The Role of Immunotherapy in ALL and its Impact on Healthcare


Authors : Mahin Amir

Volume/Issue : Volume 9 - 2024, Issue 10 - October


Google Scholar : https://tinyurl.com/y9bndjrk

Scribd : https://tinyurl.com/52yr2apf

DOI : https://doi.org/10.38124/ijisrt/IJISRT24OCT1931

Note : A published paper may take 4-5 working days from the publication date to appear in PlumX Metrics, Semantic Scholar, and ResearchGate.


Abstract : Background ALL is a rare but aggressive malignant cancer caused by uncontrolled proliferation of lymphoblasts which disrupt normal organ function.  Review of Interventions In this article we will discuss how genomic medicine allows better risk stratification and early identification of certain genetic alterations. Different immunotherapies will be reviewed, their mechanism of action and novel upcoming therapies.  Assessment of Impact The addition of immunotherapy has improved clinical outcomes for patients, increasing overall survival and having a lower AE profile.  Conclusion Immunotherapy offers a more targeted approach in ALL management, despite high initial costs, it can prove to be cost-effective and inevitably reduce burden on a health system.

Keywords : Immunotherapy, Chemotherapy, Monoclonal Antibodies, Leukemia, Healthcare.

References :

  1. Key Statistics for Acute Lymphocytic Leukemia (ALL) [Internet]. www.cancer.org. 2023. Available from: https://www.cancer.org/cancer/types/acute-lymphocytic-leukemia/about/key-statistics.html
  2. Mavers M, Simonetta F, Hidekazu Nishikii, Ribado JV, Maas-Bauer K, Alvarez M, et al. Activation of the DR3-TL1A Axis in Donor Mice Leads to Regulatory T Cell Expansion and Activation With Reduction in Graft-Versus-Host Disease. Frontiers in Immunology. 2019 Jul 17;10.
  3. Bassan R, Bourquin JP, DeAngelo DJ, et al New approaches to the management of adult acute lymphoblastic leukemia. J Clin Oncol JCO2017773648, 2018.
  4. Eno J. Immunotherapy Through the Years. Journal of the Advanced Practitioner in Oncology [Internet]. 2017;8(7):747–53. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6188092/#:~:text=The%20first%20immunotherapy%20agent%2C%20an
  5. ‌Piccaluga PP, Arpinati M, Candoni A, et al. Surface antigens analysis reveals significant expression of candidate targets for immunotherapy in adult acute lymphoid leukemia. Leuk Lymphoma. 2011;52(2):325–327
  6. Maury S, Chevret S, Thomas X, Heim D, Leguay T, Huguet F, et al. Rituximab in B-Lineage Adult Acute Lymphoblastic Leukemia. New England Journal of Medicine. 2016 Sep 15;375(11):1044–53.
  7. Hoelzer D, Gökbuget N. Chemoimmunotherapy in acute lymphoblastic leukemia. Blood Rev. 2012;26(1):25–32
  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(24):3880–3889
  9. Thomas DA, 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. 
  10. Saleh MM, et al. (2020). The risk of hypogammaglobulinemia in patients receiving rituximab-based cancer treatments. PLoS ONE, 15(9), e0239351.
  11. Carson KR, et al. (2009). Progressive multifocal leukoencephalopathy after rituximab therapy in HIV-negative patients: A report of 57 cases from the Research on Adverse Drug Events and Reports project. Blood, 113(20), 4834-4840.
  12. Evens AM, et al. (2013). Neutropenia in CD20‐targeted therapy for non‐Hodgkin lymphomas: Risk factors and management. Leukemia & Lymphoma, 54(5), 971-974.
  13. Selby P, Kirsty Sharplin, Osborn M, Yeung DT. Management of Philadelphia Chromosome-positive Acute Lymphoblastic Leukaemia. 2023 Jan 1;289–310.
  14. Salles G, Barrett M, Foà R, Maurer J, O’Brien S, Valente N, et al. Rituximab in B-Cell Hematologic Malignancies: A Review of 20 Years of Clinical Experience. Advances in Therapy [Internet]. 2017;34(10):2232–73. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5656728/
  15. Martinelli G, Boissel N, Chevallier P, et al. Complete Hematologic and Molecular Response in Adult Patients With Relapsed/Refractory Philadelphia Chromosome-Positive B-Precursor Acute Lymphoblastic Leukemia Following Treatment With Blinatumomab: Results From a Phase II, Single-Arm, Multicenter Study. J Clin Oncol. 2017;35(16):1795-1802.
  16. Kantarjian H, Stein A, Gökbuget N, Fielding AK, Schuh AC, Ribera JM, et al. Blinatumomab versus Chemotherapy for Advanced Acute Lymphoblastic Leukemia. New England Journal of Medicine [Internet]. 2017 Mar 2;376(9):836–47. Available from: https://www.nejm.org/doi/full/10.1056/NEJMoa1609783
  17. Ahmadzadeh M, Johnson LA, Heemskerk B, Wunderlich JR, Dudley ME, White DE, et al. Tumor antigen–specific CD8 T cells infiltrating the tumor express high levels of PD-1 and are functionally impaired. Blood. 2009 Aug 20;114(8):1537–44.
  18. Salmaninejad A, Khoramshahi V, Azani A, Soltaninejad E, Aslani S, Zamani MR, et al. PD-1 and cancer: molecular mechanisms and polymorphisms. Immunogenetics. 2017 Jun 22;70(2):73–86.
  19. Price T, Chawla S, Falchook G, Prenen H, Lugowska I, Subbiah V, et al. 403 Early results from a phase 1 study to evaluate safety, pharmacokinetics, and efficacy of AMG 404, a programmed death-1 (PD-1) antibody, in patients with advanced solid tumors. Journal for ImmunoTherapy of Cancer [Internet]. 2020 Nov 1 [cited 2023 Nov 7];8(Suppl 3). Available from: https://jitc.bmj.com/content/8/Suppl_3/A245.1
  20. Maude SL, Frey N, Shaw PA, Aplenc R, Barrett DM, Bunin NJ, et al. Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med. 2014;371:1507–17.
  21. Turtle CJ, Hanafi L-A, Berger C, Gooley TA, Cherian S, Hudecek M, et al. CD19 CAR–T cells of defined CD4+: CD8+ composition in adult B cell ALL patients. J Clin Invest. 2016;126:2123–38.
  22. George S, Bell EJ, Zheng Y, Kim R, White J, Devgan G, et al. The Impact of Adverse Events on Health Care Resource Utilization, Costs, and Mortality Among Patients Treated with Immune Checkpoint Inhibitors. Oncologist [Internet]. 2021 Jul 1 [cited 2022 Mar 26];26(7):e1205–15. Available from: https://eds.p.ebscohost.com/eds/pdfviewer/pdfviewer?vid=7&sid=0a01afa3-4f63-4e21-a7ed-1e5d7579eee5%40redis
  23. Magee, et al. Adverse event profile for immunotherapy agents compared with chemotherapy in solid organ tumors: A systematic review and meta-analysis of randomized clinical trials [Internet]. Elsevier; 2020. Available from: https://www.sciencedirect.com/science/article/pii/S0923753419354638 
  24. CONFIDENTIAL UNTIL PUBLISHED Final appraisal determination -Pembrolizumab for untreated PD-L1-positive metastatic non-small-cell lung cancer Pembrolizumab for untreated PD-L1-positive metastatic non-small-cell lung cancer (CDF review of TA447) [Internet]. Available from: https://www.nice.org.uk/guidance/ta531/documents/final-appraisal-determination-document#:~:text=The%20average%20cost%20of%20a
  25. Zhang C, Zhang J, Tan J, Tian P, Li W. Cost-Effectiveness of Pembrolizumab for the treatment of Non–Small-Cell lung cancer: A systematic review. Frontiers in Oncology. 2022 Aug 26;12.
  26. Information Services Division A National Statistics publication for Scotland Cancer Mortality in Scotland [Internet]. 2019. Available from: https://www.isdscotland.org/Health-Topics/Cancer/Publications/2019-10-29/2019-10-29-Cancer-Mortality-Report.pdf
  27. Bhayat F, Das-Gupta E, Hubbard R. Bone marrow transplantation in AML, and socioeconomic class: a UK population-based cohort study. BMC Cancer. 2010 Sep 28;10(1).

Background ALL is a rare but aggressive malignant cancer caused by uncontrolled proliferation of lymphoblasts which disrupt normal organ function.  Review of Interventions In this article we will discuss how genomic medicine allows better risk stratification and early identification of certain genetic alterations. Different immunotherapies will be reviewed, their mechanism of action and novel upcoming therapies.  Assessment of Impact The addition of immunotherapy has improved clinical outcomes for patients, increasing overall survival and having a lower AE profile.  Conclusion Immunotherapy offers a more targeted approach in ALL management, despite high initial costs, it can prove to be cost-effective and inevitably reduce burden on a health system.

Keywords : Immunotherapy, Chemotherapy, Monoclonal Antibodies, Leukemia, Healthcare.

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