Originally published as JCO Early Release 10.1200/JCO.2005.04.5807 on January 23 2006

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Standard Chemotherapy Compared With High-Dose Chemoradiotherapy for Multiple Myeloma: Final Results of Phase III US Intergroup Trial S9321

Bart Barlogie, Robert A. Kyle, Kenneth C. Anderson, Philip R. Greipp, Hillard M. Lazarus, David D. Hurd, Jason McCoy, Dennis F. Moore, Jr, Shaker R. Dakhil, Keith S. Lanier, Robert A. Chapman, Jeana N. Cromer, Sydney E. Salmon, Brian Durie, John C. Crowley

From the University of Arkansas for Medical Science, Little Rock, AR; Mayo Clinic, Rochester, MN; Dana-Farber Cancer Institute, Boston, MA; University Hospitals of Cleveland, Cleveland, OH; Wake Forest University School of Medicine, Winston-Salem, NC; Southwest Oncology Group Statistical Center, Seattle, WA; Wichita Community Clinical Oncology Program, Wichita, KS; Columbia River Community Clinical Oncology Program, Portland, OR; Henry Ford Hospital, Detroit, MI; St Jude Children's Research Hospital, Memphis, TN; University of Arizona Cancer Center, Tucson, AZ; and Cedars Sinai Cancer Center, Los Angeles, CA
Deceased.

Address reprint requests to the Southwest Oncology Group (SWOG-9321), Operations Office, 14980 Omicron Dr, San Antonio, TX 78245-3217

PURPOSE: Results of a prospective randomized trial conducted by the Intergroupe Francais du Myélome (IFM 90) indicated that autologous hematopoietic cell–supported high-dose therapy (HDT) effected higher complete response rates and extended progression-free survial (PFS) and overall survival (OS) compared with standard-dose therapies (SDT) for patients with multiple myeloma (MM).

PATIENTS AND METHODS: In 1993, three North American cooperative groups launched a prospective randomized trial (S9321) comparing HDT (melphalan [MEL] 140 mg/m² plus total-body irradiation 12 Gy) with SDT using the vincristine, carmustine, MEL, cyclophosphamide, and prednisone regimen. Responders on both arms ( 75%) were randomly assigned to interferon (IFN) or no maintenance treatment.

RESULTS: With a median follow-up time of 76 months, no differences were observed in response rates between the two study arms (HDT, n = 261 patients; SDT, n = 255 patients). Similarly, PFS and OS durations did not differ between the HDT and SDT arms, with 7-year estimates of PFS of 17% and 16%, respectively, and OS of 37% and 42%, respectively. Of 242 patients achieving at least 75% tumor reduction, no difference was observed in PFS or OS among the 121 patients randomly assigned to IFN and the 121 patients randomly assigned to no maintenance therapy. Among 157 patients relapsing on SDT, 87 received a salvage autotransplantation; their median survival time of 30 months was only slightly better than the survival time of the remaining patients who were managed with further SDT (23 months; P = .13).

CONCLUSION: The HDT and SDT regimens used in S9321 yielded comparable response rates and PFS and OS durations. IFN maintenance therapy did not benefit patients who achieved 75% tumor reduction on either arm.

Supported in part by the following Public Health Service Cooperative Agreement Grants No. awarded by the National Cancer Institute, Department of Health and Human Services: CA38926, CA32102, CA13650, CA14548, CA31946, CA32291, CA03927, CA37981, CA35431, CA45377, CA58416, CA22433, CA58686, CA46113, CA04919, CA46441, CA58861, CA46282, CA35261, CA27057, CA76132, CA35192, CA76447, CA76462, CA45450, CA76429, CA63845, CA12644, CA20319, CA63844, CA45560, CA58415, CA14028, CA58658, CA42777, CA35119, CA35090, CA35117, CA13612, CA16385, CA67575, CA68183, CA46368, CA04920, CA74647, and CA52654; also supported in part by Amgen and Schering.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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