ABSTRACT
Background
Cancer patients with pre-existing autoimmune diseases (AID) have been traditionally
excluded from clinical trials of immune checkpoint inhibitors (ICI) due to concerns
for toxicity. As indications for ICI expand, more data are needed on the safety and
efficacy of ICI treatment in cancer patients with AID.
Methods
We systematically searched for studies consisting of NSCLC, AID, ICI, treatment response,
and adverse events. Outcomes of interest include incidence of autoimmune flare, irAE,
response rate, and ICI discontinuation. Study data were pooled using random-effects
meta-analysis.
Results
Data were extracted from 24 cohort studies, consisting of 11,567 cancer patients (3774
NSCLC patients and 1157 with AID). Pooled analysis revealed an AID flare incidence
of 36% (95%CI 27%-46%) in all cancers and 23% (95%CI 9%-40%) in NSCLC. Pre-existing
AID was associated with an increased risk of de novo irAE in all cancer patients (RR
1.38, 95%CI 1.16-1.65) and NSCLC patients (RR 1.51, 95%CI 1.12-2.03). There was no
difference in de novo grade 3-4 irAE and tumor response between cancer patients with
and without AID. However, in NSCLC patients, pre-existing AID was associated with
a 2-fold increased risk of de novo grade 3-4 irAE (RR 1.95, 95%CI 1.01-3.75) but also
better tumor response in achieving a complete or partial response (RR 1.56, 95%CI
1.19-2.04).
Conclusions
NSCLC patients with AID are at a higher risk of grade 3-4 irAE but are more likely
to achieve treatment response. Prospective studies focused on optimizing immunotherapeutic
strategies are needed to improve outcomes for NSCLC patients with AID.
MINI-ABSTRACT
We evaluated the safety and efficacy of immune checkpoint inhibitors (ICI) in cancer
patients with pre-existing autoimmune diseases (AID). A meta-analysis of 24 cohort
studies showed that NSCLC patients with AID had an increased risk of de novo grade
3-4 irAE but were more likely to achieve treatment response. The study underscores
the need for prospective studies to optimize immunotherapeutic strategies for NSCLC
patients with AID.
Keywords
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Reference
- Immune-checkpoint inhibitors: Long-term implications of toxicity.Nature Reviews Clinical Oncology. 2022; 19: 254-267
- Immune-related adverse events with immune checkpoint blockade: a comprehensive review.European journal of cancer. 2016; 54: 139-148
- Prevalence of autoimmune disease among patients with lung cancer: implications for immunotherapy treatment options.JAMA oncology. 2016; 2: 1507-1508
- Use of immune checkpoint inhibitors in the treatment of patients with cancer and preexisting autoimmune disease: a systematic review.Annals of internal medicine. 2018; 168: 121-130
- Immune checkpoint inhibitors therapies in patients with cancer and preexisting autoimmune diseases: A meta-analysis of observational studies.Autoimmunity Reviews. 2020; 19102687
- The PRISMA 2020 statement: an updated guideline for reporting systematic reviews.International journal of surgery. 2021; 88105906
Aung WY, Seetharamu N, Lee C-S, Wang K. Immunotherapy in advanced stage NSCLC patients with pre-existing autoimmune disease: Systematic review and meta-analysis. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD4202231108. Accessed.
Wells GA, Shea B, O'Connell D, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. In: Oxford; 2000.
- The Cochrane Collaboration's tool for assessing risk of bias in randomised trials.Bmj. 2011; : 343
- Research electronic data capture (REDCap)—a metadata-driven methodology and workflow process for providing translational research informatics support.Journal of biomedical informatics. 2009; 42: 377-381
- Pembrolizumab for advanced non-small cell lung cancer (NSCLC): Impact of autoimmune comorbidity and outcomes following treatment completion.Journal of Oncology Pharmacy Practice. 2022; 10781552221079356
- Primary results from TAIL: a global single-arm safety study of atezolizumab monotherapy in a diverse population of patients with previously treated advanced non-small cell lung cancer.Journal for immunotherapy of cancer. 2021; 9
- Two-year survival with nivolumab in previously treated advanced non–small-cell lung cancer: A real-world pooled analysis of patients from France, Germany, and Canada.Lung Cancer. 2021; 157: 40-47
- Efficacy and safety of nivolumab in non-small cell lung cancer with preexisting interstitial lung disease.Thoracic cancer. 2018; 9: 847-855
- Safety of programmed Death–1 pathway inhibitors among patients with Non–Small-Cell lung cancer and preexisting autoimmune disorders.Journal of Clinical Oncology. 2018; 36: 1905
- Immune checkpoint inhibitor related myasthenia gravis: single center experience and systematic review of the literature.Journal for immunotherapy of cancer. 2019; 7: 1-11
- Tumor expression and usefulness as a biomarker of programmed death ligand 1 in advanced non-small cell lung cancer patients with preexisting interstitial lung disease.Medical Oncology. 2019; 36: 1-8
- Non-inferior clinical outcomes of immune checkpoint inhibitors in non-small cell lung cancer patients with interstitial lung disease.Lung Cancer. 2021; 155: 120-126
- Safety and efficacy of PD-1/PD-L1 blockade in patients with preexisting antinuclear antibodies.Clinical and Translational Oncology. 2020; 22: 919-927
- Immune checkpoint inhibitor therapy in patients with preexisting inflammatory bowel disease.Journal of Clinical Oncology. 2020; 38: 576
- Clinical outcomes of patients with advanced cancer and pre-existing autoimmune diseases treated with anti-programmed death-1 immunotherapy: A real-world transverse study.The oncologist. 2019; 24: e327
- Safety and efficacy of anti-programmed death 1 antibodies in patients with cancer and pre-existing autoimmune or inflammatory disease.European Journal of Cancer. 2018; 91: 21-29
- Risk of toxicity after initiating immune checkpoint inhibitor treatment in patients with rheumatoid arthritis.JCR: Journal of Clinical Rheumatology. 2021; 27: 267-271
- Real-world safety and efficacy data of immunotherapy in patients with cancer and autoimmune disease: the experience of the Hellenic Cooperative Oncology Group.Cancer Immunology, Immunotherapy. 2022; 71: 327-337
- Preexisting autoimmune disease and immune-related adverse events associated with anti-PD-1 cancer immunotherapy: a national case series from the Canadian Research Group of Rheumatology in Immuno-Oncology.Cancer Immunology, Immunotherapy. 2021; 70: 2197-2207
- Predictors of immunotherapy-induced immune-related adverse events.Current Oncology. 2018; 25: 403-410
- Immune-related adverse events in cancer patients treated with immune checkpoint inhibitors: A single-center experience.Medicine. 2019; 98
- Pre-existing autoimmune disease and the risk of immune-related adverse events among patients receiving checkpoint inhibitors for cancer.Cancer Immunology, Immunotherapy. 2019; 68: 917-926
- Musculoskeletal rheumatic complications of immune checkpoint inhibitor therapy: a single center experience.in: Paper presented at: Seminars in arthritis and rheumatism. 2019
- Endocrine toxicity in cancer patients treated with nivolumab or pembrolizumab: results of a large multicentre study.Journal of endocrinological investigation. 2020; 43: 337-345
- Safety of immune checkpoint blockade in patients with cancer and preexisting autoimmune diseases and/or chronic inflammatory disorders.Journal of Immunotherapy and Precision Oncology. 2019; 2: 59-64
- Safety and efficacy of immune checkpoint inhibitors in patients with cancer and preexisting autoimmune disease: a nationwide, multicenter cohort study.Arthritis & rheumatology. 2019; 71: 2100-2111
- Safety and clinical outcomes of immune checkpoint inhibitors in patients with cancer and preexisting autoimmune diseases.Journal of Immunotherapy. 2021; 44: 362-370
- Real-world outcomes and clinical predictors of immune checkpoint inhibitor monotherapy in advanced lung cancer.Clinical Medicine Insights: Oncology. 2021; 1511795549211004489
- Immunotherapy to treat malignancy in patients with pre-existing autoimmunity.Journal for immunotherapy of cancer. 2020; 8
- Preexisting autoimmune disease: implications for immune checkpoint inhibitor therapy in solid tumors.Journal of the National Comprehensive Cancer Network. 2019; 17: 750-757
- Immunotherapy in patients with autoimmune disease.Journal of Thoracic Disease. 2020; 12: 7032
- Safety profiles of anti-CTLA-4 and anti-PD-1 antibodies alone and in combination.Nature reviews Clinical oncology. 2016; 13: 473-486
- Advanced Materials for Management of Immune-Related Adverse Events Induced by Immune Checkpoint Inhibitors.Materials & Design. 2022; 110738
- Immune-related adverse events and the balancing act of immunotherapy.Nature communications. 2022; 13: 1-4
- Association of immune-related adverse events with nivolumab efficacy in non–small-cell lung cancer.JAMA oncology. 2018; 4: 374-378
- Correlation between immune-related adverse events and efficacy in non-small cell lung cancer treated with nivolumab.Lung Cancer. 2018; 115: 71-74
- Association of immune-related adverse events with clinical benefit in patients with advanced non-small-cell lung cancer treated with nivolumab.The oncologist. 2018; 23: 1358-1365
- Immune-related adverse events and survival in solid tumors treated with immune checkpoint inhibitors: a systematic review and meta-analysis.Journal of Immunotherapy. 2020; 43: 1-7
- Immune-related adverse events and anti-tumor efficacy of immune checkpoint inhibitors.Journal for immunotherapy of cancer. 2019; 7: 1-11
- Comprehensive analysis of the characteristics and treatment outcomes of patients with non-small cell lung cancer treated with anti-PD-1 therapy in real-world practice.Journal of cancer research and clinical oncology. 2019; 145: 1613-1623
- Efficacy and safety of immune checkpoint inhibitors in patients with advanced non–small cell lung cancer (NSCLC): a systematic literature review.Oncoimmunology. 2020; 91774314
- Grade 3–4 Immune-Related Adverse Events Induced by Immune Checkpoint Inhibitors in Non-Small-Cell Lung Cancer (NSCLC) Patients Are Correlated with Better Outcome: A Real-Life Observational Study.Cancers. 2022; 14: 3878
Article info
Publication history
Accepted:
May 22,
2023
Received in revised form:
May 21,
2023
Received:
March 24,
2023
Publication stage
In Press Journal Pre-ProofFootnotes
PROSPERO Registration Number: CRD42022311081
Identification
Copyright
© 2023 Elsevier Inc. All rights reserved.
