Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Long-term survival of stage I multiple myeloma given chemotherapy just after diagnosis or at progression of the disease: a multicentre randomized study

This article has been updated

Abstract

We conducted a randomized trial to evaluate whether melphalan-prednisone (MPH-P) treatment administered just after diagnosis improves survival of stage I multiple myeloma (MM). Between January 1987 and March 1993, 145 consecutive previously untreated patients with stage I MM were randomized between treatment with MPH-P (administered for 4 days every 6 weeks) just after diagnosis and treatment only at disease progression. Survival was not influenced by MPH-P treatment either administered just after diagnosis or at disease progression (64 vs 71 months respectively). Comparing the first with the second group the odds ratio of death is 1.17 (95% confidence interval 0.57–2.42;P = 0.64). Disease progression occurred within a year in about 50% of patients who were initially untreated. Response rate was similar in both groups, but duration of response was shorter in patients who were treated at disease progression (48 vs 79 months, P = 0.044). Patients actually treated at disease progression (34/70) survived shorter than those who had neither disease progression nor treatment (56 vs > 92 months;P = 0.005). Starting MPH-P just after diagnosis does not improve survival and response rate in stage I MM, with respect to deferring therapy until disease progression. However, patients with stage I MM randomized to have treatment delayed and who actually progressed and were treated had shorter survival than those with stable disease and no treatment. Biologic or other disease features could identify these subgroups of patients. © 2000 Cancer Research Campaign

Change history

  • 16 November 2011

    This paper was modified 12 months after initial publication to switch to Creative Commons licence terms, as noted at publication

References

  • Attal M, Harousseau JL, Stoppa AM, Sotto JJ, Fuzibet JG, Rossi JF, Casassus P, Maisonneuve H, Facon T, Ifrah N, Payen C and Bataille R and for the Intergroup Francaise du Myelome (1996) A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. N Engl J Med 335: 91–97

    CAS  Article  Google Scholar 

  • Bataille R and Harousseau JL (1997) Multiple myeloma. N Engl J Med 336: 1657–1664

    CAS  Article  Google Scholar 

  • Bergsagel DE (1988) Chemotherapy of myeloma: drug combinations versus single agents, and overview, and comments on acute leukemia in myeloma. Hematol Oncol 6: 159–166

    CAS  Article  Google Scholar 

  • Besinger WI, Rowley SD, Demirer T, Lilleby K, Schiffman K, Clift RA, Appelbaum FR, Fefer A, Barnett T, Storb R, Chauncey T, Maziarz RT, Klarnet J, McSweeney P, Holmberg L, Maloney DG, Weaver CH and Buckner CD (1996) High dose therapy followed by autologous hematopoietic stem-cell infusion for patients with multiple myeloma. J Clin Oncol 14: 1447–1456

    Article  Google Scholar 

  • Björkstrand B, Goldstone AH, Ljungman P, Brandt L, Brunet S, Carlson K, Prentice G, Cavo M, Samson D, De Laurenzi A, Verdonck LF, Proctor S, Ferrant A, Sierra J, Auzanneau G, Troussard X, Gravett P, Remes K and Gahrton G and for the European Group for Bone Marrow Transplantation (1994) Prognostic factors in autologous stem cell transplantation for multiple myeloma: an EBMT registry study. Leuk Lymphoma 15: 265–272

    Article  Google Scholar 

  • Cohen HJ, Silberman HR, Larsen WE, Johnson L, Bartolucci Durant JR (1979) Combination chemotherapy with intermittent 1-3(bis-2-chloroethyl)-1-nitrosurea (BCNU), cyclophosphamide and prednisone for multiple myeloma. Blood 54: 824–836

    CAS  PubMed  Google Scholar 

  • Cunningham D, Paz-Arez L, Milan S, Powles R, Nicolson M, Hickish T, Selby P, Treleavan J, Viner C, Malpas J, Slevin M, Findlay M, Raymond J and Gore ME (1994) High dose melphalan and autologous bone marrow transplantation as consolidation in previously untreated myeloma. J Clin Oncol 12: 759–763

    CAS  Article  Google Scholar 

  • Danova M, Riccardi A, Ucci G, Luoni R, Giordano M and Mazzini G (1990) Ras oncogene expression and DNA content in plasma cell dyscrasia: a flow cytofluorimetric study. Br J Cancer 62: 781–785

    CAS  Article  PubMed Central  Google Scholar 

  • Dighiero G, Maloum K, Desablens B, Cazin B, Navarro M, Leblay R, Leporrier M, Jaubert J, Lepeu G, Dreyfus B, Binet JL and Travade P and for the French Cooperative Group on Chronic Lymphocytic Leukemia (1998) Chlorambucil in indolent chronic lymphocytic leukemia. N Engl J Med 338: 1506–1514

    CAS  Article  Google Scholar 

  • Dimopoulos MA, Moulopoulos A, Smith T, Delasalle KB and Alexanian R (1993) Risk of disease progression in asymptomatic multiple myeloma. Am J Med 94: 57–61

    CAS  Article  Google Scholar 

  • Drewinko B, Alexanian R, Boyer H, Barlogie B and Rubinow SI (1981) The growth rate of human myeloma cells. Blood 57: 333–338

    CAS  PubMed  Google Scholar 

  • Durie BGM and Salmon SE (1975) A clinical staging system for multiple myeloma. Cancer 36: 842–854

    CAS  Article  Google Scholar 

  • Facon T, Menard JF, Michaux JL, Euller-Ziegler L, Bernard JF, Grosbois B, Daragon A, Azais I, Courouble Y, Kaplan G, Laport JP, De Gramont A, Duclos B, Leonard A, Mineur P, Delannoy A, Jouet JP, Bauters F and Monconduit M (1995) Prognostic factors in low tumour mass asymptomatic multiple myeloma: a report on 91 patients. Am J Hematol 48: 71–75

    CAS  Article  Google Scholar 

  • Fermand JP, Chevret S, Ravaud P, Divine M, Leblonde V, Dreyfus F, Mariette X and Brouet JC (1993) High-dose chemoradiotherapy and autologous blood stem cell transplantation in multiple myeloma: results of a phase II trial involving 63 patients. Blood 82: 2005–2009

    CAS  PubMed  Google Scholar 

  • Harousseau JL, Attal M, Divine M, Marit G, Leblond V, Stoppa AM, Bourhis JH, Caillot D, Boasson M, Abgrall JF, Facon T, Linassier C, Cahn JY, Lamy T, Troussrd X, Gratecos N, Pignon B, Auzanneau G and Bataille R (1995) Autologous stem cells transplantation after first remission induction treatment in multiple myeloma: a report of the French Registry on autologous transplantation in multiple myeloma. Blood 85: 3077–3085

    CAS  PubMed  Google Scholar 

  • Hjorth M, Hellquist L, Holmberg E, Magnusson B, Rödier S and Westin J (1993) Initial versus deferred melphalan-prednisone therapy for asymptomatic multiple myeloma stage I: a randomized study. Eur J Haematol 50: 95–102

    CAS  Article  Google Scholar 

  • Jagannath S, Barlogie B, Vesole D, Alexanian R, Tricot G and Crowley J (1993) Two-hundred sixty autotransplants (TX) for multiple myeloma (MM): prognostic factor analysis. Blood 82: 198a (abstract 779)

    Google Scholar 

  • Kyle RA (1993) “Benign” monoclonal gammopathy: after 20 to 35 years of follow-up. Mayo Clinic Proc 68: 26–36

    CAS  Article  Google Scholar 

  • Mariette X, Zagdanski AM, Guermazi A, Bergot C, Arnould A, Frija J, Brouet JC and Fermand JP (1999) Prognostic value of vertebral lesions detected by magnetic resonance imaging in patients with stage I multiple myeloma. Br J Haematol 104: 723–729

    CAS  Article  Google Scholar 

  • Marit G, Faberes C, Pico JL, Boiron JM, Bourhis JH, Brault P, Bernard P, Foures C, Cony-Makhoul P, Puntous M, Vezon G, Broustet A, Girault D and Reiffers J (1996) Autologous peripheral-blood progenitor-cell support following high-dose chemotherapy or chemoradiotherapy in patients with high-risk multiple myeloma. J Clin Oncol 14: 1306–1313

    CAS  Article  Google Scholar 

  • Montecucco CM, Riccardi A, Merlini GP, Mazzini G, Giordano P, Danova M and Ascari E (1984) Plasma cell DNA content in multiple myeloma and related paraproteinemic disorders. Relationship with clinical and cytokinetic features. Eur J Cancer 20: 81–89

    CAS  Article  Google Scholar 

  • Riccardi A, Montecucco CM, Danova M, Ucci G, Merlini GP and Ascari E (1985) Rate of M-component changes and plasma cell labeling index in 25 patients with multiple myeloma treated with Peptichemio. Cancer Treat Rep 69: 971–975

    CAS  PubMed  Google Scholar 

  • Riccardi A, Ucci G, Luoni R, Castello A, Coci A, Magrini U and Ascari E and for the Cooperative Group of Study and Treatment of Multiple Myeloma (1990) Bone marrow biopsy in monoclonal gammopathies: correlations between pathologic findings and clinical data. J Clin Pathol 43: 469–475

    CAS  Article  PubMed Central  Google Scholar 

  • Riccardi A, Gobbi P, Ucci G, Bertoloni D, Luoni R, Rutigliano L and Ascari E (1991) Changing clinical presentation of multiple myeloma. Eur J Cancer 27: 1401–1405

    CAS  Article  Google Scholar 

  • Riccardi A, Ucci G, Luoni R, Brugnatelli S, Mora O, Spanedda R, De Paoli A, Barbarano L, Di Stasi M, Alberio F, Delfini C, Nicoletti G, Morandi S, Rinaldi E, Piccinini L, De Pasquale A and Ascari E (1994) Treatment of multiple myeloma according to extension of disease: a prospective, randomized study comparing a less with a more aggressive cytostatic policy. Br J Cancer 70: 1203–1210

    CAS  Article  PubMed Central  Google Scholar 

  • Van de Berg BC, Lecouvet FE, Michaux L, Labaisse M, Malghem J, Jamart J, Maldague BE, Ferrant A and Michaux JL (1996) Stage I multiple myeloma: value of MR imaging of the bone marrow in the determination of prognosis. Radiology 20: 243–246

    Article  Google Scholar 

  • Vesole DH, Tricot G, Jagannath S, Desikan KR, Siegel D, Dwayne B, Miller L, Cheson B, Crowley J and Barlogie B (1996) Autotransplants in multiple myeloma: what have we learned? Blood 88: 838–847

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

The following centres also participated in this study: Medicina I, Ospedale di Alessandria (Dr A Pagetto); Medicina I, Ospedale di Melegnano (Prof G Santagati); Medicina I, Ospedale di Gallarate (Dr A Ceriani); Cattedra di Ematologia, Università di Parma (Dr G Dotti); Medicina B, Ospedale di Biella (Dr M Badone); Medicina Generale, Ospedale di Somma Lombardo (Dr A Daverio); Medicina C, Ospedale di Varese (Dr N Brumana); Medicina A, Ospedale di Varese (Dr G Pinotti)

Rights and permissions

From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/

Reprints and Permissions

About this article

Cite this article

Riccardi, A., Mora, O., Tinelli, C. et al. Long-term survival of stage I multiple myeloma given chemotherapy just after diagnosis or at progression of the disease: a multicentre randomized study. Br J Cancer 82, 1254–1260 (2000). https://doi.org/10.1054/bjoc.1999.1087

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1054/bjoc.1999.1087

Keywords

  • multiple myeloma
  • stage I
  • early or delayed treatment
  • survival

Further reading

Search

Quick links