Seminars in Hematology
Volume 45, Issue 2 , Pages 75-84 , April 2008

Monoclonal Antibodies for the Treatment of Hematologic Malignancies: Schedule and Maintenance Therapy

  • Alden Moccia

      Affiliations

    • Corresponding Author InformationAddress correspondence to Alden Moccia, MD, Oncology Institute of Southern Switzerland (IOSI), Ospedale San Giovanni, CH-6600 Bellinzona, Switzerland.
    • ,
  • Michele Ghielmini

References 

  1. Maloney DG, Liles TM, Czerwinski DK, Waldichuk C, Rosenberg J, Grillo-Lopez A, et al. Phase I clinical trial using escalating single-dose infusion of chimeric anti-CD20 monoclonal antibody (IDEC-C2B8) in patients with recurrent B-cell lymphoma. Blood. 1994;84:2457–2466
  2. Rose AL, Smith BE, Maloney DG. Glucocorticoids and rituximab in vitro; synergistic direct antiproliferative and apoptotic effects. Blood. 2002;100:1765–1773
  3. Berinstein NL, Grillo-López AJ, White CA, Bence-Bruckler I, Maloney D, Czuczman M, et al. Association of serum Rituximab (IDEC-C2B8) concentration and anti-tumor response in the treatment of recurrent low-grade or follicular non-Hodgkin’s lymphoma. Ann Oncol. 1998;9:995–1001
  4. Maloney D, Grillo-Lopez A, Bodkin D, White C, Liles T, Royston I, et al. IDEC-C2B8: Results of a phase I multiple-dose trial in patients with relapsed non-Hodgkin’s lymphoma. J Clin Oncol. 1997;15:3266–3274
  5. McLaughlin P, Grillo-López AJ, Link BK, Levy R, Czuczman MS, Williams ME, et al. Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: Half of patients respond to a four-dose treatment program. J Clin Oncol. 1998;16:2825–2833
  6. Coiffier B, Haioun C, Ketterer N, Engert A, Tilly D, Johnson P, et al. Rituximab (anti-CD20 monoclonal antibody) for the treatment of patients with relapsing or refractory aggressive lymphoma: A multicenter phase II study. Blood. 1998;92:1927–1932
  7. O’Brien SM, Kantarjian H, Thomas DA, Giles FJ, Freirech EJ, Cortes J, et al. Rituximab dose-escalation trial in chronic lymphocytic leukemia. J Clin Oncol. 2001;19:2165–2170
  8. Manshouri T, Do K, Wang X, Giles FJ, O’Brien SM, Saffer H, et al. Circulating CD20 is detectable in the plasma of patients with chronic lymphocytic leukemia and is of prognostic significance. Blood. 2003;101:2507–2513
  9. Piro LD, White CA, Grillo-López AJ, Janakiraman N, Saven A, Beck TM, 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
  10. Bremer K. Semi-extended, six weekly rituximab infusions in pre-treated advanced low-grade B cell non-Hodgkin’s lymphoma: A phase II study. Anticancer Drugs. 2003;14:809–815
  11. Gordan LN, Grow WB, Pusateri A, Douglas V, Mendenhall NP, Lynch JW. Phase II trial of individualized rituximab dosing for patients with CD20-positive lymphoproliferative disorders. J Clin Oncol. 2005;23:1096–1102
  12. Czuczman MS, Grillo-López AJ, White CA, Saleh M, Gordon A, LoBuglio AF, et al. Treatment of patients with low-grade B-Cell lymphoma with the combination of chimeric anti-CD20 monoclonal antibody and CHOP chemotherapy. J Clin Oncol. 1999;17:268–276
  13. Byrd JC, Murphy T, Howard RS, Lucas MS, Goodrich A, Pearson M, 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
  14. Sehn LH, Donaldson J, Filewich A, Fitzgerald C, Gill KK, Runzer N, et al. Rapid infusion rituximab in combination with corticosteroid-containing chemotherapy or as maintenance therapy is well tolerated and can be safely be delivered in the community setting. Blood. 2007;109:4171–4173
  15. Salar A, Casao D, Cervera M, Pedro C, Calafell M, Abella E, et al. Rapid infusion of rituximab with or without steroid-containing chemotherapy: 1-yr experience in a single institution. Eur J Haematol. 2006;77:338–340
  16. Siano M, Lerch E, Zucca E, Mora O, Sessa C, Ghielmini M: A phase I–II study to determine the maximum tolerated infusion-rate of rituximab, with a special emphasis on monitoring the effect of rituximab on cardiac function. ASH abstr 3411.
  17. Hainsworth JD, Litschy S, Burris HA, Scullin DC, Corso SW, Yardley DA, et al. Rituximab as first-line and maintenance therapy for patients with indolent non-Hodgkin’s lymphoma. J Clin Oncol. 2002;20:4261–4267
  18. Hainsworth JD, Litschy S, Lamb MR, Rodriguez GI, Scroggin C, Greco FA. 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
  19. Hainsworth JD, Litchy S, Shaffer DW, Lackey VL, Grimaldi M, Greco FA. Maximizing therapeutic benefit of rituximab: Maintenance therapy versus re-treatment at progression in patients with indolent non-Hodgkin’s lymphoma: A randomized phase II trial of the Minnie Pearl Cancer Research Network. J Clin Oncol. 2005;23:1088–1095
  20. Ghielmini M, Hsu-Schmitz SF, Cogliatti SB, Pichert G, Hummerjohann J, Walzer U, et al. Prolonged treatment with rituximab in patients with follicular lymphoma significantly increases event-free survival and response duration compared with the standard weekly × 4 schedule. Blood. 2004;103:4416–4423
  21. Ghielmini M, Hsu-Schmitz S, Cogliatti S, Bertoni F, Waltzer U, Fey MF, et al. Effect of single-agent Rituximab given at the standard schedule or as prolonged treatment in patients with mantle cell lymphoma: A study of the Swiss Group for Clinical Cancer Research (SAKK). J Clin Oncol. 2005;4:705–711
  22. Hochster HS, Weller E, Ryan T, Habermann TM, Gascoyne R, Frankel SR, et al. Results of E1496: A phase III trial of CVP with or without maintenance rituximab in advanced indolent lymphoma (NHL). J Clin Oncol. 2004;22(suppl):558s;(abstr)
  23. Hochster HS, Weller E, Gascoyne RD, Ryan TS, Habermann TM, Gordon LI, et al. Maintenance rituximab after CVP results in superior clinical outcome in advanced follicular lymphoma (FL): Results of the E1496 phase III trial from the Eastern Cooperative Oncology Group and the Cancer and Leukemia Group B. Blood. 2005;106:106a;(abstr)
  24. Hagenbeek A, Van Glabbeke M, Teodorovic I, et al. The role of rituximab maintenance treatment in relapsed follicular NHL: An interim analysis of the EORTC randomized intergroup trial. Ann Oncol. 2005;16:v52;(abstr)
  25. Habermann TM, Weller E, Morrison VA, et al. Rituximab-CHOP versus CHOP with or withou maintenance rituximab in patients 60 years of age or older with diffuse large B-cell lymphoma (DLBCL): An update. Blood. 2004;104:40a;(abstr 127)
  26. Forstpointner R, Dreyling M, Repp R, Hermann S, Hanel A, Metzner B, et al. The addition of rituximab to a combination of fludarabine, cyclophosphamide and mitoxantrone (FCM) significantly prolongs survival as compared with FCM alone in patients with relapsed and refractory follicular and mantle cell lymphoma—Results of a prospective randomized study of the German Low Grade Lymphoma Study Group. Blood. 2004;104:3064–3071
  27. van Oers MHJ, Klasa R, Marcus RE, Wolf M, Kimby E, Gascoyne RD, et al. Rituximab maintenance improves clinical outcome of relapsed/resistant follicular non-Hodgkin’s lymphoma, both in patients with and without rituximab during induction: Results of a prospective randomized phase III intergroup trial. Blood. 2006;108:3295–3301
  28. Brugger W, Hirsch J, Grüneback F, Repp R, Brossart P, Vogel W, et al. Rituximab consolidation after high-dose chemotherapy and autologous blood stem cell transplantation in follicular and mantle cell lymphoma: A prospective multicenter phase II study. Ann Oncol. 2004;15:1691–1698
  29. Mangel J, Leitch HA, Connors JM, Buckstein R, Imrie K, Spaner D, et al. Intensive chemotherapy and autologous stem-cell transplantation plus rituximab is superior to conventional chemotherapy for newly diagnosed advanced stage mantle cell lymphoma: A matched pair analysis. Ann Oncol. 2004;15:283–290
  30. Neumann F, Harnsen S, Martin S, Kronenwett R, Kondakei M, Aivado M, et al. Rituximab long-term maintenance therapy after autologous stem cell transplantation in patients with B cell non-Hodgkin’s lymphoma. Ann Hematol. 2006;85:530–534
  31. Gilleece MH, Dexter TM. Effect of Campath-H1 antibody on human hematopoietic progenitors in vitro. Blood. 1993;82:807–812
  32. Heit W, Bunjes D, Wiesneth M, Schmeiser T, Arnold R, Hale G, et al. Ex vivo T cell depletion with the monoclonal antibody Campath-1 plus human complement effectively prevents acute graft versus-host disease in allogeneic bone marrow transplantation. Br J Haematol. 1986;64:479–486
  33. Dyer MJ, Hale G, Hayhoe FG, Waldmann H. Effects of CAMPATH-1 antibodies in vivo in patients with lymphoid malignancies: influence of antibody isotype. Blood. 1989;73:1431–1439
  34. Rowan W, Tite J, Topley P, Brett SJ. Cross-linking of the CAMPATH-1 antigen (CD52) mediates growth inhibition in human B- and T-lymphoma cell lines, and subsequent emergence of CD52-deficient cells. Immunology. 1998;95:427–436
  35. Xia MQ, Hale G, Waldmann H. Efficient complement-mediated lysis of cells containing the CAMPATH-1 (CDw52) antigen. Mol Immunol. 1993;30:1089–1096
  36. Riechmann L, Clark M, Waldmann H, Winter G. Reshaping human antibodies for therapy. Nature. 1988;332:323–327
  37. Golay J, Manganini M, Rambaldi A, Introna M. Effect of alemtuzumab on neoplastic B cells. Haematologica. 2004;89:1476–1483
  38. Mould DR, Baumann A, Kuhlmann J, Keating MJ, Weitman S, Hillmen , et al. Population pharmacokinetics-pharmacodynamics of alemtuzumab (Campath) in patients with chronic lymphocytic leukemia and its link to treatment response. Br J Clin Pharmacol. 2007;64:278–291
  39. Montillo M, Tedeschi A, Miqueleiz S, Veronese S, Cairoli R, Intropido L, et al. Alemtuzumab as consolidation after a response to fludarabine is effective in purging residual disease in patients with chronic lymhpocytic leucemia. J Clin Oncol. 2006;24:2337–2342
  40. Hale G, Dyer MJS, Clark MR, Philipps JM, Marcus R, Riechmann L, et al. Remission induction in non-Hodgkin lymphoma with reshaped human antibody CAMPATH-1H. Lancet. 1988;2:1394–1399
  41. Osterborg A, Dyer MJ, Bunjes D, Pangalis GA, Bastion Y, Catovsky D, et al. Phase II multicenter study of human CD52 antibody in previously treated chronic lymphocytic leukemia (European Study Group of CAMPATH-1H Treatment in Chronic Lymphocytic Leukemia). J Clin Oncol. 1997;15:1567–1574
  42. Rai KR, Freter CE, Mercier RJ, Cooper MR, Mitchell BS, Stadtmauer EA, et al. Alemtuzumab in previously treated chronic lymphocytic leukemia patients who also had received fludarabine. J Clin Oncol. 2002;20:3891–3897
  43. Keating MJ, Flinn I, Jain V, Binet JL, Hillmen P, Byrd J, 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
  44. Pawson R, Dyer MJS, Barge R, Matutes E, Thomton PD, Emmett E, et al. Treatment of T-cell prolymphocytic leukemia with human CD52 antibody. J Clin Oncol. 1997;15:2667–2672
  45. Dearden CE, Matutes E, Cazin B, Tjonnfjord GE, Parreira A, Nomdedeu B, et al. High remission rate in T-cell prolymphocytic leukemia with CAMPATH-1H. Blood. 2001;98:1721–1726
  46. Keating MJ, Cazin B, Coutré S, Birhray R, Kovacsovics T, Langer B, et al. Campath-1H treatment of T-cell prolymphocytic leukemia in patients for whom at least one prior chemotherapy regimen has failed. J Clin Oncol. 2001;20:205–213
  47. Enblad G, Hagberg H, Erlanson M, Lundin J, MacDonald AP, Repp R, et al. A pilot study of alemtuzumab (anti-CD52 monoclonal antibody) therapy for patients with relapsed or chemotherapy-refractory peripheral T-cell lymphomas. Blood. 2004;103:2920–2924
  48. Zinzani PL, Alinari L, Tani M, Fina M, Pileri S, Baccarani M. Preliminary observations of a phase II study of reduced-dose alemtuzumab in patients with pretreated T-cell lymphoma. Haematologica. 2005;90:702–703
  49. Cull G, Haynes AP, Byrne JL, Carter GI, Miflin G, Rebello P, et al. Preliminary experience of allogeneic stem cell transplantation for lymphoproliferative disease using BEAM-CAMPATH conditioning: an effective regimen with low procedure related toxicity. Br J Haematol. 2000;108:754–760
  50. Hale G, Rebello P, Brettman LR, Fegan C, Kennedy B, Kimby E, 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
  51. Lundin J, Kimby E, Bjorkholm M, Broliden PA, Celsing F, Hjalmar V, 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
  52. Bowen AL, Zomas A, Emmett E, Matutes E, Dyer MJ, Catovsky D. Subcutaneous CAMPATH-1H in fludarabine-resistant/relapsed chronic lymphocytic and B-prolymphocytic leukemia. Br J Haematol. 1997;96:617–619
  53. Rai KR, Jonson D, Driscoll N, Crowley A, Ahmed S. Varyng modes of maintenance therapy with CAMPATH-1H in chronic lymphocytic leukemia. Proc Am Soc Clin Oncol. 2002;21:275a;(abstr)
  54. Wendtner CM, Ritgen M, Schweighofer CD, Fingerle-Rowson G, Campe H, Jager G, et al. Consolidation with alemtuzumab in patients with chronic lymphocytic leukemia (CLL) in first remission: Experience on safety and efficacy within a randomized multicenter phase III trial of the German CLL Study Group (GCLLSG). Leukemia. 2004;18:1093–1101
  55. O’Brien SM, Kantarjian HM, Thomas DA, Cortes J, Giles FJ, Wierda WG, et al. Alemtuzumab as treatment for residual disease after chemotherapy in patients with chronic lymphocytic leukemia. Cancer. 2003;98:2657–2663
  56. Linenberger ML, Hong T, Flowers D, Sievers EL, Gooley TA, Bennett MS, et al. Multidrug-resistance phenotype and clinical responses to gemtuzumab ozogamicin. Blood. 2001;98:988–994
  57. Sievers EL, Larson RA, Stadtmauer EA, Estey E, Lowenberg B, Dombret H, et al. Efficacy and safety of gemtuzumab ozogamicin in patients with CD33-positive acute myeloid leukaemia in first relapse. J Clin Oncol. 2001;19:3244–3254
  58. Golay J, Di Gaetano N, Amico D, Cittera E, Barbui AM, Giavazzi R, et al. Gemtuzumab ozogamicin (Mylotarg) has therapeutic activity against CD33+ acute lymphoblastic leukaemias in vitro and in vivo. Br J Haematol. 2005;128:310–317
  59. Amico D, Barbui AM, Erba E, Rambaldi A, Introna M, Golay J. Differential response of human acute myeloid leukemia cells to gemtuzumab ozogamicin in vitro: Role of Chk1 and Chk2 phosphorylation and caspase 3. Blood. 2003;101:4589–4597
  60. Sievers EL, Appelbaum FR, Spielberger RT, Forman SJ, Flowers D, Smith FO, et al. Selective ablation of acute myeloid leukemia using antibodytargeted chemotherapy: A phase I study of an anti-CD33 calicheamicin immunoconjugate. Blood. 1999;93:3678–3684
  61. Sievers EL, Larson RA, Stadtmauer EA, Estey E, Lowenberg B, Dombret H, et al. Efficacy and safety of gemtuzumab ozogamicin in patients with CD33-positive acute myeloid leukemia in first relapse. J Clin Oncol. 2001;19:3244–3254
  62. Taksin AL, Legrand O, Raffoux E, de Revel T, Thomas X, Contentin N, et al. High efficacy and safety profile of fractionated doses of Mylotarg as induction therapy in patients with relapsed acute myeloblastic leukemia: A prospective study of the Alfa group. Leukemia. 2007;21:66–71
  63. van der Velden VHJ, te Marvelde JG, Hoogeveen PG, Bernstein ID, Houtsmuller AB, Berger AS, et al. Targeting of the CD33- calicheamicin immunoconjugate Mylotarg (CMA-676) in acute myeloid leukemia: In vivo and in vitro saturation and internalization by leukemic and normal myeloid cells. Blood. 2001;97:3197–3204
  64. Dowell JA, Korth-Bradley J, Liu H, King SP, Berger MS. Pharmacokinetics of gemtuzumab ozogamicin, an antibody-targeted chemotherapy agent for the treatment of patients with acute myeloid leukemia in first relapse. J Clin Pharmacol. 2001;41:1206–1214
  65. Thomas X, Le QH, Tavernier E, Mahmoudi S, Chelghoum Y, Nicolini F, et al. Gemtuzumab ozogamicin (Mylotargs) as single agent treatment for adult patients with acute myeloid leukemia (AML). Blood. 2005;106:4598;(abstr)
  66. Larson RA, Boogaerts M, Estey E, Karanes C, Stadtmauer EA, Sievers EL, et al. Antibody-targeted chemotherapy of older patients with acute myeloid leukemia in first relapse using Mylotarg (gemtuzumab ozogamicin). Leukemia. 2002;16:1627–1636
  67. Lundin J, Österborg A, Brittinger G, Crowther D, Dombret A, Engert A, et al. CAMPATH-1H monoclonal antibody in therapy for previous treated low-grade non-Hodgkin’s lymphomz: A phase II multicenter study. J Clin Oncol. 1998;16:3257–3262
  68. Montillo M, Cafro AM, Tedeschi A, Brando B, Oreste P, Veronese S, et al. Safety and efficacy of subcutaneous Campath-1H for treating residual disease in patients with chronic lymphocytic leucemia responding to fludarabine. Haematologica. 2002;87:695–700
  69. Moreton P, Kennedy B, Lucas G, Leach M, Rassam SMB, Haynes A, et al. Eradication of minimal residual disease in B-cell chronic lymhocytic leukemia after alemtuzumab therapy is associated with prolonged survival. J Clin Oncol. 2005;23:2971–2979
  70. Piccaluga PP, Martinelli G, Rondoni M, Malagola M, Gaitani S, Isidori A, et al. Gemtuzumeb ozogamicin for relapsed and refractory acute myeioid leukemia and myeloid sarcomas. Leuk Lymphoma. 2004;45:1791–1795
  71. Larson RA, Sievers EL, Stadtmauer EA, Lowenberg B, Estey EH, Dombret H, et al. Final report of the efficacy and safety of gemtuzumab ozogamicin in patients with CD33-positive acute myelcid leukemia in first recurrence. Cancer. 2005;104:1442–1452
  72. Amadori S, Suciu S, Stasi R, Willemze R, Mandelli F, Sellesiag D, et al. Gemtuzumab ozogamicin as single-agent treatment for frail patients 61 years of age and older with acute myeloid leukemia: Final results of AML-15B, a phase 2 study of the European Organisation for Research and Treatment of Cancer and Gruppo Italiano Malattie Ematologiche dell’Adulto Leucemia Groups. Leukemia. 2005;19:1768–1773
  73. Nebhan C, Rundhaugen LM, Riley MB, Rademaker A, Boehike L, Jatoi M, et al. Phase II pilot trial of gemtuzumab ozogamicin (GO) as first line therapy in acute myeloid leukemia patients age 65 or older. Leuk Res. 2005;29:53–57
  74. Van der Heiden PL, Jedema I, Willemze R, Barge RM. Efficacy and toxicity of gemtuzumab ozogamicin in patients with acute myeloid leukemia. Eur J Haematol. 2006;76:409–413

PII: S0037-1963(08)00007-3

doi: 10.1053/j.seminhematol.2008.02.006

Seminars in Hematology
Volume 45, Issue 2 , Pages 75-84 , April 2008

Article Tools