Biological modifiers as cytoreductive therapy before stem cell transplant in previously untreated patients with multiple myeloma.
BACKGROUND
High dose chemotherapy with supporting autologous stem cell transplantation is now considered the treatment of choice in patients with multiple myeloma <65 years old. The best regimen appears to be VAD (vincristine, doxorubicin and dexamethasone), but acute and late toxicity can limit the use of this combination. The use of biological modifiers has not been considered in this situation. We developed a new cytoreductive regimen, in an attempt to retain clinical efficacy but reduce toxicity.


METHODS
Thirty-six patients, previously untreated with diagnosis of multiple myeloma were enrolled to received the DAI regimen (dexamethasone 30 mg/m(2), i.v., days 1-4, all-trans-retinoic acid 45 mg/m(2), p.o., days 5-14 and interferon alpha 2a, 4.5 MU s.c., days 5-14) administered every 28 days for six cycles before high-dose chemotherapy (melphalan 200 g/m(2)) and autologous stem cell transplantation.


RESULTS
Overall response was observed in 29 cases (80%), complete response in 19 and partial response in 10 patients. Five patients were >65 years old and were treated with dexamethasone/thalidomide. Twenty-four patients underwent transplants. At a median follow-up of 31.6 months, no relapse or disease progression was observed, thus actuarial curves at 3-years showed that event-free survival was 86% and overall survival was 94%. Toxicity was mild.


CONCLUSIONS
This regimen appears to be an excellent alternative as cytoreductive treatment before high-dose chemotherapy and autologous stem cell transplantation with excellent overall response and minimal toxicity. Controlled clinical trials are warranted to define the role of this new therapeutic approach.
Avilés
A
A
Oncology Research Unit and Department of Hematology, Oncology Hospital National Medical Center, México, D.F. Mexico. agaviles@avantel.net
Nambo
M J
MJ
Neri
N
N
Murillo
E
E
Castañeda
C
C
Cleto
S
S
Talavera
A
A
González
M
M
D000284:Administration, Oral; D000328:Adult; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D003907:Dexamethasone / Q000008:administration & dosage; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage; D008297:Male; D008558:Melphalan / Q000627:therapeutic use*; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy*; D036102:Peripheral Blood Stem Cell Transplantation; D011994:Recombinant Proteins; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D014212:Tretinoin / Q000008:administration & dosage
D018906:Antineoplastic Agents, Alkylating; D007155:Immunologic Factors; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D014212:Tretinoin; D003907:Dexamethasone; D008558:Melphalan