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Post-transplant consolidation therapy using thalidomide alone for the patients with multiple myeloma: a feasibility study in Japanese population

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Abstract

In order to test for improved survival following autologous transplantation (ASCT), we conducted a prospective clinical trial of post-ASCT thalidomide therapy in Japanese patients with multiple myeloma (MM). Twenty-five newly diagnosed patients received double or single ASCT with high-dose melphalan (200 mg/m2). Two months after stem cell infusion, if the patients failed to achieve a near-complete response, thalidomide was administered at 200 mg/day until disease progression or occurrence of intolerable adverse events. Seventeen patients were in partial response or minimal response after ASCT and received thalidomide alone. Their median progression-free survival (PFS) from ASCT was 17.4 months, and the median overall survival (OS) was 42.9 months. Some patients with normal karyotype experienced durable disease stabilization for over 5 years. Five patients who exhibited high-risk chromosomal changes such as t(4;14) or deletion of chromosome 13 or 17 showed very short PFS and OS compared with those who did not. Observed grade 3 or 4 toxicities included infection in three patients, hematological toxicities in three, and gastrointestinal toxicities in two, but there was no grade 3 or higher peripheral neuropathy, probably due to appropriate dose modifications. This long-term prospective study is the first to demonstrate the feasibility of post-ASCT thalidomide therapy in Japanese patients with MM.

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References

  1. Attal M, Harousseau JL, Stoppa AM, Sotto JJ, Fuzibet JG, Rossi JF, Casassus P, Maisonneuve H, Facon T, Ifrah N, Payen C, Bataille R. A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe Français du Myélome. N Engl J Med. 1996;335:91–7.

    Article  PubMed  CAS  Google Scholar 

  2. Child JA, Morgan GJ, Davies FE, et al. High-dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma. N Engl J Med. 2003;348:1875–83.

    Article  PubMed  CAS  Google Scholar 

  3. The Myeloma Trialists’ Collaborative Group. Interferon as therapy for multiple myeloma: an individual patient data overview of 24 randomized trials and 4012 patients. Br J Haematol. 2001;113:1020–34.

    Article  Google Scholar 

  4. Fritz E, Ludwig H. Interferon-alpha treatment in multiple myeloma: meta-analysis of 30 randomised trials among 3948 patients. Ann Oncol. 2000;11:1427–36.

    Article  PubMed  CAS  Google Scholar 

  5. Attal M, Harousseau JL, Leyvraz S, et al. Maintenance therapy with thalidomide improves survival in patients with multiple myeloma. Blood. 2006;108:3289–94.

    Article  PubMed  CAS  Google Scholar 

  6. Barlogie B, Tricot G, Anaissie E, et al. Thalidomide and hematopoietic-cell transplantation for multiple myeloma. N Engl J Med. 2006;354:1021–30.

    Article  PubMed  CAS  Google Scholar 

  7. Lokhorst HM, van der Holt B, Zweegman S, et al. A randomized phase 3 study on the effect of thalidomide combined with adriamycin, dexamethasone, and high-dose melphalan, followed by thalidomide maintenance in patients with multiple myeloma. Blood. 2010;115:1113–20.

    Article  PubMed  CAS  Google Scholar 

  8. Spencer A, Prince HM, Roberts AW, et al. Consolidation therapy with low-dose thalidomide and prednisolone prolongs the survival of multiple myeloma patients undergoing a single autologous stem-cell transplantation procedure. J Clin Oncol. 2009;27:1788–93.

    Article  PubMed  CAS  Google Scholar 

  9. Morgan G, Gregory WM, Davies FE, et al. The role of maintenance thalidomide therapy in multiple myeloma: MRC myeloma IX results and meta-analysis. Blood. 2012;119:7–15.

    Article  PubMed  CAS  Google Scholar 

  10. Attal M, Lauwers-Cances V, Marit G, et al. Lenalidomide after stem-cell transplantation for multiple myeloma. N Engl J Med. 2012;366:1782–91.

    Article  PubMed  CAS  Google Scholar 

  11. McCarthy P, Owzar K, Hofmeister CC, et al. Lenalidomide after stem-cell transplantation for multiple myeloma. N Engl J Med. 2012;366:1770–81.

    Article  PubMed  CAS  Google Scholar 

  12. Sonneveld P, Schmidt-Wolf I, van der Holt B, et al. Hovon-65/GMMG-HD4 randomized phase III trial comparing bortezomib, doxorubicin, dexamethasone (PAD) vs VAD followed by high-dose melphalan and maintenance with bortezomib or thalidomide in patients with newly diagnosed multiple myeloma. Blood 2010; 116:[abstract] 40.

    Google Scholar 

  13. Bladé J, Samson D, Reece D, Apperley J, Björkstrand B, Gahrton G, Gertz M, Giralt S, Jagannath S, Vesole D. Criteria for evaluating disease response and progression in patients with multiple myeloma treated by high-dose therapy and haemopoietic stem cell transplantation. Myeloma Subcommittee of the EBMT. European Group for Blood and Marrow Transplant. Br J Haematol. 1998;102:1115–23.

    Article  PubMed  Google Scholar 

  14. Tsukada Y, Hattori Y, Nakajima H, et al. B-cell acute lymphoblastic leukemia developed 5 years after autologous stem cell transplantation for multiple myeloma. Rinsho Ketsueki. 2012;53:219–23.

    PubMed  Google Scholar 

  15. Moreau P, Avet-Loiseau H, Harousseau J-L, et al. Current trends in autologous stem-cell transplantation for myeloma in the era of novel agents. J Clin Oncol. 2011;29:1898–906.

    Article  PubMed  Google Scholar 

  16. Boyd KD, Ross FM, Chiecchio L, et al. A novel prognostic model in myeloma based on co-segregating adverse FISH lesions and the ISS: analysis of patients treated in the MRC Myeloma IX trial. Leukemia. 2012;26:349–55.

    Article  PubMed  CAS  Google Scholar 

  17. Barlogie B, Pineda-Roman M, van Rhee F, et al. Thalidomide arm of Total Therapy 2 improves complete remission duration and survival in myeloma patients with metaphase cytogenetic abnormalities. Blood. 2008;112:3115–21.

    Article  PubMed  CAS  Google Scholar 

  18. Hattori Y, Okamoto S, Shimada N, et al. Single-institute phase 2 study of thalidomide treatment for refractory or relapsed multiple myeloma: prognostic factors and unique toxicity profile. Cancer Sci. 2008;99:1243–50.

    Article  PubMed  CAS  Google Scholar 

  19. Du W, Hattori Y, Yamada T, et al. NK4, an antagonist of hepatocyte growth factor, inhibits growth of multiple myeloma cells in vivo; molecular targeting of angiogenic growth factor. Blood. 2007;109:3042–9.

    Article  PubMed  CAS  Google Scholar 

  20. Delforge M, Bladé J, Dimopoulos MA, Facon T, Kropff M, Ludwig H, Palumbo A, Van Damme P, San-Miguel JF, Sonneveld P. Treatment-related peripheral neuropathy in multiple myeloma: the challenge continues. Lancet Oncol. 2010;11:1086–95.

    Article  PubMed  CAS  Google Scholar 

  21. Vickrey E, Allen S, Mehta J, Singhal S. Acyclovir to prevent reactivation of varicella zoster virus (herpes zoster) in multiple myeloma patients receiving bortezomib therapy. Cancer. 2009;115:229–32.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We would like to acknowledge Drs. H. Uchida (Tokyo Electric Power Company Hospital), S. Hagiwara and A. Miwa (National Center for Global Health and Medicine Hospital) for their referral of patients. This work was supported in part by a grant from the Japanese Foundation for Multidisciplinary Treatment of Cancer (Y.H.), by a Grant-in-Aid for Scientific Research (Y.H.) and a grant from the Private University Strategic Research Base Development Program of MEXT (Y.H.) from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and by the Japan Leukemia Research Fund (Y.H.).

Conflict of interest

There is no conflict of interest regarding this manuscript to be disclosed.

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Authors and Affiliations

  1. Division of Hematology, Department of Medicine, Keio University School of Medicine, Tokyo, Japan

    Tomoki Ueda, Kenji Yokoyama, Shinichiro Okamoto, Yuiko Tsukada, Jo Ishizawa, Eri Matsuki, Yasuo Ikeda & Yutaka Hattori

  2. Division of Hematology, Saiseikai Central Hospital, Tokyo, Japan

    Yuiko Tsukada, Yasuo Ikeda & Yutaka Hattori

  3. Division of Clinical Physiology and Therapeutics, Keio University Faculty of Pharmacy, 1-5-30 Shiba-koen, Minato-ku, Tokyo, 105-8512, Japan

    Rioko Iino & Yutaka Hattori

  4. Department of Preventive Medicine and Public Health, Keio University School of Medicine, Tokyo, Japan

    Keiko Asakura

  5. Department of Life Science and Medical Bioscience, School of Advanced Science and Engineering, Waseda University, Tokyo, Japan

    Yasuo Ikeda

Authors
  1. Tomoki Ueda
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  2. Rioko Iino
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  3. Kenji Yokoyama
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  7. Jo Ishizawa
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  9. Yasuo Ikeda
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  10. Yutaka Hattori
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Correspondence to Yutaka Hattori.

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Ueda, T., Iino, R., Yokoyama, K. et al. Post-transplant consolidation therapy using thalidomide alone for the patients with multiple myeloma: a feasibility study in Japanese population. Int J Hematol 96, 477–484 (2012). https://doi.org/10.1007/s12185-012-1166-y

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  • DOI: https://doi.org/10.1007/s12185-012-1166-y

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