High-dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma.
BACKGROUND
High-dose therapy with supporting autologous stem-cell transplantation remains a controversial treatment for cancer. In multiple myeloma, first-line regimens incorporating high-dose therapy yield higher remission rates than do conventional-dose treatments, but evidence that this translates into improved survival is limited.


METHODS
In this multicenter study, the Medical Research Council Myeloma VII Trial, we randomly assigned 407 patients with previously untreated multiple myeloma who were younger than 65 years of age to receive either standard conventional-dose combination chemotherapy or high-dose therapy and an autologous stem-cell transplant.


RESULTS
Among the 401 patients who could be evaluated, the rates of complete response were higher in the intensive-therapy group than in the standard-therapy group (44 percent vs. 8 percent, P<0.001). The rates of partial response were similar (42 percent and 40 percent, respectively; P=0.72), and the rates of minimal response were lower in the intensive-therapy group than in the standard-therapy group (3 percent vs. 18 percent, P<0.001). Intention-to-treat analysis showed a higher rate of overall survival (P=0.04 by the log-rank test) and progression-free survival (P<0.001) in the intensive-therapy group than in the standard-therapy group. As compared with standard therapy, intensive treatment increased median survival by almost 1 year (54.1 months [95 percent confidence interval, 44.9 to 65.2] vs. 42.3 months [95 percent confidence interval, 33.1 to 51.6]). There was a trend toward a greater survival benefit in the group of patients with a poor prognosis, as defined by a high beta2-microglobulin level (more than 8 mg per liter).


CONCLUSIONS
High-dose therapy with autologous stem-cell rescue is an effective first-line treatment for patients with multiple myeloma who are younger than 65 years of age.
Child
J Anthony
JA
Academic Unit of Haematology and Oncology, Cancer Research United Kingdom Clinical Centre, University of Leeds, Leeds, United Kingdom. tony.child@leedsth.nhs.uk
Morgan
Gareth J
GJ
Davies
Faith E
FE
Owen
Roger G
RG
Bell
Susan E
SE
Hawkins
Kim
K
Brown
Julia
J
Drayson
Mark T
MT
Selby
Peter J
PJ
D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002330:Carmustine / Q000008:administration & dosage; D002423:Cause of Death; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008558:Melphalan / Q000008:administration & dosage*; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy / Q000401:mortality / Q000628:therapy*; D011379:Prognosis; D016019:Survival Analysis
D018906:Antineoplastic Agents, Alkylating; D004317:Doxorubicin; D003520:Cyclophosphamide; D008558:Melphalan; D002330:Carmustine