Blinatumomab, a Bispecific T-cell Engager (BiTE®) for CD-19 Targeted Cancer Immunotherapy: Clinical Pharmacology and Its Implications

Clinical Pharmacokinetics

Volumn 55, Issue 10, 2016, Pages 1271-1288

  Zhu, Min ^a   Wu, Benjamin ^a   Brandl, Christian ^b   Johnson, Jessica ^a   Wolf, Andreas ^b   Chow, Andrew ^a   Doshi, Sameer ^a  

^a AMGEN INC   (United States)

^b Amgen Research GmbH   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

BLINATUMOMAB; CREATININE; CYTOCHROME P450 1A2; CYTOCHROME P450 2C9; CYTOCHROME P450 3A4; GAMMA INTERFERON; INTERLEUKIN 10; INTERLEUKIN 2; INTERLEUKIN 4; INTERLEUKIN 6; TUMOR NECROSIS FACTOR; ANTINEOPLASTIC AGENT; BISPECIFIC ANTIBODY; CYTOKINE;

ACUTE LYMPHOBLASTIC LEUKEMIA; ADULT; AGE; AGED; ARTICLE; BODY WEIGHT; CANCER IMMUNOTHERAPY; CD3+ T LYMPHOCYTE; CLINICAL PHARMACOLOGY; CONTINUOUS INFUSION; CREATININE CLEARANCE; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG DISPOSITION; ELIMINATION HALF-LIFE; ENZYME ACTIVITY; FEMALE; HEPATIC CLEARANCE; HUMAN; HUMAN CELL; HUMORAL IMMUNE DEFICIENCY; IMMUNOGENICITY; KIDNEY FUNCTION; LIVER FUNCTION; LYMPHOCYTE COUNT; MAJOR CLINICAL STUDY; MALE; MILD RENAL IMPAIRMENT; MINIMAL RESIDUAL DISEASE; MODERATE RENAL IMPAIRMENT; NONHODGKIN LYMPHOMA; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; RENAL CLEARANCE; SEVERE RENAL IMPAIRMENT; SEX DIFFERENCE; STEADY STATE; TREATMENT DURATION; URINARY EXCRETION; URINE VOLUME; VOLUME OF DISTRIBUTION; B LYMPHOCYTE; CLINICAL TRIAL; DOSE RESPONSE; DRUG ADMINISTRATION; DRUG EFFECTS; HALF LIFE TIME; IMMUNOLOGY; KIDNEY FAILURE; LYMPHOMA, NON-HODGKIN; METABOLIC CLEARANCE RATE; METABOLISM; PHASE 1 CLINICAL TRIAL; PHASE 2 CLINICAL TRIAL; PRECURSOR B-CELL LYMPHOBLASTIC LEUKEMIA-LYMPHOMA; T LYMPHOCYTE;

AGE FACTORS; ANTIBODIES, BISPECIFIC; ANTINEOPLASTIC AGENTS; B-LYMPHOCYTES; BODY WEIGHT; CYTOKINES; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG ADMINISTRATION SCHEDULE; FEMALE; HALF-LIFE; HUMANS; LYMPHOMA, NON-HODGKIN; MALE; METABOLIC CLEARANCE RATE; PRECURSOR B-CELL LYMPHOBLASTIC LEUKEMIA-LYMPHOMA; RENAL INSUFFICIENCY; T-LYMPHOCYTES;

EID: 84969850918     PISSN: 03125963     EISSN: 11791926     Source Type: Journal    
DOI: 10.1007/s40262-016-0405-4     Document Type: Article

References (44)

1. Bargou R, Leo E, Zugmaier G, Klinger M, Goebeler M, Knop S, et al. Tumor regression in cancer patients by very low doses of a T cell-engaging antibody. Science. 2008;321:974–7.
2. Nagorsen D, Bargou R, Ruttinger D, Kufer P, Baeuerle PA, Zugmaier G. Immunotherapy of lymphoma and leukemia with T-cell engaging BiTE antibody blinatumomab. Leuk Lymphoma. 2009;50:886–91.
3. Blincyto™ (blinatumomab) prescribing information. Thousand Oaks, CA, USA: Amgen Inc.; 2014.
4. Przepiorka D, Ko C-W, Deisseroth A, Yancey CL, Candau-Chacon R, Chiu H-J, et al. FDA approval: blinatumomab. Clin Cancer Res. 2015;21:4035–9.
5. Klinger M, Brandl C, Zugmaier G, Hijazi Y, Bargou RC, Topp MS, et al. Immunopharmacologic response of patients with B-lineage acute lymphoblastic leukemia to continuous infusion of T cell-engaging CD19/CD3-bispecific BiTE antibody blinatumomab. Blood. 2012;119:6226–33.
6. Hijazi Y, Klinger M, Schub A, Wu B, Zhu M, Kufer P, et al. Blinatumomab exposure and pharmacodynamic response in patients with non-Hodgkin lymphoma (NHL). J Clin Oncol. 2013;31(15 suppl):Abstract 3051.
7. ®) antibody construct blinatumomab as a potential therapy. Int Immunol. 2015;27:31–7.
8. Topp MS, Gökbuget N, Stein AS, Zugmaier G, O’Brien S, Bargou RC, 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. Lancet Oncol. 2015;16:57–66.
9. Huehls AM, Coupet TA, Sentman CL. Bispecific T-cell engagers for cancer immunotherapy. Immunol Cell Biol. 2015;93:290–6.
10. Raponi S, De Propris MS, Intoppa S, Milani ML, Vitale A, Elia L, 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.
11. Nagorsen D, Baeuerle PA. Immunomodulatory therapy of cancer with T cell-engaging BiTE antibody blinatumomab. Exp Cell Res. 2011;317:1255–60.
12. Haas C, Krinner E, Brischwein K, Hoffmann P, Lutterbuse R, Schlereth B, et al. Mode of cytotoxic action of T cell-engaging BiTE antibody MT110. Immunobiology. 2009;214:441–53.
13. Anthony DA, Andrews DM, Watt SV, Trapani JA, Smyth MJ. Functional dissection of the granzyme family: cell death and inflammation. Immunol Rev. 2010;235:73–92.
14. Ewen CL, Kane KP, Bleackley RC. A quarter century of granzymes. Cell Death Differ. 2012;19:28–35.
15. Voskoboinik I, Dunstone MA, Baran K, Whisstock JC, Trapani JA. Perforin: structure, function, and role in human immunopathology. Immunol Rev. 2010;235:35–54.
16. Kontermann RE. Dual targeting strategies with bispecific antibodies. mAbs. 2012;4:182–197.
17. Rathi C, Meibohm B. Clinical pharmacology of bispecific antibody constructs. J Clin Pharmacol. 2015;55:S21–8.
18. Portell CA, Wenzell CM, Advani AS. Clinical and pharmacologic aspects of blinatumomab in the treatment of B-cell acute lymphoblastic leukemia. Clin Pharmacol. 2013;5:5–11.
19. Wu B, Sun YN. Pharmacokinetics of peptide-Fc fusion proteins. J Pharm Sci. 2014;103:53–64.
20. Fielding AK, Richards SM, Chopra R, Lazarus HM, Litzow MR, Buck G, et al. Outcome of 609 adults after relapse of acute lymphoblastic leukemia (ALL); an MRC UKALL12/ECOG 2993 study. Blood. 2007;109:944–50.
21. Oriol A, Vives S, Hernandez-Rivas JM, Tormo M, Heras I, Rivas C, et al. Outcome after relapse of acute lymphoblastic leukemia in adult patients included in four consecutive risk-adapted trials by the PETHEMA Study Group. Haematologica. 2010;95:589–96.
22. Nagorsen D. Blinatumomab (Blincyto™) indicated for the treatment of relapsed or refractory B-cell precursor acute lymphoblastic leukemia (Amgen, Inc.). In: Presented at: Accelerating anticancer agent development and validation workshop; May 6–8, 2015; Bethesda, MD, USA.
23. Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16:31–41.
24. Xu Y, Hijazi Y, Wolf A, Wu B, Sun YN, Zhu M. Physiologically based pharmacokinetic model to assess the influence of blinatumomab-mediated cytokine elevations on cytochrome P450 enzyme activity. CPT Pharmacomet Syst Pharmacol. 2015;4:507–15.
25. Schoen T, Blum J, Paccaud F, Burnier M, Bochud M, Conen D, et al. Factors associated with 24-hour urinary volume: the Swiss salt survey. BMC Nephrol. 2013;14:246.
26. Lobo ED, Hansen RJ, Balthasar JP. Antibody pharmacokinetics and pharmacodynamics. J Pharm Sci. 2004;93:2645–68.
27. Zhu M, Kratzer A, Johnson J, Holland C, Brandl C, Singh I, et al. Pharmacokinetics/pharmacodynamics (PKPD) of blinatumomab in patients with relapsed/refractory B-precursor acute lymphoblastic leukemia (r/r ALL). J Clin Oncol. 2015;33(15 Suppl):Abstract 2561.
28. Huang SM, Zhao H, Lee JI, Reynolds K, Zhang L, Temple R, et al. Therapeutic protein-drug interactions and implications for drug development. Clin Pharmacol Ther. 2010;87:497–503.
29. Sato AK, Viswanathan M, Kent RB, Wood CR. Therapeutic peptides: technological advances driving peptides into development. Curr Opin Biotechnol. 2006;17:638–42.
30. ® (Interferon alfa-2a) prescribing information. Basel, Switzerland: F. Hoffmann-La Roche Ltd.; 2001.
31. ® (filgrastim) prescribing information. Thousand Oaks, CA, USA: Amgen; 2015.
32. ® (imiglucerase for injection) prescribing information. Cambridge, MA, USA: Genzyme Corporation; 2011.
33. Wu B, Johnson J, Soto M, Ponce M, Calamba D, Sun YN. Investigation of the mechanism of clearance of AMG 386, a selective angiopoietin-1/2 neutralizing peptibody, in splenectomized, nephrectomized, and FcRn knockout rodent models. Pharm Res. 2012;29:1057–65.
34. Leader B, Baca QJ, Golan DE. Protein therapeutics: a summary and pharmacological classification. Nat Rev Drug Discov. 2008;7:21–39.
35. Zhao L, Ren TH, Wang DD. Clinical pharmacology considerations in biologics development. Acta Pharmacol Sin. 2012;33:1339–47.
36. Meibohm B, Zhou H. Characterizing the impact of renal impairment on the clinical pharmacology of biologics. J Clin Pharmacol. 2012;52:54S–62S.
37. US Food and Drug Administration. Guidance for industry: pharmacokinetics in patients with impaired renal function: study design, data analysis, and impact on dosing and labeling. Draft Guidance. 2010.
38. Meijer DKF, Ziegler K. Mechanisms for the hepatic clearance of oligopeptides and proteins: implications for rate of elimination, bioavailability, and cell-specific drug delivery to the liver. In: KL Audus TJRE, editor. Biological barriers to protein delivery. New York: Plenum Press; 1993. p. 339–407.
39. Hoffmann P, Hofmeister R, Brischwein K, Brandl C, Crommer S, Bargou R, et al. Serial killing of tumor cells by cytotoxic T cells redirected with a CD19-/CD3-bispecific single-chain antibody construct. Int J Cancer. 2005;115:98–104.
40. Lameris R, de Bruin RC, Schneiders FL, van Bergen en Henegouwen PM, Verheul HM, de Gruijl TD, et al. Bispecific antibody platforms for cancer immunotherapy. Crit Rev Oncol Hematol. 2014;92:153–65.
41. Klinger M, Kufer P, Kirchinger P, Lutterbuese P, Leo E, Reinhardt C, et al. T cell responses during long-term continuous infusion of MT103 (MEDI-538; anti-CD19 BiTE) in patients with relapsed B-NHL: data from dose-escalation study MT103-104. Blood (ASH Annual Meeting Abstracts). 2006;108:Abstract 2725.
42. ®) antibody construct, in patients with minimal residual disease B-precursor acute lymphoblastic leukemia (ALL). Blood (ASH Annual Meeting Abstracts). 2014;124:Abstract 379.
43. Schub A, Nagele V, Zugmaier G, Brandl C, Hijazi Y, Topp MS, et al. Immunopharmacodynamic response to blinatumomab in patients with relapsed/refractory B-precursor acute lymphoblastic leukemia (ALL). J Clin Oncol. 2013;31(15 suppl):Abstract 7020.
44. ®) antibody construct blinatumomab: primary analysis results from an open-label, phase 2 study. Blood (ASH Annual Meeting Abstracts). 2014;124:Abstract 4460.