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Antibody Therapy for Acute Lymphoblastic Leukemia

  • Acute Lymphocytic Leukemia (F Ravandi, Section Editor)
  • Published:
Current Hematologic Malignancy Reports Aims and scope Submit manuscript

Abstract

Advances in chemotherapy administration have made acute lymphoblastic leukemia (ALL) a curable disease; however, most patients will relapse, despite readily attaining a complete remission. Treatment of relapse has shown dismal results with little advances made in the recent decades. Antigenic-directed therapy of ALL can complement cytotoxic chemotherapy and has shown encouraging results. This review will evaluate four antigens in ALL (CD20, CD22, CD52, and CD19) and therapeutic strategies to target them. We will review the clinical and preclinical data surrounding rituximab, epratuzumab, inotuzumab ozogamicin, alemtuzumab, blinatumomab, and chimeric antigen receptor-modified T-cell therapy.

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References

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

  1. 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 

  2. Fielding AK, Richards SM, Chopra R, et al. Outcome of 609 adults after relapse of acute lymphoblastic leukemia (ALL); an MRC UKALL12/ECOG 2993 study. Blood. 2007;109:944–50.

    Article  PubMed  CAS  Google Scholar 

  3. Paietta E, Li X, Richards S, et al. Implications for the use of monoclonal antibodies in future adult ALL trials: analysis of antigen expression in 505 B-Lineage (B-Lin) all patients (pts) on the MRC UKALLXII/ECOG2993 intergroup trial [abstract]. Proc ASH. 2008;112:1907. http://bloodjournal.hematologylibrary.org.

    Google Scholar 

  4. • 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. Lists clinical characteristics of CD19, CD20, CD22, and CD33 expression in ALL.

    Article  PubMed  CAS  Google Scholar 

  5. • 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. CD20 expression denotes a poor prognosis in precursor B-ALL.

    Article  PubMed  CAS  Google Scholar 

  6. Borowitz MJ, Shuster J, Carroll AJ, et al. Prognostic significance of fluorescence intensity of surface marker expression in childhood B-precursor acute lymphoblastic leukemia. A pediatric oncology group study. Blood. 1997;89:3960–6.

    PubMed  CAS  Google Scholar 

  7. 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 

  8. • 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. J Clin Oncol. 2010;28:3880–9. Rituximab use with HyperCVAD during induction alleviates the adverse prognosis of CD20 expression in Philadelphia chromosome negative B-ALL.

    Article  PubMed  CAS  Google Scholar 

  9. 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. [abstract]. Proc ASH. 2010;116:170. http://bloodjournal.hematologylibrary.org.

    Google Scholar 

  10. Brüggemann M, Raff T, Flohr T, et al. Clinical significance of minimal residual disease quantification in adult patients with standard-risk acute lymphoblastic leukemia. Blood. 2006;107:1116–23.

    Article  PubMed  Google Scholar 

  11. Poe JC, Fujimoto Y, Hasegawa M, et al. CD22 regulates B lymphocyte function in vivo through both ligand-dependent and ligand-independent mechanisms. Nat Immunol. 2004;5:1078–87.

    Article  PubMed  CAS  Google Scholar 

  12. Leonard JP, Schuster SJ, Emmanouilides C, et al. Durable complete responses from therapy with combined epratuzumab and rituximab: final results from an international multicenter, phase 2 study in recurrent, indolent, non-Hodgkin lymphoma. Cancer. 2008;113:2714–23.

    Article  PubMed  CAS  Google Scholar 

  13. Leonard JP, Coleman M, Ketas JC, et al. Epratuzumab, a humanized anti-CD22 antibody, in aggressive non-Hodgkin’s lymphoma: phase I/II clinical trial results. Clin Cancer Res. 2004;10:5327–34.

    Article  PubMed  CAS  Google Scholar 

  14. • 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. J Clin Oncol. 2008;26:3756–62. Early study with epratuzumab in childhood ALL showing limited toxicity and early promise.

    Article  PubMed  CAS  Google Scholar 

  15. Raetz EA, Borowitz MJ, Devidas M, et al. Reinduction platform for children with first marrow relapse of acute lymphoblastic leukemia: a children’s oncology group study[corrected]. J Clin Oncol. 2008;26:3971–8.

    Article  PubMed  CAS  Google Scholar 

  16. 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 [abstract]. Proc ASH. 2011;118:573. http://bloodjournal.hematologylibrary.org.

    Google Scholar 

  17. de Vries JF, Zwaan CM, De Bie M, et al. The novel calicheamicin-conjugated CD22 antibody inotuzumab ozogamicin (CMC-544) effectively kills primary pediatric acute lymphoblastic leukemia cells. Leukemia. 2011; In press.

  18. Dijoseph JF, Dougher MM, Armellino DC, Evans DY, Damle NK. Therapeutic potential of CD22-specific antibody-targeted chemotherapy using inotuzumab ozogamicin (CMC-544) for the treatment of acute lymphoblastic leukemia. Leukemia. 2007;21:2240–5.

    Article  PubMed  CAS  Google Scholar 

  19. • 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. J Clin Oncol. 2010;28:2085–93. IO use in relapsed and refractory NHL had limited toxicity with 68 % ORR in follicular lymphoma.

    Article  PubMed  CAS  Google Scholar 

  20. Jabbour E, O’Brien S, Thomas D, et al. Inotuzumab ozogamicin (IO; CMC544), a CD22 monoclonal antibody attached to calicheamycin, produces complete response (CR) plus complete marrow response (mCR) of greater than 50 % in refractory relapse (R-R) acute lymphocytic leukemia (ALL) [abstract]. Proc ASCO. 2011;29:6507. http://www.asco.org.

    Google Scholar 

  21. Watanabe T, Masuyama J-I, Sohma Y, et al. CD52 is a novel costimulatory molecule for induction of CD4+ regulatory T cells. Clin Immunol. 2006;120:247–59.

    Article  PubMed  CAS  Google Scholar 

  22. 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 

  23. Hu Y, Turner MJ, Shields J, et al. Investigation of the mechanism of action of alemtuzumab in a human CD52 transgenic mouse model. Immunology. 2009;128:260–70.

    Article  PubMed  CAS  Google Scholar 

  24. 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 Canc. 2009;53:978–83.

    Article  Google Scholar 

  25. 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) [abstract]. Proc ASH. 2009;114:838.

    Google Scholar 

  26. Scheuermann RH, Racila E. CD19 antigen in leukemia and lymphoma diagnosis and immunotherapy. Leuk Lymphoma. 1995;18:385–97.

    Article  PubMed  CAS  Google Scholar 

  27. Nagorsen D, Baeuerle PA. Immunomodulatory therapy of cancer with T cell-engaging BiTE antibody blinatumomab. Exp Cell Res. 2011;317:1255–60.

    Article  PubMed  CAS  Google Scholar 

  28. Nagorsen D, Bargou R, Ruttinger D, et al. Immunotherapy of lymphoma and leukemia with T-cell engaging BiTE antibody blinatumomab. Leuk Lymphoma. 2009;50:886–91.

    Article  PubMed  CAS  Google Scholar 

  29. Brischwein K, Parr L, Pflanz S, et al. Strictly target cell-dependent activation of T cells by bispecific single-chain antibody constructs of the BiTE class. J Immunother. 2007;30:798–807.

    Article  PubMed  CAS  Google Scholar 

  30. 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 

  31. • Topp MS, Kufer P, Gökbuget N, et al. Targeted therapy with the T-cell-engaging antibody blinatumomab of chemotherapy-refractory minimal residual disease in B-lineage acute lymphoblastic leukemia patients results in high response rate and prolonged leukemia-free survival. J Clin Oncol. 2011;29:2493–8. Blinatumomab is well tolerated and efficacious in MRD-positive B-ALL.

    Article  PubMed  CAS  Google Scholar 

  32. 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. 2011;25:181–4.

    Article  PubMed  CAS  Google Scholar 

  33. • Porter DL, Levine BL, Kalos M, Bagg A, June CH. Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia. N Engl J Med. 2011;365:725–33. First description of CAR therapy in CLL.

    Article  PubMed  CAS  Google Scholar 

  34. Kalos M, Levine BL, Porter DL, et al. T cells with chimeric antigen receptors have potent antitumor effects and can establish memory in patients with advanced leukemia. Sci Transl Med. 2011;3:95ra73.

    Article  PubMed  CAS  Google Scholar 

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Disclosure

C. A. Portell: none; A. S. Advani: consultant to Pfizer.

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Correspondence to Anjali S. Advani.

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Portell, C.A., Advani, A.S. Antibody Therapy for Acute Lymphoblastic Leukemia. Curr Hematol Malig Rep 7, 153–159 (2012). https://doi.org/10.1007/s11899-012-0120-7

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