Results from a multicenter, noninterventional registry study for multiple myeloma patients who received stem cell mobilization regimens with and without plerixafor

Curly Morris, Christian Chabannon, Tamas Masszi, Nigel Russell, Hareth Nahi, Guido Kobbe, Marta Krejci, Holger W Auner, David Pohlreich, Patrick Hayden, Grzegorz W Basak, Stig Lenhoff, Nicolaas Schaap, Anja van Biezen, Cora Knol, Simona Iacobelli, Qianying Liu, Marina Celanovic, Laurent Garderet, Nicolaus Kröger, Curly Morris, Christian Chabannon, Tamas Masszi, Nigel Russell, Hareth Nahi, Guido Kobbe, Marta Krejci, Holger W Auner, David Pohlreich, Patrick Hayden, Grzegorz W Basak, Stig Lenhoff, Nicolaas Schaap, Anja van Biezen, Cora Knol, Simona Iacobelli, Qianying Liu, Marina Celanovic, Laurent Garderet, Nicolaus Kröger

Abstract

Plerixafor plus granulocyte-colony stimulating factor (G-CSF) enhances the mobilization of hematopoietic stem cells (HSCs) for collection and subsequent autologous hematopoietic stem cell transplantation (HSCT) in patients with multiple myeloma (MM). This international, multicenter, noninterventional registry study (NCT01362972), evaluated long-term outcomes for MM patients who received plerixafor versus other mobilization regimens. The comparisons were: G-CSF + plerixafor (G-CSF + P) versus G-CSF-; G-CSF + P versus G-CSF + chemotherapy (G-CSF + C); and G-CSF + P + C versus G-CSF + C. Propensity score matching was used to balance groups. Primary outcome measures were progression free survival (PFS), overall survival (OS), and cumulative incidence of relapse (CIR) after transplantation. After propensity matching, 77 versus 41 patients in the G-CSF + P versus G-CSF cohorts, 129 versus 129 in the G-CSF + P versus G-CSF + C cohorts, and 117 versus 117 in the G-CSF + P + C versus G-CSF + C cohorts were matched, respectively. Propensity score matching resulted in a smaller sample size and imbalances were not completely overcome. For both PFS and OS, the upper limits of the hazard ratio 95% confidence intervals exceeded prespecified boundaries; noninferiority was not demonstrated. CIR rates were higher in the plerixafor cohorts. G-CSF + P remains an option for the mobilization of HSCs in poor mobilizers with MM with no substantial differences in PFS, OS, and CIR in comparison with other regimens.

Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Patient eligibility and treatment
Fig. 2
Fig. 2
Progression (event) free survival for each of the comparison groups, G-CSF plus plerixafor versus G-CSF alone (comparison 1); G-CSF plus plerixafor versus G-CSF plus chemotherapy (comparison 2); G-CSF plus plerixafor plus chemotherapy versus G-CSF plus chemotherapy (comparison 3)
Fig. 3
Fig. 3
Overall (event-free) survival for each of the comparison groups, G-CSF plus plerixafor versus G-CSF alone (comparison 1); G-CSF plus plerixafor versus G-CSF plus chemotherapy (comparison 2); G-CSF plus plerixafor plus chemotherapy versus G-CSF plus chemotherapy (comparison 3)
Fig. 4
Fig. 4
Cumulative incidence of relapse with death without progression/relapse as a competing risk for each of the comparison groups, G-CSF plus plerixafor versus G-CSF alone (comparison 1); G-CSF plus plerixafor versus G-CSF plus chemotherapy (comparison 2); G-CSF plus plerixafor plus chemotherapy versus G-CSF plus chemotherapy (comparison 3)

References

    1. DiPersio JF, Uy GL, Yasothan U, Kirkpatrick P. Plerixafor. Nat Rev Drug Discov. 2009;8:105–6. doi: 10.1038/nrd2819.
    1. Nervi B, Link DC, DiPersio JF. Cytokines and hematopoietic stem cell mobilization. J Cell Biochem. 2006;99:690–705. doi: 10.1002/jcb.21043.
    1. Fruehauf S, Seeger T. New strategies for mobilization of hematopoietic stem cells. Future Oncol. 2005;1:375–83. doi: 10.1517/14796694.1.3.375.
    1. Lapidot T, Dar A, Kollet O. How do stem cells find their way home? Blood. 2005;106:1901–10. doi: 10.1182/blood-2005-04-1417.
    1. Pirracchio R, Resche-Rigon M, Chevret S. Evaluation of the propensity score methods for estimating marginal odds ratios in case of small sample size. BMC Med Res Methodol. 2012;12:70. doi: 10.1186/1471-2288-12-70.
    1. Kaplan EL, Meier P. Nonparametric estimation from incomplete observation. J Am Stat Assoc. 1958;53:457–81. doi: 10.1080/01621459.1958.10501452.
    1. Brioli A, Perrone G, Patriarca F, Pezzi A, Nobile F, Ballerini F, et al. Successful mobilization of PBSCs predicts favorable outcomes in multiple myeloma patients treated with novel agents and autologous transplantation. Bone Marrow Transpl. 2015;50:673–8. doi: 10.1038/bmt.2014.322.
    1. Shah N, Callander N, Ganguly S, Gul Z, Hamadani M, Costa L, et al. Hematopoietic stem cell transplantation for multiple myeloma: guidelines from the American Society for Blood and Marrow Transplantation. Biol Blood Marrow Transpl. 2015;21:1155–66. doi: 10.1016/j.bbmt.2015.03.002.
    1. Lee KH, Jung SK, Kim SJ, Jang JH, Kim K, Kim WS, et al. Incidence and risk factors of poor mobilization in adult autologous peripheral blood stem cell transplantation: a single-centre experience. Vox Sang. 2014;107:407–15. doi: 10.1111/vox.12183.
    1. Sancho JM, Morgades M, Grifols JR, Junca J, Guardia R, Vives S, et al. Predictive factors for poor peripheral blood stem cell mobilization and peak CD34(+) cell count to guide pre-emptive or immediate rescue mobilization. Cytotherapy. 2012;14:823–9. doi: 10.3109/14653249.2012.681042.
    1. Wuchter P, Ran D, Bruckner T, Schmitt T, Witzens-Harig M, Neben K, et al. Poor mobilization of hematopoietic stem cells-definitions, incidence, risk factors, and impact on outcome of autologous transplantation. Biol Blood Marrow Transpl. 2010;16:490–9. doi: 10.1016/j.bbmt.2009.11.012.
    1. Cook G, Williams C, Brown JM, Cairns DA, Cavenagh J, Snowden JA, et al. High-dose chemotherapy plus autologous stem-cell transplantation as consolidation therapy in patients with relapsed multiple myeloma after previous autologous stem-cell transplantation (NCRI Myeloma X Relapse [Intensive trial]): a randomised, open-label, phase 3 trial. Lancet Oncol. 2014;15:874–85. doi: 10.1016/S1470-2045(14)70245-1.
    1. Giralt S, Garderet L, Durie B, Cook G, Gahrton G, Bruno B, et al. American Society of Blood and Marrow Transplantation, European Society of Blood and Marrow Transplantation, Blood and Marrow Transplant Clinical Trials Network, and International Myeloma Working Group Consensus Conference on salvage hematopoietic cell transplantation in patients with relapsed multiple myeloma. Biol Blood Marrow Transpl. 2015;21:2039–51. doi: 10.1016/j.bbmt.2015.09.016.
    1. Maybury B, Cook G, Pratt G, Yong K, Ramasamy K. Augmenting autologous stem cell transplantation to improve outcomes in myeloma. Biol Blood Marrow Transpl. 2016;22:1926–37. doi: 10.1016/j.bbmt.2016.06.004.
    1. Pratt G, Morris TC. Review of the NICE guidelines for multiple myeloma. Int J Lab Hematol. 2017;39:3–13. doi: 10.1111/ijlh.12581.
    1. Kim JS, Yoon DH, Park S, Yoon SS, Cho SG, Min CK, et al. Prognostic factors for re-mobilization using plerixafor and granulocyte colony-stimulating factor (G-CSF) in patients with malignant lymphoma or multiple myeloma previously failing mobilization with G-CSF with or without chemotherapy: the Korean multicenter retrospective study. Ann Hematol. 2016;95:603–11. doi: 10.1007/s00277-016-2589-y.
    1. Sheppard D, Bredeson C, Huebsch L, Allan D, Tay J. A plerixafor-based strategy allows adequate hematopoietic stem cell collection in poor mobilizers: results from the Canadian Special Access Program. Bone Marrow Transpl. 2014;49:751–5. doi: 10.1038/bmt.2014.33.
    1. Spoerl S, Peter R, Wascher D, Gotze K, Verbeek M, Peschel C, et al. Patients’ outcome after rescue plerixafor administration for autologous stem cell mobilization: a single-center retrospective analysis. Transfusion. 2017;57:115–21. doi: 10.1111/trf.13883.
    1. Micallef IN, Stiff PJ, Nademanee AP, Maziarz RT, Horwitz ME, Stadtmauer EA, et al. Plerixafor plus granulocyte colony-stimulating factor for patients with non-hodgkin lymphoma and multiple myeloma: long-term follow-up report. Biol Blood Marrow Transpl. 2018;24:1187–95. doi: 10.1016/j.bbmt.2018.01.039.
    1. Nahi H, Celanovic M, Liu Q, Lund J, Peceliunas V. A pilot, exploratory, randomized, phase ii safety study evaluating tumor cell mobilization and apheresis product contamination in patients treated with granulocyte colony-stimulating factor alone or plus plerixafor. Biol Blood Marrow Transpl. 2019;25:34–40. doi: 10.1016/j.bbmt.2018.08.020.
    1. Chang H, Qi XY, Samiee S, Yi QL, Chen C, Trudel S, et al. Genetic risk identifies multiple myeloma patients who do not benefit from autologous stem cell transplantation. Bone Marrow Transpl. 2005;36:793–6. doi: 10.1038/sj.bmt.1705131.
    1. Avet-Loiseau H, Attal M, Moreau P, Charbonnel C, Garban F, Hulin C, et al. Genetic abnormalities and survival in multiple myeloma: the experience of the Intergroupe Francophone du Myelome. Blood. 2007;109:3489–95. doi: 10.1182/blood-2006-08-040410.
    1. Shaughnessy JD, Jr., Zhan F, Burington BE, Huang Y, Colla S, Hanamura I, et al. A validated gene expression model of high-risk multiple myeloma is defined by deregulated expression of genes mapping to chromosome 1. Blood. 2007;109:2276–84. doi: 10.1182/blood-2006-07-038430.
    1. Garrido MM, Kelley AS, Paris J, Roza K, Meier DE, Morrison RS, et al. Methods for constructing and assessing propensity scores. Health Serv Res. 2014;49:1701–20. doi: 10.1111/1475-6773.12182.
    1. Costa LJ, Abbas J, Hogan KR, Kramer C, McDonald K, Butcher CD, et al. Growth factor plus preemptive (‘just-in-time’) plerixafor successfully mobilizes hematopoietic stem cells in multiple myeloma patients despite prior lenalidomide exposure. Bone Marrow Transpl. 2012;47:1403–8. doi: 10.1038/bmt.2012.60.
    1. Wehr VH, Corneau JM. Efficacy and cost analysis of a plerixafor protocol for peripheral blood stem-cell mobilization in patients with multiple myeloma or non-hodgkin lymphoma. J Hematol Oncol Pharm. 2016;6:139–43.
    1. Micallef IN, Sinha S, Gastineau DA, Wolf R, Inwards DJ, Gertz MA, et al. Cost-effectiveness analysis of a risk-adapted algorithm of plerixafor use for autologous peripheral blood stem cell mobilization. Biol Blood Marrow Transpl. 2013;19:87–93. doi: 10.1016/j.bbmt.2012.08.010.
    1. Douglas KW, Gilleece M, Hayden P, Hunter H, Johnson PRE, Kallmeyer C, et al. UK consensus statement on the use of plerixafor to facilitate autologous peripheral blood stem cell collection to support high-dose chemoradiotherapy for patients with malignancy. J Clin Apher. 2018;33:46–59. doi: 10.1002/jca.21563.
    1. Duong HK, Savani BN, Copelan E, Devine S, Costa LJ, Wingard JR, et al. Peripheral blood progenitor cell mobilization for autologous and allogeneic hematopoietic cell transplantation: guidelines from the American Society for Blood and Marrow Transplantation. Biol Blood Marrow Transpl. 2014;20:1262–73. doi: 10.1016/j.bbmt.2014.05.003.
    1. Moreb JS, Byrne M, Shugarman I, Zou F, Xiong S, May WS, et al. Poor peripheral blood stem cell mobilization affects long-term outcomes in multiple myeloma patients undergoing autologous stem cell transplantation. J Clin Apher. 2018;33:29–37. doi: 10.1002/jca.21556.

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