Ofatumumab

Číslo: 5 / 2011 (Obsah)
Rubrika: Profily léčiv
Obor: Hematoonkologie
Autoři: MUDr. Martin Šimkovič
MUDr. Lukáš Smolej, Ph.D.
Autoři - působiště: Oddělení klinické hematologie, II. interní klinika LF UK a FN, Hradec Králové
Klíčová slova: ofatumumab, CD20, chronická lymfocytární leukemie, infuzní toxicita
Citace: 1 Smolej L. Modern concepts in the treatment of chronic lymphocytic leukemia. Hematology 2009;14:249−54. 2 Stashenko P, Nadler LM, Hardy R, et al. Characterization of a human B lymphocyte-specific antigen. J Immunol 1980; 125:1678−85. 3 Hallek M, Fischer K, Fingerle-Rowson G, et al. Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, phase 3 trial. Lancet 2010;376:1164−74. 4 Robak T, Dmoszynska A, Solal-Céligny P, et al. Rituximab plus fludarabine and cyclophosphamide prolongs progression-free survival compared with fludarabine and cyclophosphamide alone in previously treated chronic lymphocytic leukaemia. J Clin Oncol 2010;28:1756−65. 5 Teeling JL, French RR, Cragg MS, et al. Characterization of new human CD20 monoclonal antibodies with potent cytolytic activity against non-Hodgkin lymphomas. Blood 2004;104: 1793−800. 6 Glennie MJ, French RR, Cragg MS, et al. Mechanisms of killing by anti-CD20 monoclonal antibodies. Mol Immunol 2007;44: 3823−37. 7 Golay J, Lazzari M, Facchinetti V, et al. CD20 levels determine the in vitro susceptibility to rituximab and complement of B-cell chronic lymphocytic leukemia: further regulation by CD55 and CD59. Blood 2001;98:3383−9. 8 Teeling JL, Mackus WJ, Wiegman LJ, et al. The biological activity of human CD20 monoclonal antibodies is linked to unique epitopes on CD20. J Immunol 2006;177:362−71. 9 Robak T. Ofatumumab, a human monoclonal antibody for lymphoid malignancies and autoimmune disorders. Curr Opin Mol Ther 2008;10:294−309. 10 Ofatumumab summary of products characteristics. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/ human/001131/WC500093091.pdf 11 Bleeker WK, Munk ME, Mackus WJ, et al. Estimation of dose requirements for sustained in vivo activity of a therapeutic human anti-CD20 antibody. Br J Haematol 2008;140:303−12. 12 Coiffier B, Lepretre S, Pedersen LM, et al. Safety and efficacy of ofatumumab, a fully human monoclonal anti-CD20 antibody, in patients with relapsed or refractory B-cell chronic lymphocytic leukemia: a phase 1−2 study. Blood 2008;111: 1094−100. 13 Wierda WG, Kipps TJ, Mayer J, et al. Ofatumumab as single-agent CD20 immunotherapy in fludarabine-refractory chronic lymphocytic leukemia. J Clin Oncol 2010;28:1749−55. 14 Wierda WG, Kipps TJ, Durig J, et al. Chemoimmunotherapy with O-FC in previously untreated patients with chronic lymphocytic leukemia. Blood 2011;117:6450−8. 15 Hallek M, Fischer K, Fingerle-Rowson G, et al. Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, phase 3 trial. Lancet 201;376(9747):1164−74. 16 Faderl S, Wierda W, O’Brien S, et al. Fludarabine, cyclo-phosphamide, mitoxantrone plus rituximab (FCM-R) in frontline CLL < 70 Years. Leukemia Research 2010;34:284−8. 17 http://www.clinicaltrials.gov./ct2/results?term=ofatumumab +AND+CLL. 18 Østergaard M, Baslund B, Rigby W, et al. Ofatumumab, a human anti-CD20 monoclonal antibody, for treatment of rheumatoid arthritis with an inadequate response to one or more disease-modifying antirheumatic drugs: Results of a randomized, double-blind, placebo-controlled, phase I/II study. Arthritis Rheum 2010;62:2227−38. 19 Hagenbeek A, Gadeberg O, Johnson P, et al. First clinical use of ofatumumab, a novel fully human anti-CD20 monoclonal antibody in relapsed or refractory follicular lymphoma: results of a phase 1/2 trial. Blood 2008;111:5486−95. 20 Common Terminology Criteria for Adverse Events v3.0 (CTCAE). http://ctep.cancer.gov/protocolDevelopment/electronic _applications/ docs/ctcaev3.pdf. 21 Winkler U, Jensen M, Manzke O, et al. Cytokine-release syndrome in patients with B-cell chronic lymphocytic leukemia and high lymphocyte counts after treatment with an anti-CD20 monoclonal antibody (rituximab, IDEC-C2B8). Blood 1999;94:2217−24.

Souhrn

Ofatumumab je plně humánní monoklonální anti-CD20 protilátka, která prokázala významnou účinnost v léčbě chronické lymfocytární leukemie (CLL). Ve srovnání s první klinicky používanou anti-CD20 monoklonální protilátkou rituximabem vykazuje ofatumumab vyšší cytotoxicitu závislou na komplementu. Na základě výsledků velké mezinárodní studie III. fáze byla monoterapie ofatumumabem schválena regulačními úřady v Evropě i USA pro léčbu dvojitě refrakterní CLL (selhání léčby fludarabinem i alemtuzumabem). Nejčastější komplikací léčby ofatumumabem je infuzní a infekční toxicita, ale zpravidla se jedná o nežádoucí účinky mírného stupně. V současnosti probíhají klinické studie, které zkoumají účinnost a bezpečnost ofatumumabu v kombinované chemoimunoterapii a udržovací léčbě CLL, ale také dalších lymfoproliferací či revmatoidní artritidy.

Literatura

1
Smolej L. Modern concepts in the treatment of chronic lymphocytic leukemia. Hematology 2009;14:249−54. 2 Stashenko P, Nadler LM, Hardy R, et al. Characterization of a human B lymphocyte-specific antigen. J Immunol 1980; 125:1678−85. 3 Hallek M, Fischer K, Fingerle-Rowson G, et al. Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, phase 3 trial. Lancet 2010;376:1164−74. 4 Robak T, Dmoszynska A, Solal-Céligny P, et al. Rituximab plus fludarabine and cyclophosphamide prolongs progression-free survival compared with fludarabine and cyclophosphamide alone in previously treated chronic lymphocytic leukaemia. J Clin Oncol 2010;28:1756−65. 5 Teeling JL, French RR, Cragg MS, et al. Characterization of new human CD20 monoclonal antibodies with potent cytolytic activity against non-Hodgkin lymphomas. Blood 2004;104: 1793−800. 6 Glennie MJ, French RR, Cragg MS, et al. Mechanisms of killing by anti-CD20 monoclonal antibodies. Mol Immunol 2007;44: 3823−37. 7 Golay J, Lazzari M, Facchinetti V, et al. CD20 levels determine the in vitro susceptibility to rituximab and complement of B-cell chronic lymphocytic leukemia: further regulation by CD55 and CD59. Blood 2001;98:3383−9. 8 Teeling JL, Mackus WJ, Wiegman LJ, et al. The biological activity of human CD20 monoclonal antibodies is linked to unique epitopes on CD20. J Immunol 2006;177:362−71. 9 Robak T. Ofatumumab, a human monoclonal antibody for lymphoid malignancies and autoimmune disorders. Curr Opin Mol Ther 2008;10:294−309.
10
Ofatumumab summary of products characteristics. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/ human/001131/WC500093091.pdf
11
Bleeker WK, Munk ME, Mackus WJ, et al. Estimation of dose requirements for sustained in vivo activity of a therapeutic human anti-CD20 antibody. Br J Haematol 2008;140:303−12.
12
Coiffier B, Lepretre S, Pedersen LM, et al. Safety and efficacy of ofatumumab, a fully human monoclonal anti-CD20 antibody, in patients with relapsed or refractory B-cell chronic lymphocytic leukemia: a phase 1−2 study. Blood 2008;111: 1094−100.
13
Wierda WG, Kipps TJ, Mayer J, et al. Ofatumumab as single-agent CD20 immunotherapy in fludarabine-refractory chronic lymphocytic leukemia. J Clin Oncol 2010;28:1749−55.
14
Wierda WG, Kipps TJ, Durig J, et al. Chemoimmunotherapy with O-FC in previously untreated patients with chronic lymphocytic leukemia. Blood 2011;117:6450−8.
15
Hallek M, Fischer K, Fingerle-Rowson G, et al. Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, phase 3 trial. Lancet 201;376(9747):1164−74.
16
Faderl S, Wierda W, O’Brien S, et al. Fludarabine, cyclo-phosphamide, mitoxantrone plus rituximab (FCM-R) in frontline CLL < 70 Years. Leukemia Research 2010;34:284−8.
17
http://www.clinicaltrials.gov./ct2/results?term=ofatumumab +AND+CLL.
18
Østergaard M, Baslund B, Rigby W, et al. Ofatumumab, a human anti-CD20 monoclonal antibody, for treatment of rheumatoid arthritis with an inadequate response to one or more disease-modifying antirheumatic drugs: Results of a randomized, double-blind, placebo-controlled, phase I/II study. Arthritis Rheum 2010;62:2227−38.
19
Hagenbeek A, Gadeberg O, Johnson P, et al. First clinical use of ofatumumab, a novel fully human anti-CD20 monoclonal antibody in relapsed or refractory follicular lymphoma: results of a phase 1/2 trial. Blood 2008;111:5486−95.
20
Common Terminology Criteria for Adverse Events v3.0 (CTCAE). http://ctep.cancer.gov/protocolDevelopment/electronic _applications/ docs/ctcaev3.pdf.
21
Winkler U, Jensen M, Manzke O, et al. Cytokine-release syndrome in patients with B-cell chronic lymphocytic leukemia and high lymphocyte counts after treatment with an anti-CD20 monoclonal antibody (rituximab, IDEC-C2B8). Blood 1999;94:2217−24.

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