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Novel Therapeutic Strategies in Adult Acute Lymphoblastic Leukemia – A Focus on Emerging Monoclonal Antibodies

  • Acute Leukemias (F Ravandi, Section Editor)
  • Published:
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Abstract

The outcomes in adult B-cell acute lymphoblastic leukemia (ALL) remain inferior to those achieved in pediatric populations. Targeted therapy with monoclonal antibodies may improve outcomes in adult B-cell ALL without significant additive toxicity. Rituximab is the best known monoclonal antibody and is routinely used in combination chemo-immunotherapy for treatment of adult B-cell ALL and Burkitts leukemia. A number of other monoclonal antibodies are currently under investigation for treatment of adult B-cell ALL including unconjugated antibodies (eg., ofatumumab, alemtuzumab and epratuzumab), antibodies conjugated to cytotoxic agents (eg., inotuzumab ozogamycin and SAR3419), antibodies conjugated to toxins such Pseudomonas or Diptheria toxins (eg., BL22 and moxetumomab pasudotox), and T-cell engaging bi-specific antibodies that redirect cytotoxic T lymphocytes to lyse target ALL cells (eg., blinatumomab). In this article we review the therapeutic implications, current status and results of monoclonal antibody-based therapy in adult B-cell ALL.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2006. CA Cancer J Clin. 2006;56:106–30.

    Article  PubMed  Google Scholar 

  2. Pui CH, Evans WE. Acute lymphoblastic leukemia. N Engl J Med. 1998;339:605–15.

    Article  PubMed  CAS  Google Scholar 

  3. Pui CH, Evans WE. Treatment of acute lymphoblastic leukemia. N Engl J Med. 2006;354:166–78.

    Article  PubMed  CAS  Google Scholar 

  4. Pui CH, Robison LL, Look AT. Acute lymphoblastic leukaemia. Lancet. 2008;371:1030–43.

    Article  PubMed  CAS  Google Scholar 

  5. Pui CH, Carroll WL, Meshinchi S, et al. Biology, risk stratification, and therapy of pediatric acute leukemias: an update. Journal of clinical oncology: official journal of the American Society of Clinical Oncology. 2011;29:551–65.

    Article  Google Scholar 

  6. Gaynon PS, Trigg ME, Heerema NA, et al. Children's Cancer Group trials in childhood acute lymphoblastic leukemia: 1983-1995. Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund UK. 2000;14:2223–33.

    Article  CAS  Google Scholar 

  7. Faderl S, O'Brien S, Pui CH, et al. Adult acute lymphoblastic leukemia: concepts and strategies. Cancer. 2010;116:1165–76.

    Article  PubMed  CAS  Google Scholar 

  8. Larson RA. The U.S. trials in adult acute lymphoblastic leukemia. Ann Hematol. 2004;83 Suppl 1:S127–128.

    PubMed  Google Scholar 

  9. Hunault M, Harousseau JL, Delain M, et al. Better outcome of adult acute lymphoblastic leukemia after early genoidentical allogeneic bone marrow transplantation (BMT) than after late high-dose therapy and autologous BMT: a GOELAMS trial. Blood. 2004;104:3028–37.

    Article  PubMed  CAS  Google Scholar 

  10. Kantarjian H, Thomas D, O'Brien S, et al. Long-term follow-up results of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (Hyper-CVAD), a dose-intensive regimen, in adult acute lymphocytic leukemia. Cancer. 2004;101:2788–801.

    Article  PubMed  CAS  Google Scholar 

  11. Bassan R, Hoelzer D. Modern therapy of acute lymphoblastic leukemia. Journal of clinical oncology: official journal of the American Society of Clinical Oncology. 2011;29:532–43.

    Article  Google Scholar 

  12. Gokbuget N, Hoelzer D, Arnold R, et al. Treatment of Adult ALL according to protocols of the German Multicenter Study Group for Adult ALL (GMALL). Hematol Oncol Clin North Am. 2000;14:1307–25. ix.

    Article  PubMed  CAS  Google Scholar 

  13. Pulte D, Gondos A, Brenner H. Improvement in survival in younger patients with acute lymphoblastic leukemia from the 1980s to the early 21st century. Blood. 2009;113:1408–11.

    Article  PubMed  CAS  Google Scholar 

  14. Rowe JM, Buck G, Burnett AK, et al. Induction therapy for adults with acute lymphoblastic leukemia: results of more than 1500 patients from the international ALL trial: MRC UKALL XII/ECOG E2993. Blood. 2005;106:3760–7.

    Article  PubMed  CAS  Google Scholar 

  15. Arico M, Valsecchi MG, Camitta B, et al. Outcome of treatment in children with Philadelphia chromosome-positive acute lymphoblastic leukemia. N Engl J Med. 2000;342:998–1006.

    Article  PubMed  CAS  Google Scholar 

  16. Huguet F, Leguay T, Raffoux E, et al. Pediatric-inspired therapy in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia: the GRAALL-2003 study. Journal of clinical oncology: official journal of the American Society of Clinical Oncology. 2009;27:911–8.

    Article  CAS  Google Scholar 

  17. Storring JM, Minden MD, Kao S, et al. Treatment of adults with BCR-ABL negative acute lymphoblastic leukaemia with a modified paediatric regimen. British journal of haematology. 2009;146:76–85.

    Article  PubMed  Google Scholar 

  18. O'Brien S, Thomas DA, Ravandi F, et al. Results of the hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone regimen in elderly patients with acute lymphocytic leukemia. Cancer. 2008;113:2097–101.

    Article  PubMed  Google Scholar 

  19. Pession A, Valsecchi MG, Masera G, et al. Long-term results of a randomized trial on extended use of high dose L-asparaginase for standard risk childhood acute lymphoblastic leukemia. Journal of clinical oncology: official journal of the American Society of Clinical Oncology. 2005;23:7161–7.

    Article  CAS  Google Scholar 

  20. Annino L, Vegna ML, Camera A, et al. Treatment of adult acute lymphoblastic leukemia (ALL): long-term follow-up of the GIMEMA ALL 0288 randomized study. Blood. 2002;99:863–71.

    Article  PubMed  CAS  Google Scholar 

  21. Gokbuget N, Hoelzer D. Novel antibody-based therapy for acute lymphoblastic leukaemia. Best Pract Res Clin Haematol. 2006;19:701–13.

    Article  PubMed  Google Scholar 

  22. Thomas DA, Faderl S, O'Brien S, et al. Chemoimmunotherapy with hyper-CVAD plus rituximab for the treatment of adult Burkitt and Burkitt-type lymphoma or acute lymphoblastic leukemia. Cancer. 2006;106:1569–80.

    Article  PubMed  CAS  Google Scholar 

  23. Gokbuget N, Hoelzer D. Treatment with monoclonal antibodies in acute lymphoblastic leukemia: current knowledge and future prospects. Ann Hematol. 2004;83:201–5.

    Article  PubMed  Google Scholar 

  24. •• Thomas DA, O'Brien S, Kantarjian HM. Monoclonal antibody therapy with rituximab for acute lymphoblastic leukemia. Hematol Oncol Clin North Am. 2009;23:949–971, v. Useful review highlighting improved outcomes and therapeutic benefit of adding rituximab to cytotoxic chemotherapy in patients with B-cell ALL.

    Article  PubMed  Google Scholar 

  25. Hoelzer D, Gokbuget N. Chemoimmunotherapy in acute lymphoblastic leukemia. Blood Rev. 2012;26:25–32.

    Article  PubMed  CAS  Google Scholar 

  26. Rizzieri DA, Johnson JL, Byrd JC, et al. Efficacy and toxicity of rituximab and brief duration, High intensity chemotherapy with filgrastim support for Burkitt or Burkitt - like leukemia/lymphoma: Cancer and Leukemia Group B (Calgb) Study 10002. Blood. 2010;116:374–5.

    Google Scholar 

  27. • Thomas DA, O'Brien S, Faderl S, et al. Chemoimmunotherapy with a modified hyper-CVAD and rituximab regimen improves outcome in de novo Philadelphia chromosome-negative precursor B-lineage acute lymphoblastic leukemia. Journal of clinical oncology: official journal of the American Society of Clinical Oncology. 2010;28:3880–9. One of the foremost adult B-cell ALL studies highlighting the efficacy and benefit of chemoimmunotherapy with rituximab over chemotherapy alone.

    Article  CAS  Google Scholar 

  28. Hoelzer D, Huettmann A, Kaul F, et al. Immunochemotherapy with rituximab Improves molecular CR rate and outcome in CD20+B-lineage standard and high risk patients; Results of 263 CD20+patients studied prospectively in GMALL study 07/2003. Blood. 2010;116:77–8.

    Google Scholar 

  29. Kantarjian H, Thomas D, Wayne AS, et al. Monoclonal antibody-based therapies: a new dawn in the treatment of acute lymphoblastic leukemia. Journal of clinical oncology: official journal of the American Society of Clinical Oncology. 2012;30:3876–83.

    Article  CAS  Google Scholar 

  30. FitzGerald DJ, Wayne AS, Kreitman RJ, et al. Treatment of hematologic malignancies with immunotoxins and antibody-drug conjugates. Cancer research. 2011;71:6300–9.

    Article  PubMed  CAS  Google Scholar 

  31. Maloney DG. Mechanism of action of rituximab. Anticancer Drugs. 2001;12 Suppl 2:S1–4.

    PubMed  CAS  Google Scholar 

  32. Ginaldi L, De Martinis M, Matutes E, et al. Levels of expression of CD19 and CD20 in chronic B cell leukaemias. J Clin Pathol. 1998;51:364–9.

    Article  PubMed  CAS  Google Scholar 

  33. Piccaluga PP, Arpinati M, Candoni A, et al. Surface antigens analysis reveals significant expression of candidate targets for immunotherapy in adult acute lymphoid leukemia. Leuk Lymphoma. 2011;52:325–7.

    Article  PubMed  Google Scholar 

  34. Raponi S, De Propris MS, Intoppa S, et al. Flow cytometric study of potential target antigens (CD19, CD20, CD22, CD33) for antibody-based immunotherapy in acute lymphoblastic leukemia: analysis of 552 cases. Leuk Lymphoma. 2011;52:1098–107.

    Article  PubMed  CAS  Google Scholar 

  35. Jazirehi AR, Vega MI, Bonavida B. Development of rituximab-resistant lymphoma clones with altered cell signaling and cross-resistance to chemotherapy. Cancer research. 2007;67:1270–81.

    Article  PubMed  CAS  Google Scholar 

  36. Thomas DA, O'Brien S, Jorgensen JL, et al. Prognostic significance of CD20 expression in adults with de novo precursor B-lineage acute lymphoblastic leukemia. Blood. 2009;113:6330–7.

    Article  PubMed  CAS  Google Scholar 

  37. Kantarjian HM, O'Brien S, Smith TL, et al. Results of treatment with hyper-CVAD, a dose-intensive regimen, in adult acute lymphocytic leukemia. Journal of clinical oncology: official journal of the American Society of Clinical Oncology. 2000;18:547–61.

    CAS  Google Scholar 

  38. Maury S, Huguet F, Leguay T, et al. Adverse prognostic significance of CD20 expression in adults with Philadelphia chromosome-negative B-cell precursor acute lymphoblastic leukemia. Haematologica. 2010;95:324–8.

    Article  PubMed  Google Scholar 

  39. Coiffier B, Lepage E, Briere J, et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med. 2002;346:235–42.

    Article  PubMed  CAS  Google Scholar 

  40. Robak T, Dmoszynska A, Solal-Celigny P, et al. Rituximab plus fludarabine and cyclophosphamide prolongs progression-free survival compared with fludarabine and cyclophosphamide alone in previously treated chronic lymphocytic leukemia. Journal of clinical oncology: official journal of the American Society of Clinical Oncology. 2010;28:1756–65.

    Article  CAS  Google Scholar 

  41. 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.

    Article  PubMed  CAS  Google Scholar 

  42. Dworzak MN, Gaipa G, Schumich A, et al. Modulation of antigen expression in B-cell precursor acute lymphoblastic leukemia during induction therapy is partly transient: evidence for a drug-induced regulatory phenomenon. Results of the AIEOP-BFM-ALL-FLOW-MRD-Study Group. Cytometry B Clin Cytom. 2010;78:147–53.

    PubMed  Google Scholar 

  43. Dworzak MN, Schumich A, Printz D, et al. CD20 up-regulation in pediatric B-cell precursor acute lymphoblastic leukemia during induction treatment: setting the stage for anti-CD20 directed immunotherapy. Blood. 2008;112:3982–8.

    Article  PubMed  CAS  Google Scholar 

  44. Watt TC, Park S, Cooper T. CD20 up-regulation in induction therapy for childhood B lymphoblastic leukemia. Blood. 2010;116:878–8.

    Article  Google Scholar 

  45. Gaipa G, Basso G, Maglia O, et al. Drug-induced immunophenotypic modulation in childhood ALL: implications for minimal residual disease detection. Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, UK. 2005;19:49–56.

    Article  CAS  Google Scholar 

  46. Salles G, Seymour JF, Offner F, et al. Rituximab maintenance for 2 years in patients with high tumour burden follicular lymphoma responding to rituximab plus chemotherapy (PRIMA): a phase 3, randomised controlled trial. Lancet. 2011;377:42–51.

    Article  PubMed  CAS  Google Scholar 

  47. Vidal L, Gafter-Gvili A, Salles G, et al. Rituximab maintenance for the treatment of patients with follicular lymphoma: an updated systematic review and meta-analysis of randomized trials. J Natl Cancer Inst. 2011;103:1799–806.

    Article  PubMed  CAS  Google Scholar 

  48. Cheson BD. Ofatumumab, a novel anti-CD20 monoclonal antibody for the treatment of B-cell malignancies. Journal of clinical oncology: official journal of the American Society of Clinical Oncology. 2010;28:3525–30.

    Article  CAS  Google Scholar 

  49. Wierda WG, Kipps TJ, Mayer J, et al. Ofatumumab as single-agent CD20 immunotherapy in fludarabine-refractory chronic lymphocytic leukemia. Journal of clinical oncology: official journal of the American Society of Clinical Oncology. 2010;28:1749–55.

    Article  CAS  Google Scholar 

  50. 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.

    PubMed  CAS  Google Scholar 

  51. Li B, Zhao L, Guo H, et al. Characterization of a rituximab variant with potent antitumor activity against rituximab-resistant B-cell lymphoma. Blood. 2009;114:5007–15.

    Article  PubMed  CAS  Google Scholar 

  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;104:1793–800.

    Article  PubMed  CAS  Google Scholar 

  53. Carnahan J, Wang P, Kendall R, et al. Epratuzumab, a humanized monoclonal antibody targeting CD22: characterization of in vitro properties. Clin Cancer Res. 2003;9:3982S–90S.

    PubMed  CAS  Google Scholar 

  54. Carnahan J, Stein R, Qu Z, et al. Epratuzumab, a CD22-targeting recombinant humanized antibody with a different mode of action from rituximab. Mol Immunol. 2007;44:1331–41.

    Article  PubMed  CAS  Google Scholar 

  55. Leonard JP, Coleman M, Ketas JC, et al. Phase I/II trial of epratuzumab (humanized anti-CD22 antibody) in indolent non-Hodgkin's lymphoma. Journal of clinical oncology: official journal of the American Society of Clinical Oncology. 2003;21:3051–9.

    Article  CAS  Google Scholar 

  56. Raetz EA, Cairo MS, Borowitz MJ, et al. Chemoimmunotherapy reinduction with epratuzumab in children with acute lymphoblastic leukemia in marrow relapse: a Children's Oncology Group Pilot Study. Journal of clinical oncology: official journal of the American Society of Clinical Oncology. 2008;26:3756–62.

    Article  CAS  Google Scholar 

  57. Raetz EA, Cairo MS, Borowitz MJ, et al. Reinduction chemoimmunotherapy with epratuzumab in relapsed acute lymphoblastic leukemia (ALL) in children, adolescents and young adults: Results from Children's Oncology Group (COG) Study ADVL04P2. Blood. 2011;118:264–4.

    Google Scholar 

  58. Treumann A, Lifely MR, Schneider P, et al. Primary structure of CD52. J Biol Chem. 1995;270:6088–99.

    Article  PubMed  CAS  Google Scholar 

  59. Gilleece MH, Dexter TM. Effect of Campath-1H antibody on human hematopoietic progenitors in vitro. Blood. 1993;82:807–12.

    PubMed  CAS  Google Scholar 

  60. Heit W, Bunjes D, Wiesneth M, 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. British journal of haematology. 1986;64:479–86.

    Article  PubMed  CAS  Google Scholar 

  61. Dyer MJ, Hale G, Hayhoe FG, et al. Effects of CAMPATH-1 antibodies in vivo in patients with lymphoid malignancies: influence of antibody isotype. Blood. 1989;73:1431–9.

    PubMed  CAS  Google Scholar 

  62. Rowan W, Tite J, Topley P, et al. 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;95:427–36.

    Article  PubMed  CAS  Google Scholar 

  63. Hillmen P, Skotnicki AB, Robak T, et al. Alemtuzumab compared with chlorambucil as first-line therapy for chronic lymphocytic leukemia. Journal of clinical oncology: official journal of the American Society of Clinical Oncology. 2007;25:5616–23.

    Article  CAS  Google Scholar 

  64. 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;99:3554–61.

    Article  PubMed  CAS  Google Scholar 

  65. Tibes R, Keating MJ, Ferrajoli A, et al. Activity of alemtuzumab in patients with CD52-positive acute leukemia. Cancer. 2006;106:2645–51.

    Article  PubMed  CAS  Google Scholar 

  66. Angiolillo AL, Yu AL, Reaman G, et al. A phase II study of Campath-1H in children with relapsed or refractory acute lymphoblastic leukemia: a Children's Oncology Group report. Pediatr Blood Cancer. 2009;53:978–83.

    Article  PubMed  Google Scholar 

  67. Stock W, Sanford B, Lozanski G, et al. Alemtuzumab can be incorporated into front-line therapy of adult acute lymphoblastic leukemia (ALL): Final phase I results of a Cancer and Leukemia Group B study (CALGB 10102). Blood. 2009;114:345–5.

    Google Scholar 

  68. Cruz RI, Hernandez-Ilizaliturri FJ, Olejniczak S, et al. CD52 over-expression affects rituximab-associated complement-mediated cytotoxicity but not antibody-dependent cellular cytotoxicity: preclinical evidence that targeting CD52 with alemtuzumab may reverse acquired resistance to rituximab in non-Hodgkin lymphoma. Leuk Lymphoma. 2007;48:2424–36.

    Article  PubMed  CAS  Google Scholar 

  69. Ricart AD. Antibody-drug conjugates of calicheamicin derivative: gemtuzumab ozogamicin and inotuzumab ozogamicin. Clin Cancer Res. 2011;17:6417–27.

    Article  PubMed  CAS  Google Scholar 

  70. Goy A, Leach J, Ehmann C, et al. Inotuzumab Ozogamicin (CMC-544) in patients with indolent B-cell NHL that is refractory to rituximab alone, rituximab and chemotherapy, or radioimmunotherapy: preliminary safety and efficacy from a phase 2 trial. Blood. 2010;116:192–3.

    Google Scholar 

  71. Advani A, Coiffier B, Czuczman MS, et al. Safety, pharmacokinetics, and preliminary clinical activity of inotuzumab ozogamicin, a novel immunoconjugate for the treatment of B-cell non-Hodgkin's lymphoma: results of a phase I study. Journal of clinical oncology: official journal of the American Society of Clinical Oncology. 2010;28:2085–93.

    Article  CAS  Google Scholar 

  72. Fayad L, Patel H, Verhoef G, et al. Safety and clinical activity of the anti-CD22 immunoconjugate inotuzumab ozogamicin (CMC-544) in combination with rituximab in follicular lymphoma or diffuse large B-Cell lymphoma: Preliminary report of a phase 1/2 study. Blood. 2008;112:105–5.

    Google Scholar 

  73. •• Kantarjian H, Thomas D, Jorgensen J, et al. Inotuzumab ozogamicin, an anti-CD22-calecheamicin conjugate, for refractory and relapsed acute lymphocytic leukaemia: a phase 2 study. Lancet Oncol. 2012;13:403–11. Article highlighting the efficacy of novel anti-CD22 antibody Inotuzumab ozogamicin in patients with relapsed/refractory B-cell ALL.

    Article  PubMed  CAS  Google Scholar 

  74. Blanc V, Bousseau A, Caron A, et al. SAR3419: an anti-CD19-Maytansinoid immunoconjugate for the treatment of B-cell malignancies. Clin Cancer Res. 2011;17:6448–58.

    Article  PubMed  CAS  Google Scholar 

  75. Al-Katib AM, Aboukameel A, Mohammad R, et al. Superior antitumor activity of SAR3419 to rituximab in xenograft models for non-Hodgkin's lymphoma. Clin Cancer Res. 2009;15:4038–45.

    Article  PubMed  CAS  Google Scholar 

  76. Younes A, Gordon L, Kim S, et al. Phase I multi-dose escalation study of the anti-CD19 maytansinoid immunoconjugate SAR3419 administered by intravenous (IV) Infusion every 3 weeks to patients with relapsed refractory B-Cell non-hodgkin's lymphoma (NHL). Blood. 2009;114:243–3.

    Google Scholar 

  77. Polson AG, Ho WY, Ramakrishnan V. Investigational antibody-drug conjugates for hematological malignancies. Expert Opin Inv Drug. 2011;20:75–85.

    Article  CAS  Google Scholar 

  78. Kreitman RJ, Pastan I. Antibody fusion proteins: anti-CD22 recombinant immunotoxin moxetumomab pasudotox. Clin Cancer Res. 2011;17:6398–405.

    Article  PubMed  CAS  Google Scholar 

  79. Kreitman RJ, Squires DR, Stetler-Stevenson M, et al. Phase I trial of recombinant immunotoxin RFB4(dsFv)-PE38 (BL22) in patients with B-cell malignancies. Journal of clinical oncology: official journal of the American Society of Clinical Oncology. 2005;23:6719–29.

    Article  CAS  Google Scholar 

  80. Kreitman RJ, Wilson WH, Bergeron K, et al. Efficacy of the anti-CD22 recombinant immunotoxin BL22 in chemotherapy-resistant hairy-cell leukemia. N Engl J Med. 2001;345:241–7.

    Article  PubMed  CAS  Google Scholar 

  81. Kreitman RJ, Stetler-Stevenson M, Margulies I, et al. Phase II trial of recombinant immunotoxin RFB4(dsFv)-PE38 (BL22) in patients with hairy cell leukemia. Journal of clinical oncology: official journal of the American Society of Clinical Oncology. 2009;27:2983–90.

    Article  CAS  Google Scholar 

  82. Wayne AS, Kreitman RJ, Findley HW, et al. Anti-CD22 immunotoxin RFB4(dsFv)-PE38 (BL22) for CD22-positive hematologic malignancies of childhood: preclinical studies and phase I clinical trial. Clin Cancer Res. 2010;16:1894–903.

    Article  PubMed  CAS  Google Scholar 

  83. Salvatore G, Beers R, Margulies I, et al. Improved cytotoxic activity toward cell lines and fresh leukemia cells of a mutant anti-CD22 immunotoxin obtained by antibody phage display. Clin Cancer Res. 2002;8:995–1002.

    PubMed  CAS  Google Scholar 

  84. Kreitman RJ, Tallman MS, Coutre S, et al. A phase 1 study of moxetumomab pasudotox, an anti-CD22 recombinant immunotoxin, in relapsed/refractory hairy cell leukemia (HCL): Updated results. Blood. 2010;116:1042–3.

    Google Scholar 

  85. • Wayne AS, Bhojwani D, Silverman LB, et al. A novel anti-CD22 immunotoxin, moxetumomab pasudotox: Phase I study in pediatric acute lymphoblastic leukemia (ALL). Blood. 2011;118:113–3. One of the first phase II studies to evaluate the efficacy and tolerability of conjugated immunotoxons in B-cell ALL.

    Google Scholar 

  86. Weldon JE, Xiang L, Chertov O, et al. A protease-resistant immunotoxin against CD22 with greatly increased activity against CLL and diminished animal toxicity. Blood. 2009;113:3792–800.

    Article  PubMed  CAS  Google Scholar 

  87. Onda M, Beers R, Xiang LM, et al. Recombinant immunotoxin against B-cell malignancies with no immunogenicity in mice by removal of B-cell epitopes. Proceedings of the National Academy of Sciences of the United States of America. 2011;108:5742–7.

    Article  PubMed  CAS  Google Scholar 

  88. Bargou R, Leo E, Zugmaier G, et al. Tumor regression in cancer patients by very low doses of a T cell-engaging antibody. Science. 2008;321:974–7.

    Article  PubMed  CAS  Google Scholar 

  89. Topp MS, Goekbuget N, Kufer P, et al. Blinatumomab (anti-Cd19 Bite?) for targeted therapy of minimal residual disease (Mrd) in Patients with B precursor acute lymphoblastic leukemia (All): Update of an ongoing Phase II study. Haematol-Hematol J. 2009;94:195–5.

    Article  Google Scholar 

  90. Topp MS, Gokbuget N, Zugmaier G, et al.: Long-term follow-up of hematological relapse-free survival in a phase 2 study of blinatumomab in patients with minimal residual disease (MRD) of B-precursor acute lymphoblastic leukemia (ALL). Blood. 2012;Epub 2012/10/02: ISSN 1528-0020 (Electronic)

  91. Handgretinger R, Zugmaier G, Henze G, et al. Complete remission after blinatumomab-induced donor T-cell activation in three pediatric patients with post-transplant relapsed acute lymphoblastic leukemia. Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, UK. 2011;25:181–4.

    Article  CAS  Google Scholar 

  92. Topp MS, Goekbuget N, Zugmaier G, et al. Anti-CD19 BITE Blinatumomab induces high complete remission rate In adult patients with relapsed B-precursor ALL: Updated results of an ongoing phase II trial. Blood. 2011;118:115–5.

    Google Scholar 

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Naval Daver declares that he has no conflict of interest.

Susan O’Brien declares that she has no conflict of interest.

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  1. Department of Leukemia, University of Texas M D Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 0428, Houston, TX, 77030, USA

    Naval Daver & Susan O’Brien

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Daver, N., O’Brien, S. Novel Therapeutic Strategies in Adult Acute Lymphoblastic Leukemia – A Focus on Emerging Monoclonal Antibodies. Curr Hematol Malig Rep 8, 123–131 (2013). https://doi.org/10.1007/s11899-013-0160-7

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