Standard Chemotherapy Compared With High-Dose Chemoradiotherapy for Multiple Myeloma: Final Results of Phase III US Intergroup Trial S9321
Open accessAbstract
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/m 2 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.
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Randomized trials have consistently found similar overall survival with early ASCT versus delayed ASCT.
“However, randomized trials have consistently found similar OS with early ASCT (immediately following 4 cycles of induction therapy) versus delayed ASCT (at the time of relapse as salvage therapy).94,129–131”
From Multiple myeloma: 2024 update on diagnosis, risk-stratification, and management (2024) · cites this paper as [131]
The Clinical Outcome section reports identical 7-year overall survival estimates for patients randomized after four cycles of induction therapy to high-dose therapy or standard-dose therapy. It also reports that some patients in the standard-dose arm received a salvage autotransplant after relapse. The trial did not randomize patients to early versus delayed ASCT, so it supports similar survival between its treatment arms, not the stated timing comparison directly. (LLM, conf=0.86)
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Self-citationRetracted
- Authors
- Barlogie, B., Kyle, R. A., Anderson, K. C., Greipp, P. R., Lazarus, H. M., Hurd, D. D., McCoy, J., Moore, D. F., Dakhil, S. R., Lanier, K. S., Chapman, R. A., Cromer, J. N., Salmon, S. E., Durie, B., & Crowley, J. C.
- Affiliations
- Mayo Clinic (US)
- 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,...
- ORCID
- Venue
- Journal of Clinical Oncology
- Published
- 2006-02-20
- Volume
- 24
- Issue
- 6
- Pages
- 929-936
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- OpenAlex
- W2152333590
- Semantic Scholar
- bd39775d91e87b2a93f3181ada44755ab7f617fd
- Cited by
- 495
- References
- 41
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 7 · 2023: 7 · 2022: 13 · 2021: 12 · 2020: 22 · 2019: 14 · 2018: 16 · 2017: 27 · 2016: 25 · 2015: 22 · 2014: 23 · 2013: 40 · 2012: 33
- FWCI
- 33.36
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Oncology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Health and Human Services (CA38926, CA32102, CA31946)
- National Institutes of Health (5u10ca035117-10, 2u10ca038926-25, 5u10ca004920-35, 2u10ca058415-06)
- National Cancer Institute (U10CA016385, CA35192, U10CA004919, CA22-433, CA-58861, CA-58658, CA52654, CA 68183, CA-45377, U10CA035261, CA-76462, CA-35117, CA-35261, CA-46282, CA76132, CA37981, CA 20319, CA-32102, U10CA074647, CA 45450, CA03927, CA35119, CA-16385, CA58416, U10CA003927, CA 42777, U10CA045377, CA04919, U10CA068183, CA13650, U10CA014028, U10CA045560, CA27057, CA 74647, CA-58686, CA46368, CA46441, CA 04920, CA 63845, U10CA046368, CA-76429, CA67575, CA-12644, U10CA027057, U10CA035090, U10CA058686, CA 14028, U10CA020319, CA 46113, U10CA076429, U10CA014548, U10CA013612, U10CA032291, CA 58415, U10CA035119, U10CA058658, CA35431, U10CA032102, U10CA022433, U10CA046282, U10CA052654, CA14548, U10CA045450, U10CA031946, U10CA046113, U10CA012644, U10CA013650, U10CA042777, CA 13612, U10CA063845, CA 32291, U10CA063844, U10CA058416, U10CA035431, U10CA035192, CA 38926, CA63844, U10CA058861, CA-76447, U10CA037981, U10CA076447, CA45560, U10CA067575, CA-35090, CA-31946, U10CA046441)
- Topics
- Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
- Health Sciences › Medicine › Pathology and Forensic Medicine › Lymphoma Diagnosis and Treatment
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Keywords
- multiple myeloma, high-dose chemotherapy, chemoradiotherapy, autologous stem cell transplantation, melphalan, total body irradiation, standard-dose chemotherapy, progression-free survival, overall survival
- MeSH terms
- Adult, Aged, Antineoplastic Combined Chemotherapy Protocols, Carmustine, Clinical Protocols, Cyclophosphamide, Drug Administration Schedule, Female, Humans, Interferons, Male, Melphalan, Middle Aged, Multiple Myeloma, Prednisone, Prospective Studies, Transplantation, Autologous, Transplantation, Homologous, United States, Vincristine, Whole-Body Irradiation, Survival Analysis, Bone Marrow Transplantation, Salvage Therapy, Treatment Outcome, Chemotherapy, Adjuvant, Treatment Failure, Hematopoietic Stem Cell Transplantation, Disease-Free Survival, Radiotherapy, Adjuvant
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