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Myeloma

Stem cell mobilization in patients with newly diagnosed multiple myeloma after lenalidomide induction therapy

Leukemia volume 25, pages 1627–1631 (2011)Cite this article

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Abstract

Lenalidomide has raised concerns regarding its potential impact on the ability to collect stem cells for autologous stem cell transplantation, especially after prolonged exposure. The use of cyclophosphamide plus granulocyte colony-stimulating factor (G-CSF) to mobilize peripheral blood stem cells may overcome this concern. In newly diagnosed multiple myeloma (MM) patients, we investigated the influence of lenalidomide on stem cell collection. In a prospective study, 346 patients received four cycles of lenalidomide–dexamethasone (Rd). Stem cells were mobilized with cyclophosphamide and G-CSF. Patients failing to collect a minimum of 4 × 106 CD34+/kg cells received a second mobilization course. After mobilization, a median yield of 8.7 × 106 CD34+/kg was obtained from patients receiving Rd induction. After first mobilization, inadequate yield was observed in 21% of patients, whereas only 9% of patients failed to collect the target yield after the second mobilization attempt. In conclusion, we confirm that a short induction with lenalidomide allowed sufficient stem cells collection to perform autologous transplantation in 91% of newly diagnosed patients.

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References

  1. Pasquini M . Part I—CIBMTR Summary Slides, 2005. CIBMTR Newsletter 2006; 12: 5–8. http://www.cibmtr.org/ReferenceCenter/Newsletters/PDF/Newsletter_May2006.pdf. (accessed July 30 2010).

    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 Français du Myélome. 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, Katsahian S, Divine M, Leblond V, Dreyfus F, Macro M et al. High-dose therapy and autologous blood stem-cell transplantation compared with conventional treatment in myeloma patients aged 55–65 years: long-term results of a randomized control trial from the Group Myelome-Autogreffe. J Clin Oncol 2005; 23: 9227–9233.

    Article  CAS  PubMed  Google Scholar 

  5. Goldschmidt H, Hegenbart U, Haas R, Hunstein W . Mobilization of peripheral blood progenitor cells with high-dose cyclophosphamide (4 or 7 g/m2) and granulocyte colony-stimulating factor in patients with multiple myeloma. Bone Marrow Transplant 1996; 17: 691–697.

    CAS  PubMed  Google Scholar 

  6. Cottler-Fox MH, Lapidot T, Petit I, Kollet O, DiPersio JF, Link D et al. Stem cell mobilization. Hematology Am Soc Hematol Educ Program 2003, 419–437.

    Article  Google Scholar 

  7. Bolwell B, Goormastic M, Andresen S . Durability of remission after ABMT for NHL: the importance of the 2-year evaluation point. Bone Marrow Transplant 1997; 19: 443–448.

    Article  CAS  PubMed  Google Scholar 

  8. Ketterer N, Salles G, Moullet I, Dumontet C, ElJaafari-Corbin A, Tremisi P et al. Factors associated with successful mobilization of peripheral blood progenitor cells in 200 patients with lymphoid malignancies. Br J Haematol 1998; 103: 235–242.

    Article  CAS  PubMed  Google Scholar 

  9. Russell NH, McQuaker G, Stainer C, Byrne JL, Haynes AP . Stem cell mobilisation in lymphoproliferative diseases. Bone Marrow Transplant 1998; 22: 935–940.

    Article  CAS  PubMed  Google Scholar 

  10. Boccadoro M, Palumbo A, Bringhen S, Merletti F, Ciccone G, Richiardi L et al. Oral melphalan at diagnosis hampers adequate collection of peripheral blood progenitor cells in multiple myeloma. Haematologica 2002; 87: 846–850.

    CAS  PubMed  Google Scholar 

  11. Morris CL, Siegel E, Barlogie B, Cottler-Fox M, Lin P, Fassas A et al. Mobilization of CD34+ cells in elderly patients (>/=70 years) with multiple myeloma: influence of age, prior therapy, platelet count and mobilization regimen. Br J Haematol 2003; 120: 413–423.

    Article  PubMed  Google Scholar 

  12. Perea G, Sureda A, Martino R, Altés A, Martínez C, Cabezudo E et al. Predictive factors for a successful mobilization of peripheral blood CD34+ cells in multiple myeloma. Ann Hematol 2001; 80: 592–597.

    Article  CAS  PubMed  Google Scholar 

  13. Rajkumar SV, Hayman S, Gertz MA, Dispenzieri A, Lacy MQ, Greipp PR et al. Combination therapy with thalidomide plus dexamethasone for newly diagnosed myeloma. J Clin Oncol 2002; 20: 4319–4323.

    Article  CAS  PubMed  Google Scholar 

  14. 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 

  15. 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 

  16. Weber D, Rankin K, Gavino M, Delasalle K, Alexanian R . Thalidomide alone or with dexamethasone for previously untreated multiple myeloma. J Clin Oncol 2003; 21: 16–19.

    Article  CAS  PubMed  Google Scholar 

  17. Rajkumar SV, Richardson PG, Hideshima T, Anderson KC . Proteasome inhibition as a novel therapeutic target in human cancer. J Clin Oncol 2005; 23: 630–639.

    Article  CAS  PubMed  Google Scholar 

  18. 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 

  19. Harousseau JL, Attal M, Leleu X, Troncy J, Pegourie B, Stoppa AM et al. Bortezomib plus dexamethasone as induction treatment prior to autologous stem cell transplantation in patients with newly diagnosed multiple myeloma: results of an IFM phase II study. Haematologica 2006; 91: 1498–1505.

    CAS  PubMed  Google Scholar 

  20. Kumar S, Dispenzieri A, Lacy MQ, Hayman SR, Buadi FK, Gastineau DA et al. Impact of lenalidomide therapy on stem cell mobilization and engraftment post-peripheral blood stem cell transplantation in patients with newly diagnosed myeloma. Leukemia 2007; 21: 2035–2042.

    Article  CAS  PubMed  Google Scholar 

  21. Popat U, Saliba R, Thandi R, Hosing C, Qazilbash M, Anderlini P et al. Impairment of filgrastim-induced stem cell mobilization after prior lenalidomide in patients with multiple myeloma. Biol Blood Marrow Transplant 2009; 15: 718–723.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Mazumder A, Kaufman J, Niesvizky R, Lonial S, Vesole D, Jagannath S . Effect of lenalidomide therapy on mobilization of peripheral blood stem cells in previously untreated multiple myeloma patients. Leukemia 2008; 22: 1280–1281.

    Article  CAS  PubMed  Google Scholar 

  23. 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 

  24. Breitkreutz I, Lokhorst HM, Raab MS, Holt B, Cremer FW, Herrmann D et al. Thalidomide in newly diagnosed multiple myeloma: influence of thalidomide treatment on peripheral blood stem cell collection yield. Leukemia 2007; 21: 1294–1299.

    Article  CAS  PubMed  Google Scholar 

  25. Moreau P, Hulin C, Marit G, Caillot D, Facon T, Lenain P et al. Stem cell collection in patients with de novo multiple myeloma treated with the combination of bortezomib and dexamethasone before autologous stem cell transplantation according to IFM 2005–01 trial. Leukemia 2010; 24: 1233–1235.

    Article  CAS  PubMed  Google Scholar 

  26. Mark T, Stern J, Furst JR, Jayabalan D, Zafar F, LaRow A et al. Stem cell mobilization with cyclophosphamide overcomes the suppressive effect of lenalidomide therapy on stem cell collection in multiple myeloma. Biol Blood Marrow Transplant 2008; 14: 795–798.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Paripati H, Stewart AK, Cabou S, Dueck A, Zepeda VJ, Pirooz N et al. Compromised stem cell mobilization following induction therapy with lenalidomide in myeloma. Leukemia 2008; 22: 1282–1284.

    Article  CAS  PubMed  Google Scholar 

  28. 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 

  29. Goldschmidt H, Lokhorst HM, Bertsch U, van der Holt B, el Jarari L, Salwender H-J et al. Successful harvesting of peripheral hematopoietic stem cells after induction treatment with bortezomib, adriamycin, dexamethasone (PAD) in patients with newly diagnosed multiple myeloma (MM). Blood 2008; 112: (abstract 3470).

  30. Greipp PR, San Miguel J, Durie BG, Crowley JJ, Barlogie B, Bladé J et al. International staging system for multiple myeloma. J Clin Oncol 2005; 23: 3412–3420.

    Article  PubMed  Google Scholar 

  31. http://ctep.cancer.gov: NCI Common terminology criteria for adverse events, (version 3.0).

  32. Hilbe JM . Logistic Regression Models. Chapman & Hall/CRC Press, 2009.

    Book  Google Scholar 

  33. Kumar S, Giralt S, Stadtmauer EA, Harousseau JL, Palumbo A, Bensinger W et al. Mobilization in myeloma revisited: IMWG consensus perspectives on stem cell collection following initial therapy with thalidomide-, lenalidomide-, or bortezomib-containing regimens. Blood 2009; 114: 1729–1735.

    Article  CAS  PubMed  Google Scholar 

  34. Cook RJ, Vogl D, Mangan PA, Cunningham K, Luger S, Porter DL et al. Lenalidomide and stem cell collection in patients with multiple myeloma. J Clin Oncol 2008; 26: (abstract 8547).

    Article  Google Scholar 

  35. Tricot G, Cottler-Fox MH, Calandra G . Safety and efficacy assessment of plerixafor in patients with multiple myeloma proven or predicted to be poor mobilizers, including assessment of tumor cell mobilization. Bone Marrow Transplant 2010; 45: 63–68.

    Article  CAS  PubMed  Google Scholar 

  36. Flomenberg N, Devine SM, Dipersio JF, Liesveld JL, McCarty JM, Rowley SD et al. The use of AMD3100 plus G-CSF for autologous hematopoietic progenitor cell mobilization is superior to G-CSF alone. Blood 2005; 106: 1867–1874.

    Article  CAS  PubMed  Google Scholar 

  37. Koh KR, Janz M, Mapara MY, Lemke B, Stirling D, Dörken B et al. Immunomodulatory derivative of thalidomide (IMiD CC-4047) induces a shift in lineage commitment by suppressing erythropoiesis and promoting myelopoiesis. Blood 2005; 105: 3833–3840.

    Article  CAS  PubMed  Google Scholar 

  38. Anderson G, Gries M, Kurihara N, Honjo T, Anderson J, Donnenberg V et al. Thalidomide derivative CC-4047 inhibits osteoclast formation by down-regulation of PU.1. Blood 2006; 107: 3098–3105.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank the patients who agreed to participate in this study, the nurses, in particular Tiziana Zezza e Silvia Boscolo, and data managers Maria Josè Fornaro, Antonella Fiorillo, Federica Leotta and Debora Caldarazzo. The study RV MM PI 209 was funded by the Fondazione Neoplasie Sangue Onlus. Celgene supplied free Lenalidomide for the study RV MM PI 209. Celgene had no role in the study design, data analysis, data interpretation or writing of the report. We would like to acknowledge the editorial assistance of Anna Georgieva, MD, PhD, and Adriana Stan, PhD, with Excerpta Medica during the development of this publication.

Author contributions

Professor Boccadoro and Dr Palumbo designed the research RV MM PI 209; Dr Cavallo and Dr Lupo collected, analyzed and interpreted the data; Dr Cavallo and Dr Passera performed statistical analysis; Dr Cavallo, Professor Boccadoro and Dr Palumbo wrote the manuscript. All the other authors enrolled patients, and all authors reviewed and approved the manuscript.

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Authors and Affiliations

  1. Division of Hematology, Myeloma Unit, University of Torino, AOU S Giovanni Battista, Torino, Italy

    F Cavallo, S Bringhen, B Lupo, P Omedè, M Boccadoro & A Palumbo

  2. Division of Hematology, Ferrarotto Hospital, Catania, Italy

    G Milone

  3. Hadassah Medical Centre, Jerusalem, Israel

    D Ben-Yehuda

  4. Hematology Division and Cord Blood Bank, Chaim Sheba Medical Center, Tel Hashomer, Israel

    A Nagler

  5. Department of Hematology, Sapienza University of Rome, Rome, Italy

    E Calabrese & M T Petrucci

  6. Department of Stem Cell Transplant, Unit of Hematology, Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo, Italy

    N Cascavilla

  7. UO of Hematology and Allogeneic Bone Marrow Transplantation, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milano, Italy

    V Montefusco

  8. Institute of Onco-Hematology, University of Perugia, Santa Maria Hospital, Terni, Italy

    A M Liberati

  9. Division of Hematology, Spedali Civili Hospital, Brescia, Italy

    C Crippa

  10. Division of Hematology and TMO S Gerardo Hospital, Monza, Italy

    F Rossini

  11. Radiochemistry Unit c/o SC Medicina Nucleare 2, Azienda Ospedaliero-Universitaria San Giovanni Battista, Torino, Italy

    R Passera

  12. Clinic of Hematology, Transplant Center and Cell Therapy ‘Carlo Melzi’, AOU ‘S Maria della Misericordia’, Udine, Italy

    F Patriarca

  13. Haematology Departement, Niguarda Hospital, Milan, Italy

    A M Cafro

  14. Hematology 1, AOU S. Martino, Hematology 1, Genova, Italy

    A M Carella

  15. Department of Onco-Hematology, Istituto Scientifico Universitario San Raffaele, Milano, Italy

    J Peccatori

  16. Division of Hematology, University of Federico II, Napoli, Italy

    L Catalano

  17. Division of Hematology, S Eugenio Hospital, Rome, Italy

    T Caravita

  18. Department of Onco-Hematology, IRCCS, Centro di Riferimento Oncologico della Basilicata, Rionero in Vulture (Pz), Italy

    P Musto

Authors
  1. F Cavallo
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  2. S Bringhen
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  3. G Milone
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  6. E Calabrese
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  8. V Montefusco
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  9. B Lupo
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  10. A M Liberati
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  11. C Crippa
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  12. F Rossini
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  13. R Passera
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  14. F Patriarca
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  15. A M Cafro
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  16. P Omedè
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  17. A M Carella
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  18. J Peccatori
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  19. L Catalano
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  20. T Caravita
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  21. P Musto
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  22. M T Petrucci
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  23. M Boccadoro
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  24. A Palumbo
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Corresponding author

Correspondence to A Palumbo.

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Competing interests

Dr Cavallo has received honoraria from Celgene and Janssen-Cilag; Dr Bringhen has received honoraria from Celgene, Janssen-Cilag, Novartis and Merck; Dr Patriarca has received research funds and honoraria from Celgene and Janssen-Cilag; Dr Musto has received research founds and honoraria from Celgene; Dr Petrucci has received honoraria from Celgene and Janssen-Cilag; Professor Boccadoro has received research support, consultancy and scientific advisory board from Celgene and Janssen Cilag; Dr Palumbo has received honoraria from Celgene, Janssen-Cilag, Merck, Amgen and Advisory Committee from Celgene, Janssen-Cilag. All other authors declare no conflict of interest.

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Cavallo, F., Bringhen, S., Milone, G. et al. Stem cell mobilization in patients with newly diagnosed multiple myeloma after lenalidomide induction therapy. Leukemia 25, 1627–1631 (2011). https://doi.org/10.1038/leu.2011.131

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  • DOI: https://doi.org/10.1038/leu.2011.131

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