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Plasma Cell Disorders

The impact of induction regimen on transplant outcome in newly diagnosed multiple myeloma in the era of novel agents

Bone Marrow Transplantation volume 52, pages 34–40 (2017)Cite this article

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Abstract

We compared overall survival (OS) of 1017 patients with newly diagnosed multiple myeloma (MM) who were treated with different novel agent-based induction regimens and who underwent early autologous stem cell transplant (ASCT). Subgroups were defined by type of induction therapy: cyclophosphamide–bortezomib–dexamethasone (CyBorD; n=193), bortezomib–dexamethasone (Vd; n=64), lenalidomide–dexamethasone (Rd; n=251), bortezomib–lenalidomide–dexamethasone (VRd; n=126), thalidomide–dexamethasone (Td; n=155) and vincristine–doxorubicin–dexamethasone or dexamethasone alone (VAD/Dex; n=228). The median follow-up of the surviving patients was 66.7 months. The 5-year OS rates with CyBorD, Vd, Rd, VRd, Td and VAD/Dex were 79.2%, 72.3%, 79.2%, 79.0%, 57.4% and 63.4%, respectively (log-rank, P<0.001). In a multivariate analysis, after controlling for important patient and disease variables, VRd had a superior OS compared with CyBorD (hazard ratio (HR), 0.32; 95% confidence interval (CI), 0.10–0.88; P=0.03) and Vd (HR, 0.16; 95% CI, 0.04–0.52; P=0.002). In conclusion, our study demonstrates that among patients completing induction therapy and continuing to early transplant, VRd induction leads to improved OS compared with CyBorD and Vd regimens.

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References

  1. SEER Cancer Statistics Factsheets: myeloma. National Cancer Institute: Bethesda, MD [cited 4 January 2016]. Available from http://seer.cancer.gov/statfacts/html/mulmy.html.

  2. Manikkam Umakanthan J, Uprety D, Kasireddy V . Analyzing survival trends in multiple myeloma patients in pre and post-bortezomib era using the SEER database. Blood 2014; 124: (abstract 2639).

    Google Scholar 

  3. Moreau P, Attal M, Facon T . Frontline therapy of multiple myeloma. Blood 2015; 125: 3076–3084.

    Article  CAS  Google Scholar 

  4. 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 Français du Myélome. N Engl J Med 1996; 335: 91–97.

    Article  CAS  Google Scholar 

  5. 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  Google Scholar 

  6. Cavallo F, Spencer A, Gay F, Hajek R, Petrucci MT, Ben Yahuda D et al. Early autologous stem cell transplantation improves survival in newly diagnosed multiple myeloma patients. Haematologica 2014; 99: 408–416.

    Article  Google Scholar 

  7. Hashmi S, Pandya C, Gertz MA, Dispenzieri A, Hogan W, Siddiqui MA et al. Cost effectiveness decision tree analysis of early versus late autologous stem cell transplantation (ASCT) in multiple myeloma (MM) in the United States (US) [abstract]. Blood 2012; 120: 602.

    Google Scholar 

  8. National Comprehensive Cancer Network NCCN Guidelines: multiple myeloma. National Comprehensive Cancer Network: Fort Washington, PA, c2016 [cited January 2016]. Available from http://www.nccn.org/professionals/physician_gls/f_guidelines.asp#myeloma.

  9. Moreau P, San Miguel J, Ludwig H, Schouten H, Mohty M, Dimopoulos M et al. Multiple myeloma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2013; 24 (Suppl 6): vi133–vi137.

    Article  Google Scholar 

  10. Cavo M, Rajkumar SV, Palumbo A, Moreau P, Orlowski R, Blade J et al. International Myeloma Working Group consensus approach to the treatment of multiple myeloma patients who are candidates for autologous stem cell transplantation. Blood 2011; 117: 6063–6073.

    Article  CAS  Google Scholar 

  11. Gertz MA, Dingli D . How we manage autologous stem cell transplantation for patients with multiple myeloma. Blood 2014; 124: 882–890.

    Article  CAS  Google Scholar 

  12. Kaplan EL, Meier P . Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958; 53: 457–481.

    Article  Google Scholar 

  13. Harousseau JL, Attal M, Avet-Loiseau H, Marit G, Caillot D, Mohty M et al. Bortezomib plus dexamethasone is superior to vincristine plus doxorubicin plus dexamethasone as induction treatment prior to autologous stem-cell transplantation in newly diagnosed multiple myeloma: results of the IFM 2005-01 phase III trial. J Clin Oncol 2010; 28: 4621–4629.

    Article  CAS  Google Scholar 

  14. Kumar S, Flinn I, Richardson PG, Hari P, Callander N, Noga SJ et al. Randomized, multicenter, phase 2 study (EVOLUTION) of combinations of bortezomib, dexamethasone, cyclophosphamide, and lenalidomide in previously untreated multiple myeloma. Blood 2012; 119: 4375–4382.

    Article  CAS  Google Scholar 

  15. Leiba M, Kedmi M, Duek A, Freidman T, Weiss M, Leiba R et al. Bortezomib-cyclophosphamide-dexamethasone (VCD) versus bortezomib-thalidomide-dexamethasone (VTD)-based regimens as induction therapies in newly diagnosed transplant eligible patients with multiple myeloma: a meta-analysis. Br J Haematol 2014; 166: 702–710.

    Article  CAS  Google Scholar 

  16. Sonneveld P, Goldschmidt H, Rosinol L, Blade J, Lahuerta JJ, Cavo M et al. Bortezomib-based versus nonbortezomib-based induction treatment before autologous stem-cell transplantation in patients with previously untreated multiple myeloma: a meta-analysis of phase III randomized, controlled trials. J Clin Oncol 2013; 31: 3279–3287.

    Article  CAS  Google Scholar 

  17. Moreau P, Avet-Loiseau H, Facon T, Attal M, Tiab M, Hulin C et al. Bortezomib plus dexamethasone versus reduced-dose bortezomib, thalidomide plus dexamethasone as induction treatment before autologous stem cell transplantation in newly diagnosed multiple myeloma. Blood 2011; 118: 5752–5758.

    Article  CAS  Google Scholar 

  18. Cavo M, Tacchetti P, Patriarca F, Petrucci MT, Pantani L, Galli M et al. Bortezomib with thalidomide plus dexamethasone compared with thalidomide plus dexamethasone as induction therapy before, and consolidation therapy after, double autologous stem-cell transplantation in newly diagnosed multiple myeloma: a randomised phase 3 study. Lancet 2010; 376: 2075–2085.

    Article  CAS  Google Scholar 

  19. Durie B, Hoering A, Rajkumar SV, Abidi MH, Epstein J, Kahanic SP et al. Bortezomib, lenalidomide and dexamethasone vs. lenalidomide and dexamethasone in patients (Pts) with previously untreated multiple myeloma without an intent for immediate autologous stem cell transplant (ASCT): results of the randomized phase III trial SWOG S0777. Blood 2015; 126: (abstract 25).

    Google Scholar 

  20. Moreau P, Hulin C, Macro M, Caillot D, Chaleteix C, Roussel M et al. Bortezomib, thalidomide and dexamethasone (VTD) is superior to bortezomib, cyclophosphamide and dexamethasone (VCD) prior to autologous stem cell transplantation for patients with de novo multiple myeloma: results of the prospective IFM 2013-14 trial. Blood 2015; 126: 393.

    Article  Google Scholar 

  21. Rosinol L, Oriol A, Teruel AI, Hernandez D, Lopez-Jimenez J, de la Rubia J et al. Superiority of bortezomib, thalidomide, and dexamethasone (VTD) as induction pretransplantation therapy in multiple myeloma: a randomized phase 3 PETHEMA/GEM study. Blood 2012; 120: 1589–1596.

    Article  CAS  Google Scholar 

  22. Hoering A, Crowley J, Shaughnessy JD Jr, Hollmig K, Alsayed Y, Szymonifka J et al. Complete remission in multiple myeloma examined as time-dependent variable in terms of both onset and duration in total therapy protocols. Blood 2009; 114: 1299–1305.

    Article  CAS  Google Scholar 

  23. Harousseau JL, Avet-Loiseau H, Attal M, Charbonnel C, Garban F, Hulin C et al. Achievement of at least very good partial response is a simple and robust prognostic factor in patients with multiple myeloma treated with high-dose therapy: long-term analysis of the IFM 99-02 and 99-04 Trials. J Clin Oncol 2009; 27: 5720–5726.

    Article  CAS  Google Scholar 

  24. Gay F, Larocca A, Wijermans P, Cavallo F, Rossi D, Schaafsma R et al. Complete response correlates with long-term progression-free and overall survival in elderly myeloma treated with novel agents: analysis of 1175 patients. Blood 2011; 117: 3025–3031.

    Article  CAS  Google Scholar 

  25. Martinez-Lopez J, Blade J, Mateos MV, Grande C, Alegre A, Garcia-Larana J et al. Long-term prognostic significance of response in multiple myeloma after stem cell transplantation. Blood 2011; 118: 529–534.

    Article  CAS  Google Scholar 

  26. Durie BG, Harousseau JL, Miguel JS, Blade J, Barlogie B, Anderson K et al. International uniform response criteria for multiple myeloma. Leukemia 2006; 20: 1467–1473.

    Article  CAS  Google Scholar 

  27. Kapoor P, Kumar SK, Dispenzieri A, Lacy MQ, Buadi F, Dingli D et al. Importance of achieving stringent complete response after autologous stem-cell transplantation in multiple myeloma. J Clin Oncol 2013; 31: 4529–4535.

    Article  Google Scholar 

  28. Martinez-Lopez J, Paiva B, Lopez-Anglada L, Mateos MV, Cedena T, Vidriales MB et al. Critical analysis of the stringent complete response in multiple myeloma: contribution of sFLC and bone marrow clonality. Blood 2015; 126: 858–862.

    Article  CAS  Google Scholar 

  29. de Tute RM, Rawstron AC, Gregory WM, Child JA, Davies FE, Bell SE et al. Minimal residual disease following autologous stem cell transplant in myeloma: impact on outcome is independent of induction regimen. Haematologica 2016; 101: e69–e71.

    Article  CAS  Google Scholar 

  30. Mohty M, Richardson PG, McCarthy PL, Attal M . Consolidation and maintenance therapy for multiple myeloma after autologous transplantation: where do we stand? Bone Marrow Transplant 2015; 50: 1024–1029.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Division of Hematology, Mayo Clinic, Rochester, MN, USA

    R Chakraborty, E Muchtar, S Kumar, F K Buadi, D Dingli, A Dispenzieri, S R Hayman, W J Hogan, P Kapoor, M Q Lacy & M A Gertz

  2. Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA

    N Leung

  3. Hospitalist Services, Essentia Health-St. Joseph's Medical Center, Brainerd, MN, USA

    R Chakraborty

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  1. R Chakraborty
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  2. E Muchtar
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  12. M A Gertz
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Corresponding author

Correspondence to M A Gertz.

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Competing interests

S Kumar: Celgene (Consultancy and Research Funding), Millennium (Consultancy and Research Funding), Novartis (Research Funding), Onyx (Consultancy and Research Funding), AbbVie (Research Funding), Janssen (Consultancy and Research Funding) and BMS (Consultancy and Research Funding); A Dispenzieri: research funding (Celgene, Millennium, Pfizer and Janssen) and travel grant (Pfizer); P Kapoor: research funding from Millennium (Takeda), Celgene and Onyx (Amgen); MQ Lacy: research funding (Celgene); MA Gertz: Celgene (Honoraria), Millenium (Consultancy and Honoraria), Onyx (Honoraria), Novartis (Honoraria) and Smith Kline (Honoraria). The remaining authors declare no conflict of interest.

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Presented at the American Society of Hematology (ASH) 57th Annual Meeting and Exposition, Orlando, Florida, 5–8 December 2015.

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Chakraborty, R., Muchtar, E., Kumar, S. et al. The impact of induction regimen on transplant outcome in newly diagnosed multiple myeloma in the era of novel agents. Bone Marrow Transplant 52, 34–40 (2017). https://doi.org/10.1038/bmt.2016.214

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