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Autografting

Impact of pretransplant therapy in patients with newly diagnosed myeloma undergoing autologous SCT

Bone Marrow Transplantation volume 41, pages 1013–1019 (2008)Cite this article

Abstract

Autologous SCT (ASCT) remains an effective therapy for eligible patients with myeloma. Previous studies have suggested a lack of impact of the initial therapy on the outcome after ASCT. It is not clear if incorporation of new agents in the initial treatment regimens will have any impact on the outcome after ASCT. We studied 472 patients undergoing ASCT within 12 months of diagnosis to assess the effect of initial therapy on the outcome after ASCT. Patients received initial therapy with vincristine, adriamycin and dexamethasone (VAD), dexamethasone, thalidomide and dexamethasone or lenalidomide and dexamethasone. While patients treated with dexamethasone alone had higher disease burden at ASCT, no differences were observed in the response rates to ASCT, post transplant complications or treatment-related mortality among the groups. The median time to progression after ASCT was 27.1, 24.7, 21.1 months and did not reach the VAD, Dex, Thal–Dex and Len–Dex group, respectively, P=0.11. The median overall survival from ASCT was 62 months for VAD, 69.6 months for Dex and were not reached for Thal–Dex and Len–Dex groups, P=0.2. For patients undergoing early ASCT for myeloma, the nature of initial treatment utilized has no long-term impact on the outcome of ASCT.

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References

  1. Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ . Cancer statistics, 2007. CA Cancer J Clin 2007; 57: 43–66.

    Article  PubMed  Google Scholar 

  2. Attal M, Harousseau JL, Stoppa AM, Sotto JJ, Fuzibet JG, Rossi JF et al. A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. Intergroupe Francais du Myelome. N Engl J Med 1996; 335: 91–97.

    Article  CAS  PubMed  Google Scholar 

  3. Child JA, Morgan GJ, Davies FE, Owen RG, Bell SE, Hawkins K et al. High-dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma. N Engl J Med 2003; 348: 1875–1883.

    Article  CAS  PubMed  Google Scholar 

  4. Fermand JP, Ravaud P, Chevret S, Divine M, Leblond V, Belanger C et al. High-dose therapy and autologous peripheral blood stem cell transplantation in multiple myeloma: up-front or rescue treatment? Results of a multicenter sequential randomized clinical trial. Blood 1998; 92: 3131–3136.

    CAS  PubMed  Google Scholar 

  5. Barlogie B, Kyle RA, Anderson KC, Greipp PR, Lazarus HM, Hurd DD et al. Standard chemotherapy compared with high-dose chemoradiotherapy for multiple myeloma: final results of phase III US Intergroup Trial S9321. J Clin Oncol 2006; 24: 929–936.

    Article  CAS  PubMed  Google Scholar 

  6. Singhal S, Powles R, Sirohi B, Treleaven J, Kulkarni S, Mehta J . Response to induction chemotherapy is not essential to obtain survival benefit from high-dose melphalan and autotransplantation in myeloma. Bone Marrow Transplant 2002; 30: 673–679.

    Article  CAS  PubMed  Google Scholar 

  7. Kumar S, Lacy MQ, Dispenzieri A, Rajkumar SV, Fonseca R, Geyer S et al. High-dose therapy and autologous stem cell transplantation for multiple myeloma poorly responsive to initial therapy. Bone Marrow Transplant 2004; 34: 161–167.

    Article  CAS  PubMed  Google Scholar 

  8. Alexanian R, Dimopoulos MA, Delasalle KB, Hester J, Champlin R . Myeloablative therapy for primary resistant multiple myeloma. Stem Cells 1995; 13 (Suppl 2): 118–121.

    PubMed  Google Scholar 

  9. Vesole DH, Crowley JJ, Catchatourian R, Stiff PJ, Johnson DB, Cromer J et al. High-dose melphalan with autotransplantation for refractory multiple myeloma: results of a Southwest Oncology Group phase II trial. J Clin Oncol 1999; 17: 2173–2179.

    Article  CAS  PubMed  Google Scholar 

  10. Rajkumar SV, Blood E, Vesole D, Fonseca R, Greipp PR . Phase III clinical trial of thalidomide plus dexamethasone compared with dexamethasone alone in newly diagnosed multiple myeloma: a clinical trial coordinated by the Eastern Cooperative Oncology Group. J Clin Oncol 2006; 24: 431–436.

    Article  CAS  PubMed  Google Scholar 

  11. Rajkumar SV, Hayman SR, Lacy MQ, Dispenzieri A, Geyer SM, Kabat B et al. Combination therapy with lenalidomide plus dexamethasone (Rev/Dex) for newly diagnosed myeloma. Blood 2005; 106: 4050–4053.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Richardson PG, Barlogie B, Berenson J, Singhal S, Jagannath S, Irwin D et al. A phase 2 study of bortezomib in relapsed, refractory myeloma. N Engl J Med 2003; 348: 2609–2617.

    Article  CAS  PubMed  Google Scholar 

  13. Richardson PG, Sonneveld P, Schuster MW, Irwin D, Stadtmauer EA, Facon T et al. Bortezomib or high-dose dexamethasone for relapsed multiple myeloma. N Engl J Med 2005; 352: 2487–2498.

    Article  CAS  PubMed  Google Scholar 

  14. Jagannath S, Durie BG, Wolf J, Camacho E, Irwin D, Lutzky J et al. Bortezomib therapy alone and in combination with dexamethasone for previously untreated symptomatic multiple myeloma. Br J Haematol 2005; 129: 776–783.

    Article  CAS  PubMed  Google Scholar 

  15. Rajkumar SV, Jacobus S, Callander N, Fonseca R, Vesole D, Williams M et al. Phase III trial of lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone in newly diagnosed multiple myeloma (E4A03): a trial coordinated by the Eastern Cooperative Oncology Group. J Clin Oncol, Annual Meeting Abstracts 2007; 25 (Suppl 18): LBA8025.

    Google Scholar 

  16. Lacy MQ, Gertz MA, Dispenzieri A, Hayman SR, Geyer S, Kabat B et al. Long-term results of response to therapy, time to progression, and survival with lenalidomide plus dexamethasone in newly diagnosed myeloma. Mayo Clin Proc 2007; 82: 1179–1184.

    Article  CAS  PubMed  Google Scholar 

  17. Barlogie B, Smith L, Alexanian R . Effective treatment of advanced multiple myeloma refractory to alkylating agents. N Engl J Med 1984; 310: 1353–1356.

    Article  CAS  PubMed  Google Scholar 

  18. Greipp PR, Lust JA, O’Fallon WM, Katzmann JA, Witzig TE, Kyle RA . Plasma cell labeling index and beta 2-microglobulin predict survival independent of thymidine kinase and C-reactive protein in multiple myeloma. Blood 1993; 81: 3382–3387.

    CAS  PubMed  Google Scholar 

  19. Blade J, Samson D, Reece D, Apperley J, Bjorkstrand B, Gahrton G et al. 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: 1115–1123.

    Article  CAS  PubMed  Google Scholar 

  20. Kaplan E, Meier P . Non-parametric estimation from incomplete observations. J Am Stat Assoc 1958; 53: 457–481.

    Article  Google Scholar 

  21. Cox D . Regression models and life tables. J R Stat Soc 1972; 34: 187–202.

    Google Scholar 

  22. Dingli D, Nowakowski GS, Dispenzieri A, Lacy MQ, Hayman S, Litzow MR et al. Cyclophosphamide mobilization does not improve outcome in patients receiving stem cell transplantation for multiple myeloma. Clin Lymphoma Myeloma 2006; 6: 384–388.

    Article  CAS  PubMed  Google Scholar 

  23. Moreau P, Facon T, Attal M, Hulin C, Michallet M, Maloisel F et al. Comparison of 200 mg/m(2) melphalan and 8 Gy total body irradiation plus 140 mg/m(2) melphalan as conditioning regimens for peripheral blood stem cell transplantation in patients with newly diagnosed multiple myeloma: final analysis of the Intergroupe Francophone du Myelome 9502 randomized trial. Blood 2002; 99: 731–735.

    Article  CAS  PubMed  Google Scholar 

  24. Knudsen LM, Rasmussen T, Jensen L, Johnsen HE . Reduced bone marrow stem cell pool and progenitor mobilisation in multiple myeloma after melphalan treatment. Med Oncol 1999; 16: 245–254.

    Article  CAS  PubMed  Google Scholar 

  25. Kumar S, Lacy MQ, Dispenzieri A, Rajkumar SV, Fonseca R, Geyer S et al. Single agent dexamethasone for pre-stem cell transplant induction therapy for multiple myeloma. Bone Marrow Transplant 2004; 34: 485–490.

    Article  CAS  PubMed  Google Scholar 

  26. Segeren CM, Sonneveld P, van der Holt B, Baars JW, Biesma DH, Cornellissen JJ et al. Vincristine, doxorubicin and dexamethasone (VAD) administered as rapid intravenous infusion for first-line treatment in untreated multiple myeloma. Br J Haematol 1999; 105: 127–130.

    Article  CAS  PubMed  Google Scholar 

  27. Alexanian R, Dimopoulos MA, Delasalle K, Barlogie B . Primary dexamethasone treatment of multiple myeloma. Blood 1992; 80: 887–890.

    CAS  PubMed  Google Scholar 

  28. Rajkumar SV, Hussein M, Catalano J, Jedrzejcak W, Sirkovich S, Olesnyckyj M et al. A randomized, double-blind, placebo-controlled trial of thalidomide plus dexamethasone versus dexamethasone alone as primary therapy for newly diagnosed multiple myeloma. Am Soc Hematol, Annual Meeting Abstracts 2006; 108: 795.

    Google Scholar 

  29. Cavo M, Zamagni E, Tosi P, Tacchetti P, Cellini C, Cangini D et al. Superiority of thalidomide and dexamethasone over vincristine-doxorubicin-dexamethasone (VAD) as primary therapy in preparation for autologous transplantation for multiple myeloma. Blood 2005; 106: 35–39.

    Article  CAS  PubMed  Google Scholar 

  30. Macro M, Divine M, Uzunhan Y, Jaccard A, Bouscary D, Leblond V et al. Dexamethasone+thalidomide (Dex/Thal) compared to VAD as a pre-transplant treatment in newly diagnosed multiple myeloma (mm): a randomized trial. Am Soc Hematol, Annual Meeting Abstracts 2006; 108: 57.

    Google Scholar 

  31. Rajkumar SV, Fonseca R, Dispenzieri A, Lacy MQ, Witzig TE, Lust JA et al. Effect of complete response on outcome following autologous stem cell transplantation for myeloma. Bone Marrow Transplant 2000; 26: 979–983.

    Article  CAS  PubMed  Google Scholar 

  32. Harousseau J-L, Attal M, Moreau P, Garban F, Facon T, Avet-Loiseau H . The prognostic impact of complete remission (CR) plus very good partial remission (VGPR) in a double-transplantation program for newly diagnosed multiple myeloma (MM). Combined results of the IFM 99 trials. Am Soc Hematol, Annual Meeting Abstracts 2006; 108: 3077.

    Google Scholar 

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Acknowledgements

This study was supported in part by Hematologic Malignancies Program, Mayo Clinic CR20 program, ASCO Young Investigator Award and Amgen Oncology Institute Junior Faculty Award (SK).

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Authors and Affiliations

  1. Department of Internal Medicine, Division of Hematology, Mayo Clinic, Rochester, MN, USA

    S K Kumar, D Dingli, A Dispenzieri, M Q Lacy, S R Hayman, F K Buadi, S V Rajkumar, M R Litzow & M A Gertz

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  1. S K Kumar
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Correspondence to S K Kumar.

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Kumar, S., Dingli, D., Dispenzieri, A. et al. Impact of pretransplant therapy in patients with newly diagnosed myeloma undergoing autologous SCT. Bone Marrow Transplant 41, 1013–1019 (2008). https://doi.org/10.1038/bmt.2008.24

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