Plerixafor

Číslo: 3 / 2011 (Obsah)
Rubrika: Profily léčiv
Obor: Hematoonkologie
Autoři: MUDr. Zdeněk Kořístek, Ph.D.
Autoři - působiště: Interní hematoonkologická klinika, FN Brno
Klíčová slova: plerixafor, CXCR4, SDF-1α, mobilizace, krvetvorné buňky, transplantace buněk krvetvorby
Citace: 1 De Clercq E, Yamamoto N, Pauwels R, et al. Highly potent and selective inhibition of human immunodeficiency virus by the bicyclam derivate JM3100. Antimicrob Agents Chemother 1994;38:668–74. 2 Schols D, Esté JA, Henson G, et al. Bicyclams, a class of potent anti-HIV agents, are targeted at the HIV coreceptor fusin/CXCR-4. Antiviral Res 1997;35:147–156. 3 Liles WC, Broxmeyer HE, Rodger E, et al. Mobilization of hematopoietic progenitor cells in healthy volunteers by AMD3100, a CXCR4 antagonist. Blood 2003;102:2728–30. 4 Devine SM, Flomenberg N, Vesole DH, et al. Rapid mobilization of CD34+ cells following administration of the CXCR4 antagonist AMD3100 to patients with multiple myeloma and non-Hodgkin's lymphoma. J Clin Oncol 2004;22:1095–102. 5 Liles WC, Rodger E, Broxmeyer HE, et al. Augmented mobilization and collection of CD34+ hematopoietic cells from normal human volunteers stimulated with granulocyte-colony-stimulating factor by single-dose administration of AMD3100, a CXCR4 antagonist. Transfusion 2005;45:295–300 6 Flomenberg N, Devine SM, di Persio JF, et al. The use of AMD3100 plus G-CSF for autologous hematopoietic progenitor cell mobilization is superior to G-CSF alone. Blood 2005;106:1867–74. 7 Micallef IN, Stiff PJ, DiPersio J, et al. Successful stem cell remobilization using plerixafor (Mozobil) plus granulocyte colony-stimulating factor in patients with non-Hodgkin lymphoma: results from the plerixafor NHL phase 3 study rescue protocol. Biol Blood Marrow Transplant 2009;15:1578–86. 8 Weaver CH, Tauer K, Zhen B, et al. Second attempts at mobilization of peripheral blood stem cells in patients with initial low CD341 cell yields. J Hematother 1998;7:241–9. 9 Boeve S, Strupeck J, Creech S, et al. Analysis of remobilization success in patients undergoing autologous stem cell transplants who fail an initial mobilization: risk factors, cytokine use and cost. Bone Marrow Transplant 2004;33:997–1003. 10 Dugan MJ, Maziarz RT, Bensinger WI, et al. Safety and preliminary efficacy of plerixafor (Mozobil) in combination with chemotherapy and G-CSF: an open-label, multicenter, exploratory trial in patients with multiple myeloma and non-Hodgkin’s lymphoma undergoing stem cell mobilization. Bone Marrow Transplant 2010;45:39–47. 11 DiPersio JF, Micallef IN, Stiff PJ, et al. Phase III prospective randomized double-blind placebo-controlled trial of plerixafor plus granulocyte colony-stimulating factor compared with placebo plus granulocyte colony-stimulating factor for auto-logous stem-cell mobilisation and transplantation for patients with non-Hodgkin’s lymphoma. J Clin Oncol 2009;27:4767–73. 12 DiPersio JF, Stadtmauer EA, Nademanee A, et al. Plerixafor and G-CSF versus placebo and G-CSF to mobilize hematopoietic stem cells for autologous stem cell transplantation in patients with multiple myeloma. Blood 2009;113:5720–6. 13 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; 45:63–8. 14 Mozobil® (plerixafor). EU summary of product characteristics. Naarden, The Netherlands: Genzyme Europe BV;2009. 15 Kořístek Z, Štěrba J, Kepák T et al. European paediatric experience with plerixafor for autologous PBSC mobilization from children failing to mobilize PBSC by conventional means: an initial series of 6 patients from 2 centres. Bone Marrow Transplant 2011;46(Suppl 1):S342. 16 Reuss-Borst MA, Klein G, Waller HD, et al. Differential expression of adhesion molecules in acute leukemia. Leukemia 1995; 9:869–74. 17 Nervi B, Ramirez P, Rettig MP, et al. Chemosensitization of acute myeloid leukemia (AML) following mobilization by the CXCR4 antagonist AMD3100. Blood 2009;113:6206–14. 18 Zeng Z, Shi YX, Samudio IJ, et al. Targeting the leukemia microenvironment by CXCR4 inhibition overcomes resistance to kinase inhibitors and chemotherapy in AML. Blood 2009; 113:6215–24. 19 Konoplev S, Rassidakis GZ, Estey E, et al. Overexpression of CXCR4 predicts adverse overall and event-free survival in patients with unmutated FLT3 acute myeloid leukemia with normal karyotype. Cancer 2007;109:1152–6. 20 Uy GL, Rettig MP, McFarland K, et al. A phase I/II study of chemosensitization with the CXCR4 antagonist plerixafor in relapsed or refractory AML. Blood 2009;114(Suppl):Abstract 787. 21 Luker KE, Luker GD. Functions of CXCL12 and CXCR4 in breast cancer. Cancer Lett 2006, 238:30–41. 22 Andreeff M. Future applications of CXCR4 inhibition. Lesson in: CXCR4 blockade: practical consideration for mobilization and transplant. Educational event at Annual Meeting of The European Group for Blood and Marrow Transplantation, 2011. 23 Stiff P, Micallef I, McCarthy P, et al. Treatment with plerixafor in non-Hodgkin's lymphoma and multiple myeloma patients to increase the number of peripheral blood stem cells when given a mobilizing regimen of G-CSF: implications for the heavily pretreated patient. Biol Blood Marrow Transplant 2009;15:249–56. 24 Tarantolo SR, McSweeney PA, Micallef IN, et al. Plerixafor can predictably mobilize hematopoietic stem cells in patients with multiple myeloma previously treated with lenalidomide. Biol Blood Marrow Transplant 2009;15 (Suppl):37. 25 Calandra G, McCarty J, McGuirk J, et al. AMD3100 plus G-CSF can successfully mobilize CD34+ cells from non-Hodgkin's lymphoma, Hodgkin's disease and multiple myeloma patients previously failing mobilization with chemotherapy and/or cytokine treatment: compassionate use data. Bone Marrow Transplant 2008;41:331–8. 26 Delgado E, LeMaistreCF, Bachier C, et al. Cost analysis of mobilization and autologous transplantation in patients who received AMD 3100 after failing standard mobilization. Blood 2008;112(Suppl):2151a. 27 Duarte RF, Marín P, Ortiz M, et al. Plerixafor plus G-CSF can successfully mobilise CD34+ cells from patients with lymphoid malignancies who have previously failed chemotherapy and/or cytokine mobilisation: compassionate use experience in Spain. Bone Marrow Transplant 2009;43(Suppl 1):S80. 28 Fowler CJ, Dunn A, Hayes-Lattin B, et al. Rescue from failed growth factor and/or chemotherapy HSC mobilization with G-CSF and plerixafor (AMD3100): an institutional experience. Bone Marrow Transplant 2009;43:909–17. 29 Gordon WC, Johnson PRE, Roddie PH, et al. Plerixafor is highly effective in the mobilization of PBSC for autologous transplantation from patients failing to mobilise by conventional means: the initial Scottish experience in three transplant centres. Bone Marrow Transplant 2009;43(Suppl 1):S113. 30 Micallef IN, Maurer M, Ansell SM, et al. Peripheral blood CD34 count can predict successful progenitor cell mobilization in poor mobiliziers treated with plerixafor and G-CSF. Biol Blood Marrow Transplant 2009;15(Suppl):70. 31 Shaughnessy P, McSweeney P, Solomon S, et al. Effect of plerixafor plus G-CSF among patients who failed to collect sufficient haematopoietic stem cells after mobilisation attempt with chemotherapy plus cytokines. Bone Marrow Transplant 2009;43(Suppl 1):S80. 32 Gerlach LO, Skerlj RT, Bridger GJ, et al. Molecular interactions of cyclam and bicyclam non-peptide antagonists with the CXCR4 chemokine receptor. J Biol Chem 2001;276:14153–60.

Souhrn

Plerixafor je selektivní reverzibilní antagonista receptoru CXCR4 a jeho účinek spočívá v narušení interakce CXCR4/SDF-1α (stromal cell-derived factor-1α), která patří mezi hlavní mechanismy udržující krvetvorné buňky (HSC – hema-topoietic stem cells) v kostní dřeni. Inhibice vazby SDF-1α/CXCR4 vede během několika hodin k poměrně mohutnému vyplavování HSC do periferní krve neboli k jejich mobilizaci. HSC mohou být následně z krve získávány pomocí aferézy a použity pro transplantaci buněk krvetvorby. Ještě většího mobilizačního účinku čili vyšší koncentrace HSC v krvi je dosaženo v případě, že je před podáním plerixaforu krvetvorba stimulována pomocí G-CSF (granulocyte-colony stimulating factor) po 4–5 dní. Plerixafor vykazuje vysokou účinnost také u pacientů, u kterých obvyklým postupem (G-CSF nebo chemoterapie + G-CSF) nedosáhneme dostatečné mobilizace a aferéza není provedena nebo je málo výtěžná. Remobilizace s použitím plerixaforu v kombinaci s G-CSF je úspěšná u přibližně 80 % těchto pacientů, které označujeme pojmem „poor mobilizers."

Literatura

1
De Clercq E, Yamamoto N, Pauwels R, et al. Highly potent and selective inhibition of human immunodeficiency virus by the bicyclam derivate JM3100. Antimicrob Agents Chemother 1994;38:668–74. 2 Schols D, Esté JA, Henson G, et al. Bicyclams, a class of potent anti-HIV agents, are targeted at the HIV coreceptor fusin/CXCR-4. Antiviral Res 1997;35:147–156. 3 Liles WC, Broxmeyer HE, Rodger E, et al. Mobilization of hematopoietic progenitor cells in healthy volunteers by AMD3100, a CXCR4 antagonist. Blood 2003;102:2728–30. 4 Devine SM, Flomenberg N, Vesole DH, et al. Rapid mobilization of CD34+ cells following administration of the CXCR4 antagonist AMD3100 to patients with multiple myeloma and non-Hodgkin's lymphoma. J Clin Oncol 2004;22:1095–102. 5 Liles WC, Rodger E, Broxmeyer HE, et al. Augmented mobilization and collection of CD34+ hematopoietic cells from normal human volunteers stimulated with granulocyte-colony-stimulating factor by single-dose administration of AMD3100, a CXCR4 antagonist. Transfusion 2005;45:295–300 6 Flomenberg N, Devine SM, di Persio JF, et al. The use of AMD3100 plus G-CSF for autologous hematopoietic progenitor cell mobilization is superior to G-CSF alone. Blood 2005;106:1867–74. 7 Micallef IN, Stiff PJ, DiPersio J, et al. Successful stem cell remobilization using plerixafor (Mozobil) plus granulocyte colony-stimulating factor in patients with non-Hodgkin lymphoma: results from the plerixafor NHL phase 3 study rescue protocol. Biol Blood Marrow Transplant 2009;15:1578–86. 8 Weaver CH, Tauer K, Zhen B, et al. Second attempts at mobilization of peripheral blood stem cells in patients with initial low CD341 cell yields. J Hematother 1998;7:241–9. 9 Boeve S, Strupeck J, Creech S, et al. Analysis of remobilization success in patients undergoing autologous stem cell transplants who fail an initial mobilization: risk factors, cytokine use and cost. Bone Marrow Transplant 2004;33:997–1003.
10
Dugan MJ, Maziarz RT, Bensinger WI, et al. Safety and preliminary efficacy of plerixafor (Mozobil) in combination with chemotherapy and G-CSF: an open-label, multicenter, exploratory trial in patients with multiple myeloma and non-Hodgkin’s lymphoma undergoing stem cell mobilization. Bone Marrow Transplant 2010;45:39–47.
11
DiPersio JF, Micallef IN, Stiff PJ, et al. Phase III prospective randomized double-blind placebo-controlled trial of plerixafor plus granulocyte colony-stimulating factor compared with placebo plus granulocyte colony-stimulating factor for auto-logous stem-cell mobilisation and transplantation for patients with non-Hodgkin’s lymphoma. J Clin Oncol 2009;27:4767–73.
12
DiPersio JF, Stadtmauer EA, Nademanee A, et al. Plerixafor and G-CSF versus placebo and G-CSF to mobilize hematopoietic stem cells for autologous stem cell transplantation in patients with multiple myeloma. Blood 2009;113:5720–6.
13
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; 45:63–8.
14
Mozobil® (plerixafor). EU summary of product characteristics. Naarden, The Netherlands: Genzyme Europe BV;2009.
15
Kořístek Z, Štěrba J, Kepák T et al. European paediatric experience with plerixafor for autologous PBSC mobilization from children failing to mobilize PBSC by conventional means: an initial series of 6 patients from 2 centres. Bone Marrow Transplant 2011;46(Suppl 1):S342.
16
Reuss-Borst MA, Klein G, Waller HD, et al. Differential expression of adhesion molecules in acute leukemia. Leukemia 1995; 9:869–74.
17
Nervi B, Ramirez P, Rettig MP, et al. Chemosensitization of acute myeloid leukemia (AML) following mobilization by the CXCR4 antagonist AMD3100. Blood 2009;113:6206–14.
18
Zeng Z, Shi YX, Samudio IJ, et al. Targeting the leukemia microenvironment by CXCR4 inhibition overcomes resistance to kinase inhibitors and chemotherapy in AML. Blood 2009; 113:6215–24.
19
Konoplev S, Rassidakis GZ, Estey E, et al. Overexpression of CXCR4 predicts adverse overall and event-free survival in patients with unmutated FLT3 acute myeloid leukemia with normal karyotype. Cancer 2007;109:1152–6.
20
Uy GL, Rettig MP, McFarland K, et al. A phase I/II study of chemosensitization with the CXCR4 antagonist plerixafor in relapsed or refractory AML. Blood 2009;114(Suppl):Abstract 787.
21
Luker KE, Luker GD. Functions of CXCL12 and CXCR4 in breast cancer. Cancer Lett 2006, 238:30–41.
22
Andreeff M. Future applications of CXCR4 inhibition. Lesson in: CXCR4 blockade: practical consideration for mobilization and transplant. Educational event at Annual Meeting of The European Group for Blood and Marrow Transplantation, 2011.
23
Stiff P, Micallef I, McCarthy P, et al. Treatment with plerixafor in non-Hodgkin's lymphoma and multiple myeloma patients to increase the number of peripheral blood stem cells when given a mobilizing regimen of G-CSF: implications for the heavily pretreated patient. Biol Blood Marrow Transplant 2009;15:249–56.
24
Tarantolo SR, McSweeney PA, Micallef IN, et al. Plerixafor can predictably mobilize hematopoietic stem cells in patients with multiple myeloma previously treated with lenalidomide. Biol Blood Marrow Transplant 2009;15 (Suppl):37.
25
Calandra G, McCarty J, McGuirk J, et al. AMD3100 plus G-CSF can successfully mobilize CD34+ cells from non-Hodgkin's lymphoma, Hodgkin's disease and multiple myeloma patients previously failing mobilization with chemotherapy and/or cytokine treatment: compassionate use data. Bone Marrow Transplant 2008;41:331–8.
26
Delgado E, LeMaistreCF, Bachier C, et al. Cost analysis of mobilization and autologous transplantation in patients who received AMD 3100 after failing standard mobilization. Blood 2008;112(Suppl):2151a.
27
Duarte RF, Marín P, Ortiz M, et al. Plerixafor plus G-CSF can successfully mobilise CD34+ cells from patients with lymphoid malignancies who have previously failed chemotherapy and/or cytokine mobilisation: compassionate use experience in Spain. Bone Marrow Transplant 2009;43(Suppl 1):S80.
28
Fowler CJ, Dunn A, Hayes-Lattin B, et al. Rescue from failed growth factor and/or chemotherapy HSC mobilization with G-CSF and plerixafor (AMD3100): an institutional experience. Bone Marrow Transplant 2009;43:909–17.
29
Gordon WC, Johnson PRE, Roddie PH, et al. Plerixafor is highly effective in the mobilization of PBSC for autologous transplantation from patients failing to mobilise by conventional means: the initial Scottish experience in three transplant centres. Bone Marrow Transplant 2009;43(Suppl 1):S113.
30
Micallef IN, Maurer M, Ansell SM, et al. Peripheral blood CD34 count can predict successful progenitor cell mobilization in poor mobiliziers treated with plerixafor and G-CSF. Biol Blood Marrow Transplant 2009;15(Suppl):70.
31
Shaughnessy P, McSweeney P, Solomon S, et al. Effect of plerixafor plus G-CSF among patients who failed to collect sufficient haematopoietic stem cells after mobilisation attempt with chemotherapy plus cytokines. Bone Marrow Transplant 2009;43(Suppl 1):S80.
32
Gerlach LO, Skerlj RT, Bridger GJ, et al. Molecular interactions of cyclam and bicyclam non-peptide antagonists with the CXCR4 chemokine receptor. J Biol Chem 2001;276:14153–60.

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