Login Register Cart 0
Generic placeholder image

Current Cancer Therapy Reviews

Editor-in-Chief

ISSN (Print): 1573-3947
ISSN (Online): 1875-6301

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Occurrence and Severity of Adverse Reactions of Immune Checkpoint Inhibitors (PD-1 and PD L1) Based on Mordovian Dispensary Data Analysis

Author(s): Basheer Marzoog*

Volume 18, Issue 1, 2022

Published on: 05 August, 2021

Page: [51 - 56] Pages: 6

DOI: 10.2174/1573394717666210805120525

Price: $65

Abstract

Background: Recently, a novel therapeutic technique has been revealed to recruit PDL1 and PD1 inhibitors to promote and enhance the cytotoxic T cell activity in combating the tumor. But unfortunately, several followed patients who didn’t tolerate the drug appeared unfavorable autoimmune side effects, such as anemia, pneumonitis, hepatitis, colitis, in addition to fatigue/ asthenia, decreased appetite, nausea, cough, dyspnea, constipation.

Aim: To assess the severity of the adverse reactions of PD-1 and PD-L1 inhibitors in treating patients with positive PD-1 or PD-L1; non-small cell lung cancer patients (NSCLCs), small cell lung cancer (SCLC), nodular sclerosis Hodgkin lymphoma, classic Hodgkin's lymphoma, gastric cancer, renal cell carcinoma, caecal carcinoma, buccal mucosa carcinoma, nasopharyngeal carcinoma, laryngopharynx cancer, bladder cancer, cervical cancer, and melanoma.

Materials and Methods: The study data was collected and analyzed randomly from the period of January 2019 to November 2020 from the Mordovian oncological dispensary. The data are collected from the electronic archive of the hospital. Then, we followed up with the patients for the same period, and we recorded the presented adverse reactions. The patients received anti-tumor drug; PD-L1/PD-L inhibitors (Atezolizumab; 1200mg, Pembrolizumab; 200mg, and Nivolumab; 240mg or 3 mg/kg) every 21 or 14 days they got IV infusion of PD-1 and/or PD-L1 inhibitors. After the progression and metastasis of the tumor, the patients received a combination of chemotherapy prior to the immunotherapy.

Results: The analyzed data have shown 7.14% of the studied patients (n=28) have developed adverse reactions that ranged from mild to moderate severity (anemia and biochemical tests deviation).

Conclusion: These clinical findings supported the moderate risk of developing life-threatening adverse reactions after administration of immune checkpoint inhibitors (Nivolumab, Pembrolizumab, Atezolizumab) to patients with advanced-stage tumors. The patients who were treated with PD-1 inhibitors developed less severe adverse reactions than patients who were treated with PD-L1 inhibitors. The adverse reaction severity depends on the period of administration and the type of the treated tumor, which consequently determines the dose of immunotherapy. Also, the aggressiveness of the autoimmune reactions depends on the patient's immune state and its reactivity.

Keywords: Immunotherapy, checkpoint inhibitors, PD-L1 & PD-1, atezolizumab, pembrolizumab, nivolumab.

« Previous Next »
Graphical Abstract

[1]
Marchetti A, Di Lorito A, Buttitta F. Why anti-PD1/PDL1 therapy is so effective? Another piece in the puzzle. J Thorac Dis 2017; 9(12): 4863-6.
[http://dx.doi.org/10.21037/jtd.2017.11.105] [PMID: 29312678]
[2]
Guilleminault L, Carmier D, Heuzé-Vourc’h N, Diot P, Pichon E. Immunotherapy in non-small cell lung: inhibition of the PD1/PDL1 pathway.Revue de Pneumologie Clinique Elsevier Masson SAS. 2015; pp. 44-56.
[3]
Zuazo M, Gato-Cañas M, Llorente N, et al. Molecular mechanisms of programmed cell death-1 dependent T cell suppression: Relevance for immunotherapy. Ann Transl Med 2017; 5(19): 385-5.
[http://dx.doi.org/10.21037/atm.2017.06.11] [PMID: 29114543]
[4]
Shin DS, Zaretsky JM, Escuin-Ordinas H, et al. Primary resistance to pd-1 blockade mediated by jak1/2 mutations. Cancer Discov 2017; 7(2): 188-201.
[http://dx.doi.org/10.1158/2159-8290.CD-16-1223] [PMID: 27903500]
[5]
Curtsinger JM, Lins DC, Mescher MF. Signal 3 determines tolerance versus full activation of naive CD8 T cells: dissociating proliferation and development of effector function. J Exp Med 2003; 197(9): 1141-51.
[http://dx.doi.org/10.1084/jem.20021910] [PMID: 12732656]
[6]
Liechtenstein T, Perez-Janices N, Blanco-Luquin I, et al. Anti-melanoma vaccines engineered to simultaneously modulate cytokine priming and silence PD-L1 characterized using ex vivo myeloid-derived suppressor cells as a readout of therapeutic efficacy. OncoImmunology 2014; 3(7): e945378.
[http://dx.doi.org/10.4161/21624011.2014.945378] [PMID: 25954597]
[7]
Marchetti A, Barberis M, Franco R, et al. Multicenter comparison of 22c3 pharmdx (agilent) and sp263 (ventana) assays to test pd-l1 expression for nsclc patients to be treated with immune checkpoint inhibitors. J Thorac Oncol 2017; 12(11): 1654-63.
[http://dx.doi.org/10.1016/j.jtho.2017.07.031] [PMID: 28818609]
[8]
Topalian SL, Hodi FS, Brahmer JR, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med 2012; 366(26): 2443-54.
[http://dx.doi.org/10.1056/NEJMoa1200690] [PMID: 22658127]
[9]
Zhang L, Conejo-Garcia JR, Katsaros D, et al. Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. N Engl J Med 2003; 348(3): 203-13.
[http://dx.doi.org/10.1056/NEJMoa020177] [PMID: 12529460]
[10]
Ruggiero R, Fraenza F, Scavone C, et al. Immune checkpoint inhibitors and immune-related adverse drug reactions: Data from Italian pharmacovigilance database. Front Pharmacol 2020; 11: 830.
[http://dx.doi.org/10.3389/fphar.2020.00830] [PMID: 32581796]
[11]
Das S, Johnson DB. Immune-related adverse events and anti-tumor efficacy of immune checkpoint inhibitors. J Immunother Cancer 2019; 7(1): 306.
[http://dx.doi.org/10.1186/s40425-019-0805-8] [PMID: 31730012]
[12]
Fiala O, Sorejs O, Sustr J, Kucera R, Topolcan O, Finek J. Immune-related adverse effects and outcome of patients with cancer treated with immune checkpoint inhibitors. Anticancer Res 2020; 40(3): 1219-27.
[http://dx.doi.org/10.21873/anticanres.14063] [PMID: 32132018]
[13]
He C, Qu T. Immune checkpoint inhibitor-related cutaneous adverse events. Asia Pac J Clin Oncol 2020; 16(5): e149-53.
[http://dx.doi.org/10.1111/ajco.13364] [PMID: 32786166]
[14]
The American cancer society medical and editorial content. Immune checkpoint inhibitors and their side effects. Available from: https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/immunotherapy/immune-checkpoint-inhibitors.html
[15]
Grover S, Rahma O E, Hashemi N, Lim R M. Gastrointestinal and Hepatic Toxicities of checkpoint inhibitors: Algorithms for management. Am Soc Clin Oncol Educ B 2018; 38: 13-9.
[16]
LIBTAYO® (cemiplimab-rwlc): Official Healthcare Professional Website. Available from: https://www.libtayohcp.com/ [Accessed Dec 1, 2020]
[17]
DailyMed - TECENTRIQ- atezolizumab injection, solution. Available from: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6fa682c9-a312-4932-9831-f286908660ee [Accessed Nov 17, 2020]
[18]
Schmid P, Adams S, Rugo HS, et al. Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer. N Engl J Med 2018; 379(22): 2108-21.
[19]
Facchinetti F, Bordi P, Leonetti A, Buti S, Tiseo M. Profile of atezolizumab in the treatment of metastatic non-small-cell lung cancer: Patient selection and perspectives. Drug Des Devel Ther 2018; 12: 2857-73.
[http://dx.doi.org/10.2147/DDDT.S124380] [PMID: 30237696]
[20]
Highlights of prescribing information. Available from: www.fda.gov/medwatch [Accessed Dec 1, 2020]
[21]
Immune-Mediated Adverse Reactions Management Guide. Available from: https://www.opdivohcp.com/assets/commercial/us/opdivo-hcp-pan-tumor/en/pdf/Immune_Mediated_Adverse_Management_Guide.pdf [Accessed Dec 2, 2020]
[22]
Morgado M, Plácido A, Morgado S, Roque F. Management of the adverse effects of immune checkpoint inhibitors. Vaccines (Basel) 2020; 8(4): 575.
[http://dx.doi.org/10.3390/vaccines8040575] [PMID: 33019641]
[23]
Zhou X, Yao Z, Yang H, Liang N, Zhang X, Zhang F. Are immune-related adverse events associated with the efficacy of immune checkpoint inhibitors in patients with cancer? A systematic review and meta-analysis. BMC Med 2020; 18(1): 87.
[http://dx.doi.org/10.1186/s12916-020-01549-2] [PMID: 32306958]
[24]
Martins F, Sofiya L, Sykiotis GP, et al. Adverse effects of immune-checkpoint inhibitors: epidemiology, management and surveillance. Nat Rev Clin Oncol 2019; 16(9): 563-80.
[http://dx.doi.org/10.1038/s41571-019-0218-0] [PMID: 31092901]

Rights & Permissions Print Cite
Article Metrics
38
1
© 2024 Bentham Science Publishers | Privacy Policy