"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.
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.
Gasparetto
Cristina
C
Department of Cellular Therapy, Duke University Medical Center, Durham, NC 27710, USA. gaspa001@mc.duke.edu
Gockerman
Jon P
JP
Diehl
Louis F
LF
de Castro
Carlos M
CM
Moore
Joseph O
JO
Long
Gwynn D
GD
Horwitz
Mitchell E
ME
Keogh
George
G
Chute
John P
JP
Sullivan
Keith M
KM
Neuwirth
Rachel
R
Davis
Patricia H
PH
Sutton
Linda M
LM
Anderson
Russell D
RD
Chao
Nelson J
NJ
Rizzieri
David
D
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
D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D018931:Antineoplastic Agents, Hormonal; D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib; D008558:Melphalan; D011241:Prednisone