Review Article | | Peer-Reviewed

Antibody-Drug Conjugate in the Treatment of Pediatric AML and ALL: A Review

Received: 11 December 2023    Accepted: 2 January 2024    Published: 11 January 2024
Views:       Downloads:
Abstract

Purpose: Antibody-drug conjugate has certain advantages in the treatment of childhood leukemia, which can improve the therapeutic effect and reduce toxic side effects. In this review, we try to collect all available human and pre-clinical data from 2021 to 2023 in this field. Methods: The search was done in PubMed database, using the following keywords: "Leukemia," "Inotuzumab ozogamicin," "Gemtuzumab ozogamicin," "Antibody drug conjugate," "Pediatric," "Children," "Childhood," In vitro studies, animal studies or clinical studies focusing solely on pharmacokinetics, pharmacoeconomics or safety were discarded. This review focuses on clinical outcomes including the assessment of complete response rate, adverse drug reactions and event free survival. Other clinical outcomes taken into account were adjunctive medications, relapse or motality. Results: Based on 16 included studies in this review, the vast majority of patients achieved hematologic remission with ADC therapy. The adverse reactions caused by ADC recorded in all studies include: neutropenia with fever, gastrointestinal symptoms, VOD, cytokine syndrome, infection, sepsis, gastrointestinal symptoms, hyperglycemia, hyperphosphatemia, anemia, thrombocytopenia, tumor lysis syndrome, liver function damage, altered mental state and abdominal swelling. Conclusion: Further studies are required to determine the optimal dose, duration, and the best formulation of ADC to prevent and/or manage chemotherapy-induced complications.

Published in International Journal of Clinical and Experimental Medical Sciences (Volume 10, Issue 1)
DOI 10.11648/j.ijcems.20241001.11
Page(s) 1-10
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2024. Published by Science Publishing Group

Keywords

Antibody-Drug Conjugate, Leukemia, Gemtuzumab Ozogamicin, Inotuzumab Ozogamicin, Adverse Reactions

References
[1] Pui, C. H., et al., Childhood Acute Lymphoblastic Leukemia: Progress Through Collaboration. J Clin Oncol, 2015. 33(27): p. 2938-48.
[2] Creutzig, U., et al., Diagnosis and management of acute myeloid leukemia in children and adolescents: recommendations from an international expert panel. Blood, 2012. 120(16): p. 3187-205.
[3] Inaba, H., M. Greaves, and C. G. Mullighan, Acute lymphoblastic leukaemia. Lancet, 2013. 381(9881): p. 1943-55.
[4] Dohner, H., et al., Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood, 2017. 129(4): p. 424-447.
[5] Pui, C. H. and W. E. Evans, Treatment of acute lymphoblastic leukemia. N Engl J Med, 2006. 354(2): p. 166-78.
[6] Inaba, H. and C. G. Mullighan, Pediatric acute lymphoblastic leukemia. Haematologica, 2020. 105(11): p. 2524-2539.
[7] Jabbour, E., et al., New insights into the pathophysiology and therapy of adult acute lymphoblastic leukemia. Cancer, 2015. 121(15): p. 2517-28.
[8] Lejman, M., et al., Targeted Therapy in the Treatment of Pediatric Acute Lymphoblastic Leukemia-Therapy and Toxicity Mechanisms. Int J Mol Sci, 2021. 22(18).
[9] Leung, D., et al., Antibody Conjugates-Recent Advances and Future Innovations. Antibodies (Basel), 2020. 9(1).
[10] Khongorzul, P., et al., Antibody-Drug Conjugates: A Comprehensive Review. Mol Cancer Res, 2020. 18(1): p. 3-19.
[11] Beck, A., et al., Strategies and challenges for the next generation of antibody-drug conjugates. Nat Rev Drug Discov, 2017. 16(5): p. 315-337.
[12] Carter, P. J. and P. D. Senter, Antibody-drug conjugates for cancer therapy. Cancer J, 2008. 14(3): p. 154-69.
[13] Lambert, J. M. and A. Berkenblit, Antibody-Drug Conjugates for Cancer Treatment. Annu Rev Med, 2018. 69: p. 191-207.
[14] Mullard, A., Maturing antibody-drug conjugate pipeline hits 30. Nat Rev Drug Discov, 2013. 12(5): p. 329-32.
[15] Ducry, L. and B. Stump, Antibody-drug conjugates: linking cytotoxic payloads to monoclonal antibodies. Bioconjug Chem, 2010. 21(1): p. 5-13.
[16] Kulkarni, A. A. and H. J. Gukasyan, Antibody-Drug Conjugates. Pharm Res, 2015. 32(11): p. 3451-2.
[17] Thomas, A., B. A. Teicher, and R. Hassan, Antibody-drug conjugates for cancer therapy. Lancet Oncol, 2016. 17(6): p. e254-e262.
[18] Gauzy-Lazo, L., I. Sassoon, and M. P. Brun, Advances in Antibody-Drug Conjugate Design: Current Clinical Landscape and Future Innovations. SLAS Discov, 2020. 25(8): p. 843-868.
[19] McCombs, J. R. and S. C. Owen, Antibody drug conjugates: design and selection of linker, payload and conjugation chemistry. AAPS J, 2015. 17(2): p. 339-51.
[20] Chudasama, V., A. Maruani, and S. Caddick, Recent advances in the construction of antibody-drug conjugates. Nat Chem, 2016. 8(2): p. 114-9.
[21] Fatima, S. W. and S. K. Khare, Benefits and challenges of antibody drug conjugates as novel form of chemotherapy. J Control Release, 2022. 341: p. 555-565.
[22] Desai, A., et al., Antibody-drug conjugates: A promising novel therapeutic approach in lung cancer. Lung Cancer, 2022. 163: p. 96-106.
[23] Drago, J. Z., S. Modi, and S. Chandarlapaty, Unlocking the potential of antibody-drug conjugates for cancer therapy. Nat Rev Clin Oncol, 2021. 18(6): p. 327-344.
[24] Tarantino, P., et al., Antibody-drug conjugates: Smart chemotherapy delivery across tumor histologies. CA Cancer J Clin, 2022. 72(2): p. 165-182.
[25] Chia, C. S. B., A Patent Review on FDA-Approved Antibody-Drug Conjugates, Their Linkers and Drug Payloads. ChemMedChem, 2022. 17(11): p. e202200032.
[26] Merli, M., et al., New uses for brentuximab vedotin and novel antibody drug conjugates in lymphoma. Expert Rev Hematol, 2016. 9(8): p. 767-80.
[27] Kovtun, Y., et al., IMGN779, a Novel CD33-Targeting Antibody-Drug Conjugate with DNA-Alkylating Activity, Exhibits Potent Antitumor Activity in Models of AML. Mol Cancer Ther, 2018. 17(6): p. 1271-1279.
[28] Lanza, F., et al., CD22 Expression in B-Cell Acute Lymphoblastic Leukemia: Biological Significance and Implications for Inotuzumab Therapy in Adults. Cancers (Basel), 2020. 12(2).
[29] Thota, S. and A. Advani, Inotuzumab ozogamicin in relapsed B-cell acute lymphoblastic leukemia. Eur J Haematol, 2017. 98(5): p. 425-434.
[30] Vollmar, B. S., et al., Calicheamicin Antibody-Drug Conjugates with Improved Properties. Mol Cancer Ther, 2021. 20(6): p. 1112-1120.
[31] Agrawal, V., et al., Post-Transplantation Sinusoidal Obstruction Syndrome in Adult Patients with B Cell Acute Lymphoblastic Leukemia Treated with Pretransplantation Inotuzumab. Transplant Cell Ther, 2023. 29(5): p. 314-320.
[32] Brivio, E., et al., A phase 1 study of inotuzumab ozogamicin in pediatric relapsed/refractory acute lymphoblastic leukemia (ITCC-059 study). Blood, 2021. 137(12): p. 1582-1590.
[33] McCall, D., et al., Mini-hyper CVD + CRIB (condensed rituximab, inotuzumab ozogamicin, and blinatumomab) for refractory pediatric B-acute lymphoblastic leukemia. Pediatr Blood Cancer, 2023. 70(1): p. e29939.
[34] Uchida, E., et al., Sequential Therapy of Inotuzumab Ozogamicin and Blinatumomab as a Bridge-to Hematopoietic Stem Cell Transplantation in a Pediatric Patient With Primary Refractory Acute Lymphoblastic Leukemia: A Case Report. J Pediatr Hematol Oncol, 2021. 43(8): p. e1228-e1230.
[35] Murillo, L., et al., Use of inotuzumab-ozogamicin in a child with Down syndrome and refractory B-cell precursor acute lymphoblastic leukemia. Pediatr Blood Cancer, 2019. 66(4): p. e27562.
[36] Goebeler, M. E. and R. Bargou, Blinatumomab: a CD19/CD3 bispecific T cell engager (BiTE) with unique anti-tumor efficacy. Leuk Lymphoma, 2016. 57(5): p. 1021-32.
[37] Kantarjian, H., et al., Blinatumomab versus Chemotherapy for Advanced Acute Lymphoblastic Leukemia. N Engl J Med, 2017. 376(9): p. 836-847.
[38] Locatelli, F., et al., Effect of Blinatumomab vs Chemotherapy on Event-Free Survival Among Children With High-risk First-Relapse B-Cell Acute Lymphoblastic Leukemia: A Randomized Clinical Trial. JAMA, 2021. 325(9): p. 843-854.
[39] Kovtun, Y., et al., A CD123-targeting antibody-drug conjugate, IMGN632, designed to eradicate AML while sparing normal bone marrow cells. Blood Adv, 2018. 2(8): p. 848-858.
[40] Flynn, M. J., et al., ADCT-301, a Pyrrolobenzodiazepine (PBD) Dimer-Containing Antibody-Drug Conjugate (ADC) Targeting CD25-Expressing Hematological Malignancies. Mol Cancer Ther, 2016. 15(11): p. 2709-2721.
[41] Wu, J., et al., AFM13: a first-in-class tetravalent bispecific anti-CD30/CD16A antibody for NK cell-mediated immunotherapy. J Hematol Oncol, 2015. 8: p. 96.
[42] Caimi, P. F., et al., Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma (LOTIS-2): a multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol, 2021. 22(6): p. 790-800.
[43] Tilly, H., et al., Polatuzumab Vedotin in Previously Untreated Diffuse Large B-Cell Lymphoma. N Engl J Med, 2022. 386(4): p. 351-363.
[44] Budde, L. E., et al., Safety and efficacy of mosunetuzumab, a bispecific antibody, in patients with relapsed or refractory follicular lymphoma: a single-arm, multicentre, phase 2 study. Lancet Oncol, 2022. 23(8): p. 1055-1065.
[45] Godwin, C. D., R. P. Gale, and R. B. Walter, Gemtuzumab ozogamicin in acute myeloid leukemia. Leukemia, 2017. 31(9): p. 1855-1868.
[46] Pollard, J. A., et al., Gemtuzumab Ozogamicin Improves Event-Free Survival and Reduces Relapse in Pediatric KMT2A-Rearranged AML: Results From the Phase III Children's Oncology Group Trial AAML0531. J Clin Oncol, 2021. 39(28): p. 3149-3160.
[47] Gamis, A. S., et al., Gemtuzumab ozogamicin in children and adolescents with de novo acute myeloid leukemia improves event-free survival by reducing relapse risk: results from the randomized phase III Children's Oncology Group trial AAML0531. J Clin Oncol, 2014. 32(27): p. 3021-32.
[48] Wolska-Washer, A. and T. Robak, Safety and Tolerability of Antibody-Drug Conjugates in Cancer. Drug Saf, 2019. 42(2): p. 295-314.
[49] Masters, J. C., et al., Clinical toxicity of antibody drug conjugates: a meta-analysis of payloads. Invest New Drugs, 2018. 36(1): p. 121-135.
[50] Connors, J. M., et al., Brentuximab Vedotin with Chemotherapy for Stage III or IV Hodgkin's Lymphoma. N Engl J Med, 2018. 378(4): p. 331-344.
[51] Lambert, J., et al., Gemtuzumab ozogamicin for de novo acute myeloid leukemia: final efficacy and safety updates from the open-label, phase III ALFA-0701 trial. Haematologica, 2019. 104(1): p. 113-119.
[52] Pena Domingo, M., et al., Low doses of gemtuzumab ozogamicin in adults diagnosed with acute myeloid leukaemia. Med Clin (Barc), 2021. 157(7): p. 325-328.
[53] Li, T., et al., Chemotherapy and peripheral neuropathy. Neurol Sci, 2021. 42(10): p. 4109-4121.
[54] Richardson, D. L., Ocular toxicity and mitigation strategies for antibody drug conjugates in gynecologic oncology. Gynecol Oncol Rep, 2023. 46: p. 101148.
[55] Mahalingaiah, P. K., et al., Potential mechanisms of target-independent uptake and toxicity of antibody-drug conjugates. Pharmacol Ther, 2019. 200: p. 110-125.
[56] Paul, M. R., et al., Treatment of Recurrent Refractory Pediatric Pre-B Acute Lymphoblastic Leukemia Using Inotuzumab Ozogamicin Monotherapy Resulting in CD22 Antigen Expression Loss as a Mechanism of Therapy Resistance. J Pediatr Hematol Oncol, 2019. 41(8): p. e546-e549.
[57] Zwaan, C. M., et al., Gemtuzumab ozogamicin in pediatric CD33-positive acute lymphoblastic leukemia: first clinical experiences and relation with cellular sensitivity to single agent calicheamicin. Leukemia, 2003. 17(2): p. 468-70.
[58] Akazawa, R., et al., Inotuzumabozogamicin is an effective treatment for CD22-positive acute undifferentiated leukemia: A case report. Pediatr Blood Cancer, 2021. 68(5): p. e28976.
[59] Giugliano, F., et al., Bystander effect of antibody-drug conjugates: fact or fiction? Curr Oncol Rep, 2022. 24(7): p. 809-817.
[60] Wang, W. and C. J. Roberts, Protein aggregation - Mechanisms, detection, and control. Int J Pharm, 2018. 550(1-2): p. 251-268.
[61] Liang, K., et al., Dynamics of Endocytosis and Degradation of Antibody-Drug Conjugate T-DM1 in HER2 Positive Cancer Cells. Drug Des Devel Ther, 2021. 15: p. 5135-5150.
[62] Mahmood, I., Clinical Pharmacology of Antibody-Drug Conjugates. Antibodies (Basel), 2021. 10(2).
[63] Cabaud, O., et al., Overcoming Resistance to Anti-Nectin-4 Antibody-Drug Conjugate. Mol Cancer Ther, 2022. 21(7): p. 1227-1235.
[64] Martin, C., et al., Antibody-drug conjugates: Design and development for therapy and imaging in and beyond cancer, LabEx MAbImprove industrial workshop, July 27-28, 2017, Tours, France. MAbs, 2018. 10(2): p. 210-221.
[65] Tsuchikama, K. and Z. An, Antibody-drug conjugates: recent advances in conjugation and linker chemistries. Protein Cell, 2018. 9(1): p. 33-46.
Cite This Article
  • APA Style

    Liu, Z., Fan, L., Fan, X., Hu, S., Zhou, M. (2024). Antibody-Drug Conjugate in the Treatment of Pediatric AML and ALL: A Review. International Journal of Clinical and Experimental Medical Sciences, 10(1), 1-10. https://doi.org/10.11648/j.ijcems.20241001.11

    Copy | Download

    ACS Style

    Liu, Z.; Fan, L.; Fan, X.; Hu, S.; Zhou, M. Antibody-Drug Conjugate in the Treatment of Pediatric AML and ALL: A Review. Int. J. Clin. Exp. Med. Sci. 2024, 10(1), 1-10. doi: 10.11648/j.ijcems.20241001.11

    Copy | Download

    AMA Style

    Liu Z, Fan L, Fan X, Hu S, Zhou M. Antibody-Drug Conjugate in the Treatment of Pediatric AML and ALL: A Review. Int J Clin Exp Med Sci. 2024;10(1):1-10. doi: 10.11648/j.ijcems.20241001.11

    Copy | Download

  • @article{10.11648/j.ijcems.20241001.11,
      author = {Zhe Liu and Liyan Fan and Xuchen Fan and Shaoyan Hu and Mi Zhou},
      title = {Antibody-Drug Conjugate in the Treatment of Pediatric AML and ALL: A Review},
      journal = {International Journal of Clinical and Experimental Medical Sciences},
      volume = {10},
      number = {1},
      pages = {1-10},
      doi = {10.11648/j.ijcems.20241001.11},
      url = {https://doi.org/10.11648/j.ijcems.20241001.11},
      eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ijcems.20241001.11},
      abstract = {Purpose: Antibody-drug conjugate has certain advantages in the treatment of childhood leukemia, which can improve the therapeutic effect and reduce toxic side effects. In this review, we try to collect all available human and pre-clinical data from 2021 to 2023 in this field. Methods: The search was done in PubMed database, using the following keywords: "Leukemia," "Inotuzumab ozogamicin," "Gemtuzumab ozogamicin," "Antibody drug conjugate," "Pediatric," "Children," "Childhood," In vitro studies, animal studies or clinical studies focusing solely on pharmacokinetics, pharmacoeconomics or safety were discarded. This review focuses on clinical outcomes including the assessment of complete response rate, adverse drug reactions and event free survival. Other clinical outcomes taken into account were adjunctive medications, relapse or motality. Results: Based on 16 included studies in this review, the vast majority of patients achieved hematologic remission with ADC therapy. The adverse reactions caused by ADC recorded in all studies include: neutropenia with fever, gastrointestinal symptoms, VOD, cytokine syndrome, infection, sepsis, gastrointestinal symptoms, hyperglycemia, hyperphosphatemia, anemia, thrombocytopenia, tumor lysis syndrome, liver function damage, altered mental state and abdominal swelling. Conclusion: Further studies are required to determine the optimal dose, duration, and the best formulation of ADC to prevent and/or manage chemotherapy-induced complications.
    },
     year = {2024}
    }
    

    Copy | Download

  • TY  - JOUR
    T1  - Antibody-Drug Conjugate in the Treatment of Pediatric AML and ALL: A Review
    AU  - Zhe Liu
    AU  - Liyan Fan
    AU  - Xuchen Fan
    AU  - Shaoyan Hu
    AU  - Mi Zhou
    Y1  - 2024/01/11
    PY  - 2024
    N1  - https://doi.org/10.11648/j.ijcems.20241001.11
    DO  - 10.11648/j.ijcems.20241001.11
    T2  - International Journal of Clinical and Experimental Medical Sciences
    JF  - International Journal of Clinical and Experimental Medical Sciences
    JO  - International Journal of Clinical and Experimental Medical Sciences
    SP  - 1
    EP  - 10
    PB  - Science Publishing Group
    SN  - 2469-8032
    UR  - https://doi.org/10.11648/j.ijcems.20241001.11
    AB  - Purpose: Antibody-drug conjugate has certain advantages in the treatment of childhood leukemia, which can improve the therapeutic effect and reduce toxic side effects. In this review, we try to collect all available human and pre-clinical data from 2021 to 2023 in this field. Methods: The search was done in PubMed database, using the following keywords: "Leukemia," "Inotuzumab ozogamicin," "Gemtuzumab ozogamicin," "Antibody drug conjugate," "Pediatric," "Children," "Childhood," In vitro studies, animal studies or clinical studies focusing solely on pharmacokinetics, pharmacoeconomics or safety were discarded. This review focuses on clinical outcomes including the assessment of complete response rate, adverse drug reactions and event free survival. Other clinical outcomes taken into account were adjunctive medications, relapse or motality. Results: Based on 16 included studies in this review, the vast majority of patients achieved hematologic remission with ADC therapy. The adverse reactions caused by ADC recorded in all studies include: neutropenia with fever, gastrointestinal symptoms, VOD, cytokine syndrome, infection, sepsis, gastrointestinal symptoms, hyperglycemia, hyperphosphatemia, anemia, thrombocytopenia, tumor lysis syndrome, liver function damage, altered mental state and abdominal swelling. Conclusion: Further studies are required to determine the optimal dose, duration, and the best formulation of ADC to prevent and/or manage chemotherapy-induced complications.
    
    VL  - 10
    IS  - 1
    ER  - 

    Copy | Download

Author Information
  • Department of Pharmacy, The First Affiliated Hospital of Bengbu Medical University, Bengbu, China

  • Department of Hematology, Children's Hospital of Soochow University, Suzhou, China

  • Department of Pharmacy, The First Affiliated Hospital of Bengbu Medical University, Bengbu, China

  • Department of Hematology, Children's Hospital of Soochow University, Suzhou, China

  • Department of Pharmacy, Children's Hospital of Soochow University, Suzhou, China

  • Sections