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.

  • Original Article
  • Published:

Autografting

Pilot study of 13cis-retinoic acid+dexamethasone+alpha interferon as maintenance therapy following high-dose chemotherapy and autologous stem cell transplant for multiple myeloma

Bone Marrow Transplantation volume 35, pages 979–984 (2005)Cite this article

Summary:

Interleukin 6 (IL-6) is a major growth factor for myeloma cells and retinoids have been shown to inhibit expression of the interleukin 6 receptor (IL-6R). We performed a pilot study to assess the efficacy and tolerability of 13cis retinoic acid (13cRA) and dexamethasone (Dex), when added to interferon α (IFNα) as maintenance therapy post autologous stem cell transplantation. Between 90 and 120 days post stem cell transplantation, 33 patients were started on 13cRA 1 mg/kg p.o. daily for 14 days and Dex 40 mg p.o daily for 5 days every month. 13cRA was dose escalated by 0.5 mg/kg/month to 2 mg/kg. Seventeen patients had a persistent paraprotein post transplant. Overall, a response to therapy was observed in 11/17 (64%), with a complete response in 4/17 (23.5%) and a partial response (⩾50% paraprotein decline) in 7/17 (41%). With a median follow-up of 34.8 months, 22/33 (66%) demonstrated disease progression and 11/33 (33%) died. The median progression-free survival from diagnosis was 34.7 months. Although a decline in paraprotein was frequently observed on triple therapy, many patients discontinued therapy due to the side-effects of the IFNα. Future trials should be designed using 13cRA and Dex alone.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

References

  1. Attal M, Harousseau JL, Stoppa AM et al. A prospective randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. N Engl J Med 1996; 335: 91–97.

    Article  CAS  Google Scholar 

  2. Child JA, Morgan GJ, Davies FE et al. High-dose chemotherapy with hematopoeitic stem-cell rescue for multiple myeloma. N Engl J Med 2003; 348: 1875–1883.

    Article  CAS  Google Scholar 

  3. Cunningham D, Powles R, Malpas J et al. A randomized trial of maintenance interferon following high-dose chemotherapy in multiple myeloma: long-term follow-up results. Br J Haematol 1998; 102: 495–502.

    Article  CAS  Google Scholar 

  4. Kawano M, Hirano T, Matsuda T et al. Autocrine generation and requirement of BSF-2/IL-6 for human multiple myelomas. Nature 1988; 332: 83–85.

    Article  CAS  Google Scholar 

  5. Kawano M, Tanaka H, Ishikawa H et al. Interleukin-1 accelerates autocrine growth of myeloma cells through interleukin-6 in human myeloma. Blood 1989; 73: 2145–2148.

    CAS  PubMed  Google Scholar 

  6. Sidell N, Taga T, Hirano T et al. Retinoic acid-induced growth inhibition of a human myeloma cell line via down regulation of IL-6 receptors. J Immunol 1991; 146: 3809–3814.

    CAS  PubMed  Google Scholar 

  7. Levy Y, Labaume S, Colombel M et al. Retinoic acid modulates the in vivo and in vitro growth of IL-6 autocrine human myeloma cells via induction of apoptosis. Clin Exp Immunol 1996; 104: 167–172.

    Article  CAS  Google Scholar 

  8. Ogata A, Nishimoto N, Shima Y et al. Inhibitory effect of all-trans retinoic acid on the growth of freshly isolated myeloma cells via interference with interleukin-6 signal transduction. Blood 1994; 84: 3040–3046.

    CAS  PubMed  Google Scholar 

  9. Musto P, Falcone A, Sajeva MR et al. All-trans retinoic acid for advanced multiple myeloma. Blood 1995; 85: 3769–3770.

    CAS  PubMed  Google Scholar 

  10. Musto P, Sajeva M, Sanpaolo G et al. All-trans retinoic acid in combination with alpha-interferon and dexamethasone for advanced multiple myeloma. Haematologica 1995; 82: 354–356.

    Google Scholar 

  11. Palumbo A, Battaglio S, Napoli P et al. Retinoic acid inhibits the growth of human myeloma cells in vitro. Br J Haematol 1995; 89: 555–560.

    Article  CAS  Google Scholar 

  12. Chen Y, Desai P, Shiao R et al. Inhibition of myeloma cell growth by dexamethasone and all-trans retinoic acid: synergy through modulation of interleukin-6 autocrine loop at multiple sites. Blood 1996; 87: 314–323.

    CAS  PubMed  Google Scholar 

  13. Blade J, Samson D, Reece D et al. Criteria for evaluating disease response and progression in patients with multiple myeloma treated by high-dose therapy and haematopoietic stem cell transplantation. Br J Haematol 1998; 102: 1115–1123.

    Article  CAS  Google Scholar 

  14. The Nordic Myeloma Group. Interferon-alpha2b added to melphalan-prednisone for initial and maintenance therapy in multiple myeloma. Ann Intern Med 1996; 124: 212–222.

    Article  CAS  Google Scholar 

  15. Singhal S, Powles R, Milan S et al. Kinetics of paraprotein clearence after autografting for multiple myeloma. Bone Marrow Transplant 1995; 16: 537–540.

    CAS  Google Scholar 

  16. Alexanian R, Dimopolous MA, Delasalle K et al. Primary dexamethasone treatment of multiple myeloma. Blood 1992; 80: 887–890.

    CAS  Google Scholar 

  17. Browman GP, Bergsagel D, Sicheri D et al. Randomized trial of interferon maintenance in multiple myeloma: a study of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 1995; 13: 2354–2360.

    Article  CAS  Google Scholar 

  18. Mandelli F, Avvisati G, Amadori S et al. Maintenance treatment with recombinant interferon alpha-2b in patients with multiple myeloma responding to conventional induction chemotherapy. N Engl J Med 1990; 322: 1430–1434.

    Article  CAS  Google Scholar 

  19. Westin J, Rodjer S, Turesson I et al. Interferon alfa-2b vs no maintenance therapy during the plateau phase in multiple myeloma: a randomized study. Cooperative study group. Br J Haematol 1995; 89: 561–568.

    Article  CAS  Google Scholar 

  20. Attal M, Harousseau JL, Facon T et al. Single vs double autologous stem-cell transplantation for multiple myeloma. N Engl J Med 2003; 349: 2495–2502.

    Article  CAS  Google Scholar 

  21. Berenson J, Crowley J, Grogan TM et al. Maintenance therapy with alternate-day prednisone improves survival in multiple myeloma patients. Blood 2002; 99: 3163–3168.

    Article  CAS  Google Scholar 

  22. Salmon SE, Crowley JJ, Balcerzak SP et al. Interferon vs interferon plus prednisone remission maintenance therapy for multiple myeloma: a Southwest Oncology Group Study. J Clin Oncol 1998; 16: 890–896.

    Article  CAS  Google Scholar 

  23. Toma S, Bonelli L, Sartoris A et al. 13 cis retinoic acid in head and neck cancer chemoprevention: results of a randomized trial from the Italian Head and Neck Chemoprevention Study Group. Oncol Rep 2004; 6: 1297–1307.

    Google Scholar 

  24. Lippman SM, Lee JJ, Karp DD et al. Randomized phase III intergroup trial of isotretinoin to prevent secondary and primary tumors in stage I non-small cell lung cancer. J Natl Cancer Inst 2001; 93: 605–618.

    Article  CAS  Google Scholar 

  25. Barlogie B, Kyle R, Anderson K et al. Comparable survival in multiple myeloma with high dose chemotherapy employing MEL 140 mg/m+TBI 12 Gy autotransplants vs standard dose therapy with VBMCP and no benefit from interferon maintenance: results of Intergroup Trial S9321 (abstract). Blood 2003; 102: 42a.

    Google Scholar 

Download references

Acknowledgements

We are grateful to Roche Pharmaceuticals who supplied both the 13cis retinoic acid and the interferon alpha for this study.

Author information

Authors and Affiliations

  1. Department of Internal Medicine, Barnes-Jewish Hospital, Washington University School of Medicine, Saint Louis, MO, USA

    J Friedman

  2. Department of Internal Medicine, Division of Oncology, Section of Bone Marrow Transplantation and Leukemia, Siteman Cancer Center and Washington University School of Medicine, Saint Louis, MO, USA

    H Khoury, D Adkins, S Devine, B Nervi, T Edwards, J DiPersio & R Vij

Authors
  1. J Friedman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. H Khoury
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. D Adkins
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S Devine
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. B Nervi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. T Edwards
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. J DiPersio
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. R Vij
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to R Vij.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Friedman, J., Khoury, H., Adkins, D. et al. Pilot study of 13cis-retinoic acid+dexamethasone+alpha interferon as maintenance therapy following high-dose chemotherapy and autologous stem cell transplant for multiple myeloma. Bone Marrow Transplant 35, 979–984 (2005). https://doi.org/10.1038/sj.bmt.1704937

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1704937

Keywords

Search

Advanced search

Quick links