five patients were enrolled. Among 44 evaluable patients, response rate was 95%, including 18% >or=CR (9% stringent CR), 27% very good partial responses (VGPR), and 50% partial responses (PR). Twenty patients proceeded to ASCT. Stem cell collection was successful in all; median yield was 5.6 x 10(6) CD34(+) cells/kg. Posttransplant response rates were 30% >or=CR (10% stringent CR), 65% VGPR, and 5% PR. After median follow-up of 14.0/14.6 months, median time to progression and progression-free survival were both 19.8/27.9 months in non-ASCT/ASCT patients. Seven patients have died; 1-year survival rates were 82%/95% in non-ASCT/ASCT patients. The most common grade 3/4 toxicities were thrombocytopenia (20%), neutropenia (28%), and infection (9%). Peripheral neuropathy grade 2-4 was the most common nonhematopoietic side effect occurring 17 patients (38%), although it was typically reversible, and only 5 patients (11%) discontinued therapy as a result of it. Short-course VMP is highly effective and generally well tolerated, both as initial treatment in non-ASCT patients and induction prior to ASCT. VMP did not negatively affect stem cell collection. Longer follow-up and prospective phase III trials are required to validate these initial observations.
authors.affiliation: Department of Cellular Therapy, Duke University Medical Center, Durham, NC 27710, USA. gaspa001@mc.duke.edu
authors.forename: Cristina
authors.initials: C
authors.lastname: Gasparetto
authors.forename: Jon P
authors.initials: JP
authors.lastname: Gockerman
authors.forename: Louis F
authors.initials: LF
authors.lastname: Diehl
authors.forename: Carlos M
authors.initials: CM
authors.lastname: de Castro
authors.forename: Joseph O
authors.initials: JO
authors.lastname: Moore
authors.forename: Gwynn D
authors.initials: GD
authors.lastname: Long
authors.forename: Mitchell E
authors.initials: ME
authors.lastname: Horwitz
authors.forename: George
authors.initials: G
authors.lastname: Keogh
authors.forename: John P
authors.initials: JP
authors.lastname: Chute
authors.forename: Keith M
authors.initials: KM
authors.lastname: Sullivan
authors.forename: Rachel
authors.initials: R
authors.lastname: Neuwirth
authors.forename: Patricia H
authors.initials: PH
authors.lastname: Davis
authors.forename: Linda M
authors.initials: LM
authors.lastname: Sutton
authors.forename: Russell D
authors.initials: RD
authors.lastname: Anderson
authors.forename: Nelson J
authors.initials: NJ
authors.lastname: Chao
authors.forename: David
authors.initials: D
authors.lastname: Rizzieri
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001897:Boronic Acids / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D000069286:Bortezomib; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects / Q000379:methods; D018450:Disease Progression; D004334:Drug Administration Schedule; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008558:Melphalan / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000628:therapy; D036102:Peripheral Blood Stem Cell Transplantation / Q000401:mortality; D011241:Prednisone / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D011719:Pyrazines / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D013223:Statistics as Topic; D014182:Transplantation, Autologous; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D018931:Antineoplastic Agents, Hormonal; D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib; D008558:Melphalan; D011241:Prednisone