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Current Oncology Reports
Published in: Current Oncology Reports 5/2024

08-04-2024 | Checkpoint Inhibitors | REVIEW

Immune Checkpoint Inhibitors in Geriatric Oncology

Authors: Sarah L. Cook, Md Al Amin, Shahla Bari, Pradeep J. Poonnen, Mustafa Khasraw, Margaret O. Johnson

Published in: Current Oncology Reports | Issue 5/2024

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Abstract

Purpose of Review

This manuscript will update prior reviews of immune checkpoint inhibitors (ICIs) in light of basic science, translational, and clinical discoveries in the field of cancer immunology and aging.

Recent Findings

ICIs have led to significant advancements in the treatment of cancer. Landmark trials of ICIs have cited the efficacy and toxicity experienced by older patients, but most trials are not specifically designed to address outcomes in older patients. Underlying mechanisms of aging, like cellular senescence, affect the immune system and may ultimately alter the host’s response to ICIs. Validated tools are currently used to identify older adults who may be at greater risk of developing complications from their cancer treatment.

Summary

We review changes in the aging immune system that may alter responses to ICIs, report outcomes and toxicities in older adults from recent ICI clinical trials, and discuss clinical tools specific to older patients with cancer.
Literature
1.
Balducci L. Geriatric oncology, spirituality, and palliative care. J Pain Symptom Manage. 2019;57(1):171–5.PubMedCrossRef
2.
3.
Pilleron S, et al. International trends in cancer incidence in middle-aged and older adults in 44 countries. J Geriatr Oncol. 2022;13(3):346–55.PubMedCrossRef
4.
Lee L, Gupta M, Sahasranaman S. Immune checkpoint inhibitors: an introduction to the next-generation cancer immunotherapy. J Clin Pharmacol. 2016;56(2):157–69.PubMedCrossRef
5.
Yoo MJ, et al. Immune checkpoint inhibitors: An emergency medicine focused review. Am J Emerg Med. 2021;50:335–44.PubMedCrossRef
6.
7.
8.
9.
• Gorgoulis V, et al. Cellular senescence: defining a path forward. Cell. 2019;179(4):813–27. Describes the latest consensus from the International Cell Senescence Association on the key cellular and molecular features of senescence.PubMedCrossRef
10.
11.
12.
Ladomersky E, et al. Advanced age increases immunosuppression in the brain and decreases immunotherapeutic efficacy in subjects with glioblastoma. Clin Cancer Res. 2020;26(19):5232–45.PubMedPubMedCentralCrossRef
13.
Tsukamoto H, et al. Aging-associated and CD4 T-cell-dependent ectopic CXCL13 activation predisposes to anti-PD-1 therapy-induced adverse events. Proc Natl Acad Sci U S A. 2022;119(29):e2205378119.PubMedPubMedCentralCrossRef
14.
Sceneay J, et al. Interferon signaling is diminished with age and is associated with immune checkpoint blockade efficacy in triple-negative breast cancer. Cancer Discov. 2019;9(9):1208–27.PubMedCrossRef
15.
Nicoli F, et al. Primary immune responses are negatively impacted by persistent herpesvirus infections in older people: results from an observational study on healthy subjects and a vaccination trial on subjects aged more than 70 years old. EBioMedicine. 2022;76:103852.PubMedPubMedCentralCrossRef
16.
Fletcher JM, et al. Cytomegalovirus-specific CD4+ T cells in healthy carriers are continuously driven to replicative exhaustion. J Immunol. 2005;175(12):8218–25.PubMedCrossRef
17.
Tsukamoto H, et al. Age-associated increase in lifespan of naive CD4 T cells contributes to T-cell homeostasis but facilitates development of functional defects. Proc Natl Acad Sci U S A. 2009;106(43):18333–8.PubMedPubMedCentralCrossRef
18.
den Braber I, et al. Maintenance of peripheral naive T cells is sustained by thymus output in mice but not humans. Immunity. 2012;36(2):288–97.CrossRef
19.
Yang KY, et al. Single-cell transcriptomics of Treg reveals hallmarks and trajectories of immunological aging. J Leukoc Biol. 2023;115:19.CrossRef
20.
21.
Mahalingam SS, et al. Distinct SARS-CoV-2 specific NLRP3 and IL-1beta responses in T cells of aging patients during acute COVID-19 infection. Front Immunol. 2023;14:1231087.PubMedPubMedCentralCrossRef
22.
Osterholm MT, et al. Efficacy and effectiveness of influenza vaccines: a systematic review and meta-analysis. Lancet Infect Dis. 2012;12(1):36–44.PubMedCrossRef
23.
de Boer RJ, Tesselaar K, Borghans JAM. Better safe than sorry: naive T-cell dynamics in healthy ageing. Semin Immunol. 2023;70: 101839.PubMedCrossRef
24.
•• Soerens AG, et al. Functional T cells are capable of supernumerary cell division and longevity. Nature. 2023;614(7949):762–6. This article is able to show that T cells from a single mouse are able to to be expanded for over ten years, exceeding the mouse lifespan. These cells can remain competent to vaccination responses ater this time frame.PubMedCrossRef
25.
•• Zhang B, et al. Multi-omic rejuvenation and life span extension on exposure to youthful circulation. Nat Aging. 2023;3(8):948–64. This study shows that aged mice are able to have improved physiological outcomes when they share a circulatory system with a young mouse, with effects occuring on a physiological and molecular (including epigenetic) scale.PubMedCrossRef
26.
Wang TW, et al. Blocking PD-L1-PD-1 improves senescence surveillance and ageing phenotypes. Nature. 2022;611(7935):358–64.PubMedCrossRef
27.
28.
29.
•• Voruganti T, et al. Association between age and survival trends in advanced non-small cell lung cancer after adoption of immunotherapy. JAMA Oncol. 2023;9(3):334–41. This is a recent meta-analysis looking at outcomes in older patients with NSCLC receiving checkpoint inhibitors.PubMedPubMedCentralCrossRef
30.
Spigel DR, et al. Safety, efficacy, and patient-reported health-related quality of life and symptom burden with nivolumab in patients with advanced non-small cell lung cancer, including patients aged 70 years or older or with poor performance status (CheckMate 153). J Thorac Oncol. 2019;14(9):1628–39.PubMedCrossRef
31.
Felip E, et al. CheckMate 171: A phase 2 trial of nivolumab in patients with previously treated advanced squamous non-small cell lung cancer, including ECOG PS 2 and elderly populations. Eur J Cancer. 2020;127:160–72.PubMedCrossRef
32.
•• Blanco R, et al. Pembrolizumab as first-line treatment for advanced NSCLC in older adults: a phase II clinical trial evaluating geriatric and quality-of-life outcomes. Lung Cancer. 2023;183: 107318. This is a prospective ICI trial that also includes geriatric and quality -of-life outcomes.PubMedCrossRef
33.
Antonia SJ, et al. Durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer. N Engl J Med. 2017;377(20):1919–29.PubMedCrossRef
34.
Socinski MA, et al. Durvalumab after concurrent chemoradiotherapy in elderly patients with unresectable stage III non-small-cell lung cancer (PACIFIC). Clin Lung Cancer. 2021;22(6):549–61.PubMedCrossRef
35.
36.
37.
38.
39.
40.
Eggermont AMM, et al. Adjuvant pembrolizumab versus placebo in resected stage III melanoma. N Engl J Med. 2018;378(19):1789–801.PubMedCrossRef
41.
42.
Luke JJ, et al. Pembrolizumab versus placebo as adjuvant therapy in completely resected stage IIB or IIC melanoma (KEYNOTE-716): a randomised, double-blind, phase 3 trial. Lancet. 2022;399(10336):1718–29.PubMedCrossRef
43.
Weber J, et al. Adjuvant nivolumab versus ipilimumab in resected stage III or IV melanoma. N Engl J Med. 2017;377(19):1824–35.PubMedCrossRef
44.
Zimmer L, et al. Adjuvant nivolumab plus ipilimumab or nivolumab monotherapy versus placebo in patients with resected stage IV melanoma with no evidence of disease (IMMUNED): a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet. 2020;395(10236):1558–68.PubMedCrossRef
45.
Weber JS, et al. Adjuvant therapy of nivolumab combined with ipilimumab versus nivolumab alone in patients with resected stage IIIB-D or stage IV melanoma (CheckMate 915). J Clin Oncol. 2023;41(3):517–27.PubMedCrossRef
46.
47.
Robert C, et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med. 2015;372(4):320–30.PubMedCrossRef
48.
Robert C, et al. Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med. 2015;372(26):2521–32.PubMedCrossRef
49.
Bruijnen CP, et al. Frailty and checkpoint inhibitor toxicity in older patients with melanoma. Cancer. 2022;128(14):2746–52.PubMedCrossRef
50.
Tomita Y, et al. Efficacy and safety of avelumab plus axitinib in elderly patients with advanced renal cell carcinoma: extended follow-up results from JAVELIN Renal 101. ESMO Open. 2022;7(2): 100450.PubMedPubMedCentralCrossRef
51.
Pal SK, et al. Adjuvant atezolizumab versus placebo for patients with renal cell carcinoma at increased risk of recurrence following resection (IMmotion010): a multicentre, randomised, double-blind, phase 3 trial. Lancet. 2022;400(10358):1103–16.PubMedCrossRef
52.
Araujo DV, et al. Efficacy of immune-checkpoint inhibitors (ICI) in the treatment of older adults with metastatic renal cell carcinoma (mRCC) - an International mRCC Database Consortium (IMDC) analysis. J Geriatr Oncol. 2021;12(5):820–6.PubMedCrossRef
53.
Fujiwara Y, Miyashita H, Liaw BC. First-line therapy for elderly patients with advanced renal cell carcinoma in the immuno-oncology era: a network meta-analysis. Cancer Immunol Immunother. 2023;72(6):1355–64.PubMedCrossRef
54.
55.
Winer EP, et al. Pembrolizumab versus investigator-choice chemotherapy for metastatic triple-negative breast cancer (KEYNOTE-119): a randomised, open-label, phase 3 trial. Lancet Oncol. 2021;22(4):499–511.PubMedCrossRef
56.
Chen M, et al. Incidence and mortality trends in gastric cancer in the United States, 1992–2019. Int J Cancer. 2023;152(9):1827–36.PubMedCrossRef
57.
Kelly RJ, et al. Adjuvant nivolumab in resected esophageal or gastroesophageal junction cancer. N Engl J Med. 2021;384(13):1191–203.PubMedCrossRef
58.
Kang YK, et al. Nivolumab plus chemotherapy versus placebo plus chemotherapy in patients with HER2-negative, untreated, unresectable advanced or recurrent gastric or gastro-oesophageal junction cancer (ATTRACTION-4): a randomised, multicentre, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2022;23(2):234–47.PubMedCrossRef
59.
Janjigian YY, et al. First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial. Lancet. 2021;398(10294):27–40.PubMedPubMedCentralCrossRef
60.
Ebert MP, et al. Second-line therapy with nivolumab plus ipilimumab for older patients with oesophageal squamous cell cancer (RAMONA): a multicentre, open-label phase 2 trial. Lancet Healthy Longev. 2022;3(6):e417–27.PubMedCrossRef
61.
Tsakonas G, et al. Safety and efficacy of immune checkpoint blockade in patients with advanced nonsmall cell lung cancer and brain metastasis. Int J Cancer. 2023;153:1556.PubMedCrossRef
62.
Kreidieh FY, Tawbi HA. The introduction of LAG-3 checkpoint blockade in melanoma: immunotherapy landscape beyond PD-1 and CTLA-4 inhibition. Therapeutic Adv Med Oncol. 2023;15:17588359231186028.CrossRef
63.
Berghoff AS, et al. Immune checkpoint inhibitors in brain metastases: from biology to treatment. Am Soc Clin Oncol Educ Book. 2016;36:e116–22.CrossRef
64.
Lim M, et al. Phase III trial of chemoradiotherapy with temozolomide plus nivolumab or placebo for newly diagnosed glioblastoma with methylated MGMT promoter. Neuro Oncol. 2022;24(11):1935–49.PubMedPubMedCentralCrossRef
65.
Omuro A, et al. Radiotherapy combined with nivolumab or temozolomide for newly diagnosed glioblastoma with unmethylated MGMT promoter: an international randomized phase III trial. Neuro Oncol. 2023;25(1):123–34.PubMedCrossRef
66.
Bouffet E, et al. Immune checkpoint inhibition for hypermutant glioblastoma multiforme resulting from germline biallelic mismatch repair deficiency. J Clin Oncol. 2016;34(19):2206–11.PubMedCrossRef
67.
68.
69.
Luciani A, et al. Safety and effectiveness of immune checkpoint inhibitors in older patients with cancer: a systematic review of 48 real-world studies. Drugs Aging. 2021;38(12):1055–65.PubMedCrossRef
70.
Nebhan CA, et al. Clinical outcomes and toxic effects of single-agent immune checkpoint inhibitors among patients aged 80 years or older with cancer: a multicenter international cohort study. JAMA Oncol. 2021;7(12):1856–61.PubMedCrossRef
71.
Gomes F, et al. A prospective cohort study on the safety of checkpoint inhibitors in older cancer patients - the ELDERS study. ESMO Open. 2021;6(1): 100042.PubMedPubMedCentralCrossRef
72.
73.
Mohile SG, et al. Practical assessment and management of vulnerabilities in older patients receiving chemotherapy: ASCO guideline for geriatric oncology summary. J Oncol Pract. 2018;14(7):442–6.PubMedCrossRef
74.
Williams GR, et al. Practical assessment and management of vulnerabilities in older patients receiving systemic cancer therapy: ASCO guideline questions and answers. JCO Oncol Pract. 2023;19(9):718–23.PubMedCrossRef
75.
Gridelli C, et al. Immunotherapy in the first-line treatment of elderly patients with advanced non-small-cell lung cancer: results of an International Experts Panel Meeting by the Italian Association of Thoracic Oncology (AIOT). ESMO Open. 2023;8(2): 101192.PubMedPubMedCentralCrossRef
76.
Garcia MV, et al. Screening tools for identifying older adults with cancer who may benefit from a geriatric assessment: a systematic review. JAMA Oncol. 2021;7(4):616–27.PubMedCrossRef
77.
Chon J, et al. Validity of a self-administered G8 screening test for older patients with cancer. J Geriatr Oncol. 2023;14(7): 101553.PubMedCrossRef
Metadata
Title
Immune Checkpoint Inhibitors in Geriatric Oncology
Authors
Sarah L. Cook
Md Al Amin
Shahla Bari
Pradeep J. Poonnen
Mustafa Khasraw
Margaret O. Johnson
Publication date
08-04-2024
Publisher
Springer US
Published in
Current Oncology Reports / Issue 5/2024
Print ISSN: 1523-3790
Electronic ISSN: 1534-6269
DOI
https://doi.org/10.1007/s11912-024-01528-3

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