Best Practice & Research Clinical Haematology
Volume 23, Issue 1 , Pages 133-143 , March 2010

Monoclonal antibody therapy of chronic lymphocytic leukaemia

  • Bruce D. Cheson, MD (Professor of Medicine, Head of Haematology)

      Affiliations

    • Corresponding Author InformationTel.: +1 202 444 7932; Fax: +1 202 444 1229.

References 

  1. Eichhorst B, Busch R, Hopfinger G, et al. Fludarabine plus cyclophosphamide versus fludarabine alone in first-line therapy of younger patients with chronic lymphocytic leukemia. Blood. 2006;107:885–891
  2. Flinn IW, Neuberg DS, Grever MR, et al. Phase III trial of fludarabine plus cyclophosphamide compared with fludarabine for patients with previously untreated chronic lymphocytic leukemia: US Intergroup Trial E2997. J Clin Oncol. 2007;25:793–798
  3. Ehrlich P. On immunity with special reference to the cell of life. Proc Royal Soc London. 1900;66:424–448
  4. Kohler G, Milstein C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature. 1975;256:495–497
  5. Nadler LM, Ritz J, Hardy R, et al. A unique cell surface antigen identifying lymphoid malignancies of B cell origin. J Clin Invest. 1981;67:134–140
  6. Dillman RO, Shawler DL, Dillman JB, et al. Therapy of chronic lymphocytic leukemia and cutaneous T-cell lymphoma with T101 monoclonal antibody. J Clin Oncol. 1984;2:881–891
  7. Dillman RO, Beauregard J, Shawler DL, et al. Continuous infusion of T101 monoclonal antibody in chronic lymphocytic leukemia and cutaneous T-cell lymphoma. J Biol Response Mod. 1986;5:394–410
  8. Hertler AA, Schlossman DM, Borowitz MJ, et al. A phase I study of T101-ricin A chain immunotoxin in refractory chronic lymphocytic leukemia. J Biol Response Mod. 1988;7:97–113
  9. Laurent G, Pris J, Farcet J-P, et al. Effects of therapy with T101 ricin A-chain immunotoxin in two leukemia patients. Blood. 1986;67:1680–1687
  10. Capel PJA, Preijers FWMB, Allebes WA, et al. Treatment of chronic lymphocytic leukaemia with monoclonal anti-idiotype antibody. Neth J Med. 1985;28:112–118
  11. Hale G, Xia M-Q, Tighe HP, et al. The CAMPATH-1 antigen (CDw52). Tissue Antigens. 1990;35:118–127
  12. Ginaldi L, De martinis M, Matutes E, et al. Levels of expression of CD52 in normal and leukemic B and T cells: correlation with in vivo therapeutic responses to CAMPATH-1H. Leuk Res. 1998;22:185–191
  13. Dyer MJS, Hale G, Hayhoe FGJ, et al. Effects of CAMPATH-1 antibodies in vivo in patients with lymphoid malignancies: Influence of antibody isotype. Blood. 1989;73:1431–1439
  14. Österborg A, Dyer MJS, Bunjes D, et al. Phase II multicenter study of human CD52 antibody in previously treated chronic lymphocytic leukemia. J Clin Oncol. 1997;15:1567–1574
  15. Keating MJ, Flinn I, Jain V, et al. Therapeutic role of alemtuzumab (CAMPATH-1H) in patients who have failed fludarabine: results of a large international study. Blood. 2002;99:3554–3561
  16. Hillmen P, Skotnicki AB, Robak T, et al. Alemtuzumab compared with chlorambucil as first-line therapy for chronic lymphocytic leukemia. J Clin Oncol. 2007;25:5616–5623
  17. Lundin J, Kimby E, Björkholm M, et al. Phase II trial of subcutaneous anti-CD52 monoclonal antibody alemtuzumab (CAMPATH-1H) as first-line treatment for patients with B-cell chronic lymphocytic leukemia (B-CLL). Blood. 2002;100:768–773
  18. Hale G, Rebello P, Breitman LR, et al. Blood concentrations of alemtuzumab and antiglobulin responses in patients with chronic lymphocytic leukemia following intravenous or subcutaneous routes of administration. Blood. 2004;104:948–955
  19. Rai KR, Byrd JC, Peterson B, et al. Subcutaneous alemtuzumab following fludarabine for previously untreated patients with chronic lymphocytic leukemia (CLL): CALGB study 19901. Blood. 2003;102(Suppl. 1):676–677a[abstract 2506]
  20. Rai KR, Byrd JC, Peterson B, et al. A phase II trial of fludarabine followed by alemtuzumab (CAMPATH-1H) in previously untreated chronic lymphocytic leukemia (CLL) patients with active disease: Cancer and Leukemia Group B (CALGB) Study 19901. Blood. 2002;100(Suppl. 1):205a;[abstract 772]
  21. Kennedy B, Rawstron A, Carter C, et al. CAMPATH-1H and fludarabine in combination are highly active in refractory chronic lymphocytic leukemia. Blood. 2002;99:2245–2247
  22. Elter T, Bochmann P, Schulz H, et al. FluCam - a new, 4-weekly combination of fludarabine and alemtuzumab for patients with relapsed chronic lymphocytic leukemia. Blood. 2004;104(Suppl. 1):690a;[abstract 2517]
  23. Engert A, Gercheva L, Robak T, et al. Improved progression-free survival (PFS) of alemtuzumab (Campath®, MabCampath®) plus fludarabine (Fludara®) versus fludarabine alone as second-line treatment of patients with B-cell chronic lymphocytic leukemia: preliminary results from a phase III randomized trial. Blood. 2009;114(22):224–225[abstract 537]
  24. Badoux XC, Keating M, O'Brien S, et al. Chemoimmunotherapy with cyclophosphamide, fludarabine, alemtuzumab and rituxiamb (CFAR) is effective in relapsed patients with chronic lymphocytic leukemia (CLL). Blood. 2009;114(22):1332–1333[abstract 34.31]
  25. Moreton P, Kennedy B, Lucas G, et al. Eradication of minimal residual disease in B-cell chronic lymphocytic leukemia after alemtuzumab therapy is associated with prolonged survival. J Clin Oncol. 2005 May 1;23:2971–2979
  26. Montillo M, Tedeschi A, Rossi V, et al. Successful CD34+ cell mobilization by intermediate-dose ara-C in chronic lymphocytic leukemia patients treated with sequential fludarabine and CAMPATH-1H. Leukemia. 2003;18:57–62
  27. O'Brien SM, Kantarjian HM, Thomas DA, et al. Alemtuzumab as treatment for residual diseasee after chemotherapy on patients with chronic lymphocytic leukemia. Cancer. 2003;98:2657–2663
  28. Lin TS, Donahue KA, Byrd JC, et al. Consolidation therapy with subcutaneous (SC) alemtuzumab after fludarabine and rituximab (FR) induction therapy improves the complete response (CR) rate in chronic lymphocytic leukemia (CLL) and eradicates minimal residual disease (MRD) but is associated with severe infecious toxicity: final analysis of CALGB study 10101. Blood. 2009;114(22):92;[abstract 210]
  29. Schweighofer CD, Ritgen M, Eichhorst BF, et al. Consolidation with alenmtuzumab improves progression-free survival in patients with chronic lymphocytic leukaemia (CLL) in first clinical remission: long-term follow-up of a randomized phase III trial of the German CLL Study Group (GCLLSG). Br J Haematol. 2009;144:95–98
  30. Stilgenbauer S, Döhner H. Campath-1H-induced complete remission of chronic lymphocytic leukemia despite p53 mutation and resistance to chemotherapy. N Engl J Med. 2002;347:452
  31. Maloney DG, Grillo-López AJ, White CA, et al. IDEC-C2B8 (Rituximab) anti-CD20 monoclonal antibody therapy in patients with relapsed low-grade non-Hodgkin's lymphoma. Blood. 1997 Sep 15;90:2188–2195
  32. Piro LD, White CA, Grillo-Lopez AJ, et al. Extended rituximab (anti-CD20 monoclonal antibody) therapy for relapsed or refractory low-grade or follicular non-Hodgkin's lymphoma. Ann Oncol. 1999;10:655–661
  33. 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;94:2217–2224
  34. Foran JM, Rohatiner AZ, Cunningham D, et al. European phase II study of rituximab (Chimeric anti-CD20 monoclonal antibody) for patients with newly diagnosed mantle-cell lymphoma and previously treated mantle-cell lymphoma, immunocytoma, and small B-cell lymphocytic lymphoma. J Clin Oncol. 2000;18:317–324
  35. Hainsworth JD, Litchy S, Barton JH, et al. Single-agent rituximab as first-line and maintenance treatment for patients with chronic lymphocytic leukemia or small lymphocytic lymphoma: a phase II trial of the Minnie Pearl Cancer Research Network. J Clin Oncol. 2003;21:1746–1751
  36. Hegde UP, Wilson WH, White T, et al. Rituximab treatment of refractory fludarabine -associated immune thrombocytopenia in chronic lymphocytic leukemia. Blood. 2002;100:2260–2262
  37. Byrd JC, Murphy T, Howard RS, et al. Rituximab using a thrice weekly dosing schedule in B-cell chronic lymphocytic leukemia and small lymphocytic lymphoma demonstrates clinical activity and acceptable toxicity. J Clin Oncol. 2001;19:2153–2164
  38. O'Brien SM, Kantarjian H, Thomas DA, et al. Rituximab dose-escalation trial in chronic lymphocytic leukemia. J Clin Oncol. 2001;19:2165–2170
  39. Byrd JC, Peterson B, Morrison VA, et al. Randomized phase 2 study of fludarabine with concurrent versus sequential treatment with rituximab in symptomatic, untreated patients with B-cell chronic lymphocytic leukemia: results from Cancer and Leukemia Group B 9712 (CALGB 9712). Blood. 2003;101:6–14
  40. Woyach JA, Ruppert AS, Heerema NA, et al. Treatment with fludarabine and rituximab produces extended overall survival (OS) and progession-free survival (PFS) in chronic lymphocytic leukemia (CLL) without increased risk of secondary malignancy: long-term follow-up of CALGB study 9712. Blood. 2009;114(22):226;[abstract 540]
  41. Keating MJ, O'Brien S, Albitar M, et al. Early results of a chemoimmunotherapy regimen of fludarabine, cyclophosphamide, and rituximab (FCR) as initial therapy for chronic lymphocytic leukemia. J Clin Oncol. 2005;23:4079–4088
  42. Tam CS, O'Brien S, Wierda W, et al. Long-term results of the fludarabine, cyclophosphamide, and rituximab regimen as initial therapy of chronic lymphocytic leukemia. Blood. 2008;112:975–980
  43. Wierda W, O'Brien S, Wen S, et al. Chemoimmunotherapy with fludarabine, cyclophosphamide and rituximab for relapsed and refractory chronic lymphocytic leukemia. J Clin Oncol. 2005;23:4070–4078
  44. Hallek M, FIngerle-Rowson G, Fink AM, et al. First-line treatment with fludarabine (F), cyclophosphamide (C), and rituximab (R) (FCR) improves overall survival (OS) in previously untreated patients (pts) with advanced chronic lymphocytic leukemia (CLL): Results of a randomized phase III trial on behalf of an international group of investigators and the German CLL Study Group. Blood. 2009;114(22):223–224[abstract 535]
  45. 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 leukemia. J Clin Oncol. 2010 Apr 1;28:1756–1765
  46. Lepretre S, Aurran T, Mahe B, et al. Immunochemotherapy with fludarabine (F), cyclophosphamide (C), and rituximab (R) (FCR) versus fludarabine (F), cyclophosphamide (C) amd MabCampath (Cam) (FCCam) in previouslhy untreated patients (pts) with advanced B-chronic lymphocytic leukemia (B-CLL): experience on safety and efficacy within a randomised multicenter phase III trail of the French Cooperative Group on CLL and WM (FCGCLL/WM) and the “Groupe Oueste-Est d'Etudes des Leucémies Aigües et Autres Maladies du Sang” (GOELAMS): CLL2007FMP (for fit medically patients). Blood. 2009;114(22):225;[abstract 538]
  47. Nabhan C, Tallman MS, Riley MB, et al. Phase I study of rituximab and CAMPATH-1H in patients with relapsed or refractory chronic lymphocytic leukemia. Blood. 2001;98(Suppl. 1):365a;[abstract 1536]
  48. Faderl S, Ferragoli A, Wierda WG, et al. The combination of alemtuzumab continuous intravenous infusion (civ) followed by subcutaneous injection (sc) plus rituximab has activity in patients (pts) with relapsed chronic lyhmphocytic leukemia (CLL). Blood. 2006;108(part 1):800a;[abstract 2827]
  49. Maloney DG, Grillo-López AJ, White CA, et al. IDEC-C2B8 (Rituximab) anti-CD20 monoclonal antibody therapy in patients with relapsed low-grade non-Hodgkin's lymphoma. Blood. 1997 Sep 15;90:2188–2195
  50. McLaughlin P, Grillo-López AJ, Link BK, et al. Rituximab chimeric anti-CD20 monoclonal antibody therapy of relapsed indolent lymphoma: half of patients respond to a four-dose treatment program. J Clin Oncol. 1998;16:2825–2833
  51. Byrd JC, Waselenko JK, Maneatis T, et al. Rituximab therapy in hematologic malignancy patients with circulating tumor cells: association with increased infusion-related side effects and rapid blood tumor clearance. J Clin Oncol. 1999;17:791–795
  52. 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;104:1793–1800
  53. 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;111:1094–1100
  54. Wierda W, Kipps T, Mayer J, et al. High activity of single-agent ofatumumab, a novel CD20 monoclonal antibody, in fludarabine- and alemtuzumab-refractory or bulky fludarabine-refractory chronic lymphocytic leukemia. Haematologica. 2009;94(Suppl. 2):373;[abstract 0928]
  55. Morchhauser F, Cartron G, Lamy T, et al. Phase I study of RO5072759 (GA101) in relapsed/refractory chronic lymphocytic leukemia. Blood. 2009;114(22):364;[abstract 884]
  56. Byrd JC, O'Brien S, Flinn IW, et al. Phase I study of lumiliximab with detailed pharmacokinetic and pharmacodynamic measurements in patients with relapsed or refractory chronic lymphocytic leukemia. Clin Cancer Res. 2007;13(15 Pt 1):4448–4455
  57. Byrd J, Castro J, Flinn I, et al. Lumiliximab in combination with FCR for the treatment of relapsed chronic lymphocytic leukemia (CLL): results from a phase I/II multicenter study. Ann Oncol. 2008;19(Suppl. 4):[abstract 145]
  58. Zhao X, Lapalombella R, Joshi T, et al. Targeting CD37-positive lymphoid malignancies with a novel engineered small modular immunopharmaceutical. Blood. 2007;110:2569–2577
  59. Baum PR, Cerveny C, Gordon B, et al. Evaluation of the effect of TRU-16, an anti-CD37 directed SMIP in combination with other therapeutic drugs in models of non-Hodgkin's lymphoma. J Clin Oncol. 2009;27(15s):451s;[abstract 8571]
  60. Andritsos A, Furman RR, Flinn IW, et al. A phase 1 trial of TRU-016, an anti-CD37 small modular immunopharmaceutical (SMIP™) proteein in relapsed and refractory CLL: early promising clinical activity. Blood. 2009;114(22):1330;[abstract 3124]
  61. Stilgenbauer S, Zenz T, Winkler D, et al. Subcutaneous alemtuzumab in fludarabine-refractory chronic lymphocytic leukemia: clinical results and prognostic marker analyses from the CLL2H study of the German Chronic Lymphocytic Leukemia Study Group. J Clin Oncol. 2009;27(24):3994–4001

PII: S1521-6926(10)00007-1

doi: 10.1016/j.beha.2010.01.006

Best Practice & Research Clinical Haematology
Volume 23, Issue 1 , Pages 133-143 , March 2010

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