Immune-Related Adverse Events as a Biomarker in Non-Melanoma Patients Treated with Programmed Cell Death 1 Inhibitors

Judd, Joseph T.; Zibelman, Matthew R.; Handorf, Elizabeth A.; O’Neill, John P.; Ramamurthy, Chethan; Bentota, Sasini; Doyle, Jamie Mihoko; Uzzo, Robert G.; Bauman, Jessica R.; Borghaei, Hossein; Plimack, Elizabeth R.; Mehra, Ranee; Geynisman, Daniel M.

doi:10.1634/theoncologist.2017-0133

Cited by 119 publications

(96 citation statements)

References 28 publications

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“…Recent reports have suggested a correlation between the development of irAEs and the clinical efficacy of ICIs in various types of cancer. 10,11 In advanced NSCLC patients, two prospective studies revealed that irAEs patients had a significantly higher ORR and longer PFS than non-irAEs patients. 12,13 Immune-related thyroid dysfunction was significantly correlated with a longer OS.…”

Section: Discussionmentioning

confidence: 99%

Immune checkpoint inhibitor‐associated interstitial lung diseases correlate with better prognosis in patients with advanced non‐small‐cell lung cancer

et al. 2020

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Background Interstitial lung disease (ILD) induced by immune checkpoint inhibitors (ICIs) is a potentially life‐threatening adverse event. The purpose of this study was to evaluate whether the development of immune‐related adverse events (irAEs), especially ILD, was associated with treatment efficacy and to research the features and risk factors of ILD in advanced non‐small cell lung cancer (NSCLC). Methods Between December 2015 and November 2018, 130 advanced NSCLC patients were treated with nivolumab, pembrolizumab or atezolizumab. The patients were categorized into two groups (irAEs group or non‐irAEs group). Subsequently, we divided the irAEs group into two groups based on the incidence of ILD (ILD group and irAEs‐non‐ILD group). Treatment efficacy and the characteristics of ILD were evaluated. Results A total of 39 (30%) patients developed irAEs. ILD was observed in 16 (12%) patients. Patients with ILD had a higher objective response rate (ORR) compared with irAEs‐non‐ILD patients and non‐irAEs patients (63%, 43% and 22%, respectively). Median progression‐free survival (mPFS) was 15.9 months in ILD patients, 5.4 months in irAEs‐non‐ILD patients and 3.3 months in non‐irAEs patients (log‐rank test, P = 0.033). Pre‐existing interstitial pneumonia (IP) was an independent risk factor for ILD‐induced ICIs (odds ratio [OR] 14.7; 95% confidence interval [CI]: 2.16–99.6, P = 0.006). Conclusions ORR and PFS were significantly better in ILD patients than in irAEs‐non‐ILD and non‐irAEs patients. Pre‐existing history of IP was an independent risk factor for ILD‐induced ICIs.

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Section: Discussionmentioning

confidence: 99%

Immune checkpoint inhibitor‐associated interstitial lung diseases correlate with better prognosis in patients with advanced non‐small‐cell lung cancer

et al. 2020

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“…In all cases of necrotizing vasculitis and systemic sclerosis, skin biopsy supported the clinical diagnosis. Three patients had flares of preexisting inflammatory arthritis: 2 with RA and 1 with Sjögren's syndrome (patients [15][16][17]. None of these patients had clinically active disease at the time of ICI initiation.…”

Section: Inflammatory Arthritis Thirty-four Patients Treated Withmentioning

confidence: 99%

Rheumatic Syndromes Associated With Immune Checkpoint Inhibitors: A Single‐Center Cohort of Sixty‐One Patients

Richter

Crowson

Kottschade

et al. 2019

Arthritis & Rheumatology

118

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Objective To describe the prevalence, clinical presentation, and management of rheumatic immune‐related adverse effects (Rh‐irAEs) from immune checkpoint inhibitor (ICI) therapy. Methods From a database of all patients who received any ICI at the Mayo Clinic Rochester, Minnesota campus between January 1, 2011 and March 1, 2018, we retrospectively identified those with Rh‐irAEs, using diagnostic codes, search terms, and manual chart review. Results Of the 1,293 patients who received any ICI, Rh‐irAEs were clinically diagnosed in 43. Eighteen patients with Rh‐irAEs who received ICI therapy elsewhere were also analyzed. Clinical syndromes included inflammatory arthritis (n = 34 [prevalence 2%]), myopathy (n = 10), and other rheumatic syndromes (n = 17). Inflammatory arthritis was most commonly polyarticular, and glucocorticoid treatment was required in 26 patients (76%). The mean ± SD duration of treatment was 18 ± 18 weeks. Five patients (15%) also received disease‐modifying antirheumatic drugs, and ICI therapy had to be discontinued in 3 patients (9%). Myopathy was treated with glucocorticoids in all cases (mean ± SD treatment duration 15 ± 17 weeks) and led to 2 deaths and permanent ICI discontinuation in 9 patients (90%). Other syndromes included connective tissue diseases, vasculitis, polymyalgia rheumatica–like syndrome, and flare of preexisting rheumatic disease. Most (71%) were treated with immunosuppression, with 12% requiring ICI discontinuation. Conclusion This study represents the largest cohort of patients with Rh‐irAEs reported to date. Most patients received long courses of immunosuppressive treatment, although discontinuation of ICI therapy was required in only a minority.

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“…Certain dermatologic irAEs such as vitiligo may be irreversible, and patients should be informed about the associated risk prior to initiating ICIs. Emerging data suggest that the development of irAEs is associated with objective tumor responses and improved survival outcomes . It is therefore imperative that we treat irAEs effectively while minimizing interruption of therapy with ICIs, because patients who develop irAEs appear to be more likely to derive benefit from continued treatment.…”

Section: Implications For Clinical Practicementioning

confidence: 99%

Cases from the irAE Tumor Board: A Multidisciplinary Approach to a Patient Treated with Immune Checkpoint Blockade Who Presented with a New Rash

et al. 2018

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Immune checkpoint inhibitors (ICIs) have revolutionized the treatment paradigms for a broad spectrum of malignancies. Because immune checkpoint inhibitors rely on immune reactivation to eliminate cancer cells, they can also lead to the loss of immune tolerance and result in a wide range of phenomena called immune‐related adverse events (irAEs). At our institution, the management of irAEs is based on multidisciplinary input obtained at an irAE tumor board that facilitates expedited opinions from various specialties and allows for a more uniform approach to these patients. In this article, we describe a case of a patient with metastatic urothelial carcinoma who developed a maculopapular rash while being treated with a programmed death‐ligand 1 inhibitor. We then describe the approach to management of dermatologic toxicities with ICIs based on the discussion at our irAE Tumor Board. Key Points Innocuous symptoms such as pruritis or a maculopapular rash may herald potentially fatal severe cutaneous adverse reactions (SCARs); therefore, close attention must be paid to the symptoms, history, and physical examination of all patients. Consultation with dermatology should be sought for patients with grade 3 or 4 toxicity or SCARs and prior to resumption of immune checkpoint inhibitors for patients with grade 3 or higher toxicity. A multidisciplinary immune‐related adverse events (irAE) tumor board can facilitate timely input and expertise from various specialties, thereby ensuring a streamlined approach to management of irAEs.

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Immune-Related Adverse Events as a Biomarker in Non-Melanoma Patients Treated with Programmed Cell Death 1 Inhibitors

Cited by 119 publications

References 28 publications

Immune checkpoint inhibitor‐associated interstitial lung diseases correlate with better prognosis in patients with advanced non‐small‐cell lung cancer

Immune checkpoint inhibitor‐associated interstitial lung diseases correlate with better prognosis in patients with advanced non‐small‐cell lung cancer

Rheumatic Syndromes Associated With Immune Checkpoint Inhibitors: A Single‐Center Cohort of Sixty‐One Patients

Cases from the irAE Tumor Board: A Multidisciplinary Approach to a Patient Treated with Immune Checkpoint Blockade Who Presented with a New Rash

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