Vol 9, No 4 (2018)
Review paper
Published online: 2019-03-06

open access

Page views 1344
Article views/downloads 1384
Get Citation

Connect on Social Media

Connect on Social Media

Inotuzumab ozogamycin in the treatment of patients with acute lymphoblastic leukemia

Aleksandra Gołos1, Joanna Góra-Tybor1
Hematologia 2018;9(4):297-305.

Abstract

Acute lymphoblastic leukemia (ALL) comprises about 20% of leukemias in adult. Though the high complete remission (CR) rates after the first-line chemotherapy, only 30–40% of ALL patients may be cured. The prognosis of relapsed/refractory ALL remains poor. The 5-year overall survival (OS) rate is 7–10%. In recent years, new therapies utilizing monoclonal antibodies have been investigated. Inotuzumab ozogamycin is a humanized anti-CD22 antibody conjugated to an alkylating agent — calicheamicin. The drug was registered for relapsed/refractory ALL in adults based on INO-VATE trial, a phase III trial comparing efficacy of inotuzumab ozogamycin to chemotherapy. CR rates, progression-free survival, and OS were significantly higher in the inotuzumab group. In addition, significantly more patients from the inotuzumab group were treated with allogeneic hematopoietic stem cell transplantation (allo-HSCT). The most common adverse events were neutropenia and thrombocytopenia. Among the non-hematological adverse events the veno-occlusive disease (VOD) was the most dangerous. The frequency of VOD increased in patients who underwent allo-HSCT. This article presents the most important clinical trials with inotuzumab ozogamycin and the toxicity of the drug.

Article available in PDF format

View PDF (Polish) Download PDF file

References

  1. Seferyńska I. Zachorowania na ostre białaczki szpikowe i limfoblastyczne u dorosłych w Polsce w latach 2004–2010. Hematologia. 2015; 6(B): 1–40.
  2. Inaba H, Greaves M, Mullighan CG. Acute lymphoblastic leukaemia. Lancet. 2013; 381(9881): 1943–1955.
  3. 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.
  4. Maury S, Chevret S, Thomas X, et al. for GRAALL. Rituximab in B-lineage adult acute lymphoblastic leukemia. N Engl J Med. 2016; 375(11): 1044–1053.
  5. Sawczuk-Chabin J, Ejduk A, Lech-Marańda E. Blinatumomab — nowy lek u chorych na nawrotową/ /oporną ostrą białaczkę limfoblastyczną. Hematologia. 2017; 7(4): 312–326.
  6. 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.
  7. 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.
  8. Brentjens RJ, Rivière I, Park JH, et al. Safety and persistence of adoptively transferred autologous CD19-targeted T cells in patients with relapsed or chemotherapy refractory B-cell leukemias. Blood. 2011; 118(18): 4817–4828.
  9. Brudno JN, Somerville RPT, Shi V, et al. Allogeneic T cells that express an anti-CD19 chimeric antigen receptor induce remissions of B-cell malignancies that progress after allogeneic hematopoietic stem-cell transplantation without causing graft-versus-host disease. J Clin Oncol. 2016; 34(10): 1112–1121.
  10. Park JH, Rivière I, Gonen M, et al. Long-term follow-up of CD19 CAR therapy in acute lymphoblastic leukemia. N Engl J Med. 2018; 378(5): 449–459.
  11. Gardner RA, Finney O, Annesley C, et al. Intent-to-treat leukemia remission by CD19 CAR T cells of defined formulation and dose in children and young adults. Blood. 2017; 129(25): 3322–3331.
  12. Agency. Kymirah EM. https://www.ema.europa.eu/en/medicines/human/EPAR/kymriah (21 Dec 2018).
  13. Haso W, Lee DW, Shah NN, et al. Anti-CD22-chimeric antigen receptors targeting B-cell precursor acute lymphoblastic leukemia. Blood. 2013; 121(7): 1165–1174.
  14. FDA. Besponsa U. (inotuzumab ozogamicin) for injection, for inntravenous use: US prescribing information. 2017. https://www.fda.gov/ (17 Oct 2018).
  15. Agency. Besponsa EM. (inotuzumab ozogamicin): EU summary of product characteristics. 2017. https://www.ema.europa.eu/ (17 Oct 2018).
  16. Besponsa. Charakterystyka produktu leczniczego 2017. https://ec.europa.eu/health/documents/community-register/2017/20170629138094/anx_138094_pl.pdf (17 Oct 2018).
  17. Moyron-Quiroz JE, Partida-Sánchez S, Donís-Hernández R, et al. Expression and function of CD22, a B-cell restricted molecule. Scand J Immunol. 2002; 55(4): 343–351.
  18. Hinman LM, Hamann PR, Wallace R, et al. Preparation and characterization of monoclonal antibody conjugates of the calicheamicins: a novel and potent family of antitumor antibiotics. Cancer Res. 1993; 53(14): 3336–3342.
  19. DiJoseph JF, Armellino DC, Boghaert ER, et al. Antibody-targeted chemotherapy with CMC-544: a CD22-targeted immunoconjugate of calicheamicin for the treatment of B-lymphoid malignancies. Blood. 2004; 103(5): 1807–1814.
  20. Shor B, Gerber HP, Sapra P. Preclinical and clinical development of inotuzumab-ozogamicin in hematological malignancies. Mol Immunol. 2015; 67(2 Pt A): 107–116.
  21. 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. 2012; 26(2): 255–264.
  22. Thota S, Advani A. Inotuzumab ozogamicin in relapsed B-cell acute lymphoblastic leukemia. Eur J Haematol. 2017; 98(5): 425–434.
  23. 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(12): 2085–2093.
  24. DeAngelo DJ, Stock W, Stein AS, et al. Inotuzumab ozogamicin in adults with relapsed or refractory CD22-positive acute lymphoblastic leukemia: a phase 1/2 study. Blood Adv. 2017; 1(15): 1167–1180.
  25. 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(4): 403–411.
  26. Kantarjian H, Thomas D, Jorgensen J, et al. Results of inotuzumab ozogamicin, a CD22 monoclonal antibody, in refractory and relapsed acute lymphocytic leukemia. Cancer. 2013; 119(15): 2728–2736.
  27. Advani AS, Stein AS, Kantarjian HM, et al. et al.. A phase II study of weekly inotuzumab ozogamicin (InO) in adult patients with CD22-positive acute lymphoblastic leukemia (ALL) in second or later salvage. Blood. 2014; 124(21): 2255–2255.
  28. Jabbour E, Ravandi F, Kebriaei P, et al. Salvage chemoimmunotherapy with inotuzumab ozogamicin combined with mini-hyper-CVD for patients with relapsed or refractory Philadelphia chromosome-negative acute lymphoblastic leukemia: a phase 2 clinical trial. JAMA Oncol. 2018; 4(2): 230–234.
  29. Kantarjian H, Ravandi F, Short N, et al. Inotuzumab ozogamicin in combination with low-intensity chemotherapy for older patients with Philadelphia chromosome-negative acute lymphoblastic leukaemia: a single-arm, phase 2 study. Lancet Oncol. 2018; 19(2): 240–248.
  30. 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.
  31. Jabbour EJ, DeAngelo DJ, Stelljes M, et al. Efficacy and safety analysis by age cohort of inotuzumab ozogamicin in patients with relapsed or refractory acute lymphoblastic leukemia enrolled in INO-VATE. Cancer. 2018; 124(8): 1722–1732.
  32. Oostrum Iv, Su Y, Heeg B, et al. Quality-adjusted life years (QALY) for inotuzumab ozogamicin vs standard of care for relapsed/refractory acute lymphoblastic leukemia (R/R ALL). J Clin Oncol. 2017; 35(15 Suppl): e18506–e18506.
  33. Assi R, Kantarjian H, Ravandi F, et al. Inotuzumab ozogamicin (IO) combined with mini-hyper-CVD as salvage therapy for patients (pts) with R/R acute lymphoblastic leukemia (ALL). J Clin Oncol. 2017; 35(15 Suppl): 7025–7025.
  34. Kebriaei P, Cutler C, de Lima M, et al. Management of important adverse events associated with inotuzumab ozogamicin: expert panel review. Bone Marrow Transplant. 2018; 53(4): 449–456.
  35. Mohty M, Malard F, Abecassis M, et al. Sinusoidal obstruction syndrome/veno-occlusive disease: current situation and perspectives-a position statement from the European Society for Blood and Marrow Transplantation (EBMT). Bone Marrow Transplant. 2015; 50(6): 781–789.
  36. Dalle JH, Giralt SA. Hepatic veno-occlusive disease after hematopoietic stem cell transplantation: risk factors and stratification, prophylaxis, and treatment. Biol Blood Marrow Transplant. 2016; 22(3): 400–409.
  37. Rajvanshi P. Hepatic sinusoidal obstruction after gemtuzumab ozogamicin (Mylotarg) therapy. Blood. 2002; 99(7): 2310–2314.



Hematology in Clinical Practice