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

This Article Full Text Full Text (PDF) Publisher's Note Erratum (v24,p2687) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Barlogie, B. Articles by Crowley, J. C. Search for Related Content PubMed PubMed Citation Articles by Barlogie, B. Articles by Crowley, J. C. Social Bookmarking                            What's this?

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.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				J.-L. Harousseau, M. Attal, and H. Avet-Loiseau The role of complete response in multiple myeloma Blood, October 8, 2009; 114(15): 3139 - 3146. [Abstract] [Full Text] [PDF]

				A. J. Vangsted, T. W. Klausen, P. Gimsing, N. F. Andersen, N. Abildgaard, H. Gregersen, and U. Vogel A polymorphism in NFKB1 is associated with improved effect of interferon-{alpha} maintenance treatment of patients with multiple myeloma after high-dose treatment with stem cell support Haematologica, September 1, 2009; 94(9): 1274 - 1281. [Abstract] [Full Text] [PDF]

				S. Kumar, S. Giralt, E. A. Stadtmauer, J. L. Harousseau, A. Palumbo, W. Bensinger, R. L. Comenzo, S. Lentzsch, N. Munshi, R. Niesvizky, et al. Mobilization in myeloma revisited: IMWG consensus perspectives on stem cell collection following initial therapy with thalidomide-, lenalidomide-, or bortezomib-containing regimens Blood, August 27, 2009; 114(9): 1729 - 1735. [Abstract] [Full Text] [PDF]

				M. A. Hussein, V. Bolejack, J. A. Zonder, B. G.M. Durie, A. J. Jakubowiak, J. J. Crowley, and B. Barlogie Phase II Study of Thalidomide Plus Dexamethasone Induction Followed by Tandem Melphalan-Based Autotransplantation and Thalidomide-Plus-Prednisone Maintenance for Untreated Multiple Myeloma: A Southwest Oncology Group Trial (S0204) J. Clin. Oncol., July 20, 2009; 27(21): 3510 - 3517. [Abstract] [Full Text] [PDF]

				S. Wang, G. Tricot, L. Shi, W. Xiong, Z. Zeng, H. Xu, M. Zangari, B. Barlogie, J. D. Shaughnessy Jr, and F. Zhan RAR{alpha}2 expression is associated with disease progression and plays a crucial role in efficacy of ATRA treatment in myeloma Blood, July 16, 2009; 114(3): 600 - 607. [Abstract] [Full Text] [PDF]

				J.-L. Harousseau and P. Moreau Autologous Hematopoietic Stem-Cell Transplantation for Multiple Myeloma N. Engl. J. Med., June 18, 2009; 360(25): 2645 - 2654. [Full Text] [PDF]

				M. Rotta, B. E. Storer, F. Sahebi, J. A. Shizuru, B. Bruno, T. Lange, E. D. Agura, P. A. McSweeney, M. A. Pulsipher, P. Hari, et al. Long-term outcome of patients with multiple myeloma after autologous hematopoietic cell transplantation and nonmyeloablative allografting Blood, April 2, 2009; 113(14): 3383 - 3391. [Abstract] [Full Text] [PDF]

				B. Bruno, M. Rotta, F. Patriarca, D. Mattei, B. Allione, F. Carnevale-Schianca, R. Sorasio, A. Rambaldi, M. Casini, M. Parma, et al. Nonmyeloablative allografting for newly diagnosed multiple myeloma: the experience of the Gruppo Italiano Trapianti di Midollo Blood, April 2, 2009; 113(14): 3375 - 3382. [Abstract] [Full Text] [PDF]

				A. A Saad, M. Sharma, and G. M Higa Treatment of Multiple Myeloma in the Targeted Therapy Era Ann. Pharmacother., February 1, 2009; 43(2): 329 - 338. [Abstract] [Full Text] [PDF]

				J. Mehta One or two autografts for myeloma? Blood, April 1, 2008; 111(7): 3899 - 3900. [Full Text] [PDF]

				R. A. Kyle and S. V. Rajkumar Multiple myeloma Blood, March 15, 2008; 111(6): 2962 - 2972. [Abstract] [Full Text] [PDF]

				S. K. Kumar, S. V. Rajkumar, A. Dispenzieri, M. Q. Lacy, S. R. Hayman, F. K. Buadi, S. R. Zeldenrust, D. Dingli, S. J. Russell, J. A. Lust, et al. Improved survival in multiple myeloma and the impact of novel therapies Blood, March 1, 2008; 111(5): 2516 - 2520. [Abstract] [Full Text] [PDF]

				W. Bensinger Stem-Cell Transplantation for Multiple Myeloma in the Era of Novel Drugs J. Clin. Oncol., January 20, 2008; 26(3): 480 - 492. [Abstract] [Full Text] [PDF]

				J.-P. Fermand Initial Therapy for Multiple Myeloma: Role of Stem Cell Transplantation ASCO Educational Book, January 1, 2008; 2008(1): 375 - 379. [Abstract] [Full Text] [PDF]

				D. Dingli, J. M. Pacheco, G. S. Nowakowski, S. K. Kumar, A. Dispenzieri, S. R. Hayman, M. Q. Lacy, D. A. Gastineau, and M. A. Gertz Relationship Between Depth of Response and Outcome in Multiple Myeloma J. Clin. Oncol., November 1, 2007; 25(31): 4933 - 4937. [Abstract] [Full Text] [PDF]

				M. A. Dimopoulos, V. L. Souliotis, A. Anagnostopoulos, C. Bamia, A. Pouli, I. Baltadakis, E. Terpos, S. A. Kyrtopoulos, and P. P. Sfikakis Melphalan-induced DNA damage in vitro as a predictor for clinical outcome in multiple myeloma Haematologica, November 1, 2007; 92(11): 1505 - 1512. [Abstract] [Full Text] [PDF]

				J. A. Katzel, P. Hari, and D. H. Vesole Multiple Myeloma: Charging Toward a Bright Future CA Cancer J Clin, September 1, 2007; 57(5): 301 - 318. [Abstract] [Full Text] [PDF]

				Y.-T. Tai, M. Fulciniti, T. Hideshima, W. Song, M. Leiba, X.-F. Li, M. Rumizen, P. Burger, A. Morrison, K. Podar, et al. Targeting MEK induces myeloma-cell cytotoxicity and inhibits osteoclastogenesis Blood, September 1, 2007; 110(5): 1656 - 1663. [Abstract] [Full Text] [PDF]

				R. Manochakian, K. C. Miller, and A. A. Chanan-Khan Clinical Impact of Bortezomib in Frontline Regimens for Patients with Multiple Myeloma Oncologist, August 1, 2007; 12(8): 978 - 990. [Abstract] [Full Text] [PDF]

				P. Sonneveld, B. van der Holt, C. M. Segeren, E. Vellenga, A. J. Croockewit, G. E.G. Verhoef, J. J. Cornelissen, M. R. Schaafsma, M. H.J. van Oers, P. W. Wijermans, et al. Intermediate-dose melphalan compared with myeloablative treatment in multiple myeloma: long-term follow-up of the Dutch Cooperative Group HOVON 24 trial Haematologica, July 1, 2007; 92(7): 928 - 935. [Abstract] [Full Text] [PDF]

				P. G. Richardson, C. Mitsiades, R. Schlossman, N. Munshi, and K. Anderson New Drugs for Myeloma Oncologist, June 1, 2007; 12(6): 664 - 689. [Abstract] [Full Text] [PDF]

				S. Y. Kristinsson, O. Landgren, P. W. Dickman, A. R. Derolf, and M. Bjorkholm Patterns of Survival in Multiple Myeloma: A Population-Based Study of Patients Diagnosed in Sweden From 1973 to 2003 J. Clin. Oncol., May 20, 2007; 25(15): 1993 - 1999. [Abstract] [Full Text] [PDF]

				B. Bruno, M. Rotta, F. Patriarca, N. Mordini, B. Allione, F. Carnevale-Schianca, L. Giaccone, R. Sorasio, P. Omede, I. Baldi, et al. A Comparison of Allografting with Autografting for Newly Diagnosed Myeloma N. Engl. J. Med., March 15, 2007; 356(11): 1110 - 1120. [Abstract] [Full Text] [PDF]

				A. Dispenzieri, S. V. Rajkumar, M. A. Gertz, M. Q. Lacy, R. A. Kyle, P. R. Greipp, T. E. Witzig, J. A. Lust, S. J. Russell, S. R. Hayman, et al. Treatment of Newly Diagnosed Multiple Myeloma Based on Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART): Consensus Statement Mayo Clin. Proc., March 1, 2007; 82(3): 323 - 341. [Abstract] [Full Text] [PDF]

				M. Attal, P. Moreau, H. Avet-Loiseau, and J.-L. Harousseau Stem Cell Transplantation in Multiple Myeloma Hematology, January 1, 2007; 2007(1): 311 - 316. [Abstract] [Full Text] [PDF]

				S. Singhal and J. Mehta Multiple Myeloma Clin. J. Am. Soc. Nephrol., November 1, 2006; 1(6): 1322 - 1330. [Abstract] [Full Text] [PDF]

				M.-V. Mateos, J.-M. Hernandez, M.-T. Hernandez, N.-C. Gutierrez, L. Palomera, M. Fuertes, J. Diaz-Mediavilla, J.-J. Lahuerta, J. de la Rubia, M.-J. Terol, et al. Bortezomib plus melphalan and prednisone in elderly untreated patients with multiple myeloma: results of a multicenter phase 1/2 study Blood, October 1, 2006; 108(7): 2165 - 2172. [Abstract] [Full Text] [PDF]

				I. Hanamura, J. P. Stewart, Y. Huang, F. Zhan, M. Santra, J. R. Sawyer, K. Hollmig, M. Zangarri, M. Pineda-Roman, F. van Rhee, et al. Frequent gain of chromosome band 1q21 in plasma-cell dyscrasias detected by fluorescence in situ hybridization: incidence increases from MGUS to relapsed myeloma and is related to prognosis and disease progression following tandem stem-cell transplantation Blood, September 1, 2006; 108(5): 1724 - 1732. [Abstract] [Full Text] [PDF]