Vol 7, No 4 (2016)
Review paper
Published online: 2017-04-07

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Blinatumomab — a novel drug in patients with relapsed/refractory acute lymphoblastic leukemia

Joanna Sawczuk-Chabin, Anna Ejduk, Ewa Lech-Marańda
Hematologia 2016;7(4):312-326.


The long term prognosis of adult patients with relapsed/refractory (R/R) acute lymphoblastic leu­kemia (ALL) is poor. There is no standard treatment for relapsed ALL and reinduction therapy should only be a “bridge treatment” in allogeneic hematopoietic stem cell transplantation (allo- -HSCT). In spite of obtaining an initial response to treatment, the duration of response using standard chemotherapy is usually short and the next relapses are chemoresistant. Immunotherapy with monoclonal antibodies as a targeted therapy represents a novel approach for treating patients with R/R ALL. The objective of immunotherapy is to improve the relapse-free and overall survival without increasing the toxicity of treatment. In this review, the mechanism of action and clini­cal efficacy of the novel bispecific antibody blinatumomab is discussed. The European Medicines Agency approved blinatumomab in 2015 for treating adult patients with Philadelphia chromosome negative R/R B-ALL.

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  1. Fielding AK, Richards SM, Chopra R, et al. Medical Research Council of the United Kingdom Adult ALL Working Party, Eastern Cooperative Oncology Group. Outcome of 609 adults after relapse of acute lymphoblastic leukemia (ALL); an MRC UKALL12/ECOG 2993 study. Blood. 2007; 109(3): 944–950.
  2. Oriol A, Vives S, Hernández-Rivas JM, et al. Programa Español de Tratamiento en Hematologia Group. Outcome after relapse of acute lymphoblastic leukemia in adult patients included in four consecutive risk-adapted trials by the PETHEMA Study Group. Haematologica. 2010; 95(4): 589–596.
  3. Terwey TH, Massenkeil G, Tamm I, et al. Allogeneic SCT in refractory or relapsed adult ALL is effective without prior reinduction chemotherapy. Bone Marrow Transplant. 2008; 42(12): 791–798.
  4. Frey NV, Luger SM. How I treat adults with relapsed or refractory Philadelphia chromosome-negative acute lymphoblastic leukemia. Blood. 2015; 126(5): 589–596.
  5. Cornelissen JJ, Carston M, Kollman C, et al. Unrelated marrow transplantation for adult patients with poor-risk acute lymphoblastic leukemia: strong graft-versus-leukemia effect and risk factors determining outcome. Blood. 2001; 97(6): 1572–1577.
  6. Faderl S, Thomas DA, O'Brien S, et al. Augmented hyper-CVAD based on dose-intensified vincristine, dexamethasone, and asparaginase in adult acute lymphoblastic leukemia salvage therapy. Clin Lymphoma Myeloma Leuk. 2011; 11(1): 54–59.
  7. Camera A, Annino L, Chiurazzi F, et al. GIMEMA ALL - Rescue 97: a salvage strategy for primary refractory or relapsed adult acute lymphoblastic leukemia. Haematologica. 2004; 89(2): 145–153.
  8. Weiss MA, Aliff TB, Tallman MS, et al. A single, high dose of idarubicin combined with cytarabine as induction therapy for adult patients with recurrent or refractory acute lymphoblastic leukemia. Cancer. 2002; 95(3): 581–587.
  9. Montillo M, Tedeschi A, Centurioni R, et al. Treatment of relapsed adult acute lymphoblastic leukemia with fludarabine and cytosine arabinoside followed by granulocyte colony-stimulating factor (FLAG-GCSF). Leuk Lymphoma. 1997; 25(5-6): 579–583.
  10. Faderl S, Balakrishnan K, Thomas DA, et al. Phase 2 clinical and pharmacologic study of clofarabine in patients with refractory or relapsed acute leukemia. Blood. 2003; 102(7): 2379–2386.
  11. Barba P, Sampol A, Calbacho M, et al. Clofarabine-based chemotherapy for relapsed/refractory adult acute lymphoblastic leukemia and lymphoblastic lymphoma. The Spanish experience. Am J Hematol. 2012; 87(6): 631–634.
  12. Schiller G, Lee M, Territo M, et al. Phase II study of etoposide, ifosfamide, and mitoxantrone for the treatment of resistant adult acute lymphoblastic leukemia. Am J Hematol. 1993; 43(3): 195–199.
  13. Giebel S, Krawczyk-Kulis M, Adamczyk-Cioch M, et al. Polish Adult Leukemia Group. Fludarabine, cytarabine, and mitoxantrone (FLAM) for the treatment of relapsed and refractory adult acute lymphoblastic leukemia. A phase study by the Polish Adult Leukemia Group (PALG). Ann Hematol. 2006; 85(10): 717–722.
  14. Yavuz S, Paydas S, Disel U, et al. IDA-FLAG regimen for the therapy of primary refractory and relapse acute leukemia: a single-center experience. Am J Ther. 2006; 13(5): 389–393.
  15. Aldoss I, Pullarkat V, Patel R, et al. An effective reinduction regimen for first relapse of adult acute lymphoblastic leukemia. Med Oncol. 2013; 30(4): 744.
  16. Martino R, Bellido M, Brunet S, et al. Intensive salvage chemotherapy for primary refractory or first relapsed adult acute lymphoblastic leukemia: results of a prospective trial. Haematologica. 1999; 84: 505–510.
  17. Abbi KKS, Rybka W, Ehmann WC, et al. Phase I/II study of clofarabine, etoposide, and mitoxantrone in patients with refractory or relapsed acute leukemia. Clin Lymphoma Myeloma Leuk. 2015; 15(1): 41–46.
  18. Advani AS, Gundacker HM, Sala-Torra O, et al. Southwest Oncology Group Study S0530: a phase 2 trial of clofarabine and cytarabine for relapsed or refractory acute lymphocytic leukaemia. Br J Haematol. 2010; 151(5): 430–434.
  19. O'Brien S, Schiller G, Lister J, et al. High-dose vincristine sulfate liposome injection for advanced, relapsed, and refractory adult Philadelphia chromosome-negative acute lymphoblastic leukemia. J Clin Oncol. 2013; 31(6): 676–683.
  20. Silverman JA, Reynolds L, Deitcher SR. Pharmacokinetics and pharmacodynamics of vincristine sulfate liposome injection (VSLI) in adults with acute lymphoblastic leukemia. J Clin Pharmacol. 2013; 53(11): 1139–1145.
  21. Berg SL, Blaney SM, Devidas M, et al. Children's Oncology Group. Phase II study of nelarabine (compound 506U78) in children and young adults with refractory T-cell malignancies: a report from the Children's Oncology Group. J Clin Oncol. 2005; 23(15): 3376–3382.
  22. DeAngelo DJ, Yu D, Johnson JL, et al. Nelarabine induces complete remissions in adults with relapsed or refractory T-lineage acute lymphoblastic leukemia or lymphoblastic lymphoma: Cancer and Leukemia Group B study 19801. Blood. 2007; 109(12): 5136–5142.
  23. Thomas D, 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(7): 1569–1580.
  24. Hoelzer D, Gökbuget N. Chemoimmunotherapy in acute lymphoblastic leukemia. Blood Rev. 2012; 26(1): 25–32.
  25. Jabbour E, Kantarajian H, Thomas D, et al. Phase II study of the hyper-CVAD regimen in combination with ofatumumab as frontline therapy for adults with Cd-20 positive acute lymphoblastic leukemia. Blood. 2013; 122: 2664.
  26. Sharkey RM, Govindan SV, Cardillo TM, et al. Epratuzumab-SN-38: a new antibody-drug conjugate for the therapy of hematologic malignancies. Mol Cancer Ther. 2012; 11(1): 224–234.
  27. Advani AS, McDonough S, Coutre S, et al. SWOG S0910: a phase 2 trial of clofarabine/cytarabine/epratuzumab for relapsed/refractory acute lymphocytic leukaemia. Br J Haematol. 2014; 165(4): 504–509.
  28. Kantarjian HM, DeAngelo DJ, Stelljes M, et al. Inotuzumab Ozogamicin versus Standard Therapy for Acute Lymphoblastic Leukemia. N Engl J Med. 2016; 375(8): 740–753.
  29. Wu J, Fu J, Zhang M, et al. Blinatumomab: a bispecific T cell engager (BiTE) antibody against CD19/CD3 for refractory acute lymphoid leukemia. J Hematol Oncol. 2015; 8: 104.
  30. Charakterystyka Produktu Leczniczego. Aneks 1: Blincyto. https://ec.europa.eu/health/documents/community-register/.../anx_133349_pl.pdf (04.03.2016).
  31. Kantarjian H, Stein A, Gökbuget N, et al. Blinatumomab versus Chemotherapy for Advanced Acute Lymphoblastic Leukemia. N Engl J Med. 2017; 376(9): 836–847.
  32. Nagorsen D, Kufer P, Baeuerle PA, et al. Blinatumomab: a historical perspective. Pharmacol Ther. 2012; 136(3): 334–342.
  33. Goebeler M, Viardot A, Noppeney R, et al. Blinatumomab (CD3/CD19 Bite antybody) results in high response rate in patients with relapsed non-Hodgkin lymphoma (NHL) including MCL and DLBCL. Ann Oncol. 2011; 22(supl. 4): 104–105.
  34. 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(18): 2493–2498.
  35. Topp MS, Gökbuget N, Zugmaier G, et al. Long-term follow-up of hematologic relapse-free survival in a phase 2 study of blinatumomab in patients with MRD in B-lineage ALL. Blood. 2012; 120(26): 5185–5187.
  36. Gökbuget N, Dombret H, Bonifacio M, et al. BLAST: a confirmatory, single arm, phase 2 study of Blinatumomab, a bispecific T-cell engager (BiTE) antibody constructor, in patients with minimal residual disease B — precursor acute lymphoblastic leukemia (ALL). Blood. 2014; 123: abstrakt 379.
  37. Kantarjian HM, Stein AS, Bargou RC, et al. Phase II trial of the anti-CD19 bispecific T cell-engager blinatumomab shows hematologic and molecular remissions in patients with relapsed or refractory B-precursor acute lymphoblastic leukemia. J Clin Oncol. 2014; 32(36): 4134–4140.
  38. Zugmaier G, Gökbuget N, Klinger M, et al. Long-term survival and T-cell kinetics in relapsed/refractory ALL patients who achieved MRD response after blinatumomab treatment. Blood. 2015; 126(24): 2578–2584.
  39. Topp M, Gökbuget N, Stein A, et al. Safety and activity of blinatumomab for adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia: a multicentre, single-arm, phase 2 study. The Lancet Oncology. 2015; 16(1): 57–66.
  40. Stein A, Topp M, Gokbuget N, et al. Outcomes of Hematopoietic Stem Cell Transplantation (HSCT) Among Adults with Relapsed/Refractory (r/r) Acute Lymphoblastic Leukemia (ALL) Achieving Remission with Blinatumomab. Biology of Blood and Marrow Transplantation. 2016; 22(3): S35–S36.
  41. Stein A.S. Treatment with anti-CD19 BiTE ® blinatumomab in adult patients with relapsed/refractory B-precursor acute lymphoblastic leukemia (r/r ALL) post allogeneic hematopoietic stem cell transplantation. EBMT Annual Meeting 2016, Bone Marrow Transplantation Abstract Book 2016, abstrakt O015. 2016.
  42. Blinatumomab improved overall survival in patients with relapse or refractory Philadelphia negative B-cell precursor acute lymphoblastic leukemia in a randomized, open-label phase 3 study (TOWER). 2016.

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