Preexisting immune‐mediated inflammatory disease is associated with improved survival and increased toxicity in melanoma patients who receive immune checkpoint inhibitors

Gulati, Nicholas; Celen, Arda; Johannet, Paul; Mehnert, Janice M.; Weber, Jeffrey S.; Krogsgaard, Michelle; Osman, Iman; Zhong, Judy

doi:10.1002/cam4.4239

Cited by 16 publications

(12 citation statements)

References 30 publications

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“…Among these, three studies were from Japan, 20 , 21 , 24 one from Korea, 28 two from Italy, 22 , 32 one from France, 25 two from Germany, 26 , 33 one from the UK, 29 one from Switzerland, 23 one from Holland, 27 and two from the US. 34 , 35 Nine studies reported on non-small cell lung cancer (NSCLC), 20–22 – 24 , 25-28 – 29-33 – 35 seven on melanoma, 22–25 – 27–32 – 34 , 35 and three on metastatic renal cell cancer and urothelial carcinomas. 22 , 23 , 35 Among AIDs, ILD and endocrine AID were most frequently mentioned.…”

Section: Resultsmentioning

confidence: 99%

“…R software (version 4.1.3) was used for data analyses. RR was used to re ect the incidence of irAEs of any grade and grade ≥ 3 [15][16][17][18][19][20][21] . If the studies recorded HR for PFS or OS, we adopted the results.…”

Section: Discussionmentioning

confidence: 99%

“…Among these, three studies were from Japan [15,16,22] , one from Korea [17] , two from the Italy [18,25] , one from Germany [26] , one from the UK [19] , one from Switzerland [20] , one from Holland [27] , and one from the US [21] . Seven studies focused on non-small cell lung cancer [15-17, 19, 22, 26] , four reported melanoma [18,21,25,27] , and two involved in metastatic renal cell cancer and urothelial carcinoma [18,20] . Among AIDs, pneumonic AID and endocrine AID were the most frequently mentioned.…”

Section: Characteristics Of the Selected Studiesmentioning

confidence: 99%

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Safety and efficacy of immune checkpoint inhibitors in advanced cancer patients with autoimmune disease: A meta-analysis

Cai

Huo

Zhu

et al. 2022

Human Vaccines & Immunotherapeutics

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Background: Cancer patients with autoimmune disease (AID) are usually excluded from clinical trials involving immune checkpoint inhibitors (ICIs); their safety and effectiveness remain uncertainty.Methods: The available electronic databases were systematically searched. We recorded the incidence of immune-related adverse events (irAEs), progression-free survival (PFS), and overall survival (OS) of included studies.Results: This meta-analysis included 11 studies comprising 5489 participants. The pooled risk ratio (RR) for any grade and grade ≥3 irAEs was 1.79 (95% con dence interval [CI]: 1.31-2.45) and 1.58 (95% CI: 1.06-2.36), respectively. The irAEs in the same system as the AID were referred to as AID-homogeneous irAEs, otherwise known as AID-heterogeneous irAEs. Subgroup analysis found that the higher risk of AID-homogeneous irAEs contributed to the higher risk of overall irAEs among patients with AID. The pooled hazard ratio (HR) for PFS and OS was 1.09 (95% CI: 0.96-1.25) and 1.10 (95% CI: 0.68-1.77), respectively. The results of PFS and OS subgroup analyses matched the overall results.Conclusion: patients with AID had a signi cantly higher risk of developing any grade and ≥3 grade irAEs under ICI therapy, speci cally AIDhomogeneous irAEs; however, AID-heterogeneous irAEs were higher among patients with AID than in those without. No statistically signi cant differences in PFS and OS were observed between two groups.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Characteristics Of the Selected Studiesmentioning

confidence: 99%

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Safety and efficacy of immune checkpoint inhibitors in advanced cancer patients with autoimmune disease: A meta-analysis

Cai

Huo

Zhu

et al. 2022

Human Vaccines & Immunotherapeutics

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“…The most frequent ADs were rheumatoid arthritis (5.9%), psoriasis (2.8%), polymyalgia rheumatica (1.8%), Addison disease (1%), systemic lupus erythematosus (0.9%), ulcerative colitis (0.8%), giant cell arteritis (0.8%), sicca syndrome (0.6%), regional enteritis (0.5%), and Ménière disease (0.5%) (Khan et al 2016). A study by Gulati et al (Gulati et al 2021) showed that female patients with melanoma and a pre-existing AD who received ICI therapy had improved overall survival. This evidence shows the importance of better understanding the usefulness of ICI therapy in patients with pre-existing ADs.…”

Section: Discussionmentioning

confidence: 98%

Immune-related adverse events after immune checkpoint inhibitor exposure in adult cancer patients with pre-existing autoimmune diseases

Machado

Shatila

Liu

et al. 2023

J Cancer Res Clin Oncol

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Immune checkpoint inhibitor (ICI) therapy can predispose patients to immune-related adverse events (irAEs) and autoimmune disease (AD) are-ups, but the characteristics of irAEs among patients with pre-existing ADs are largely unknown. We conducted this study to determine the clinical courses, irAEs, AD ares, treatment, and outcomes of patients with AD on ICIs. MethodsThis was a retrospective study of adult cancer patients at a large cancer center who were diagnosed with ADs before undergoing ICI therapy. Patients' clinical courses, complications, treatments, and outcomes related to both ADs ares and irAEs were collected and analyzed. ResultsThe study included 197 patients. Most (55.4%) were women. Melanoma comprised the highest proportion (28.4%) of malignancies, and most (83.8%) patients received PD-1/PD-L1 inhibitors. Fifty (25.3%) patients developed a new irAE after starting ICI therapy, while 29 (14.7%) patients had an AD are-up. Patients with in ammatory bowel disease had the highest incidence of AD are-ups (31.7%), while patients with Hashimoto hypothyroidism had the highest incidence of new irAEs (39.2%). Patients with in ammatory bowel disease had more severe adverse events. In our cohort, patients with a new diagnosis of irAE were treated with immunosuppressive therapy. AD ares were managed similarly. With regard to irAE manifestations, the most common presentations were colitis (24 [12.1%] patients), hepatic transaminase elevations (8 [4%] patients), and pneumonitis (7 [3.5%] patients). ConclusionOur ndings suggest that patients with gastrointestinal and rheumatologic ADs had a higher incidence of AD are-ups, while patients with Hashimoto hypothyroidism and neurologic ADs had a higher incidence of new irAEs. Patients with prior ADs experiencing are-ups or new irAEs after ICI therapy tend to require aggressive immunosuppressive treatment. Thorough evaluation of baseline disease status, appropriate medical management before ICI therapy, and early recognition of in ammatory exacerbation may help ensure long-term success in treating and improving outcomes in these patients. This retrospective chart review was a descriptive, single-center study that included patients aged 18 years or older who had cancer and who received ICI therapy at The University of Texas MD Anderson Cancer Center from 10/01/2014 to 04/30/2021. All patients included in the study had a con rmed AD diagnosis before the start of ICI therapy (Fig. 1). We identi ed patients aged 18 years or older who (1) were treated with ICI for various types of cancer and (2) had a diagnosis of autoimmune disease prior to the rst base on the past medical history on the study entry note before starting ICI. Patients excluded (1) were patients aged less than 18 years old and (2) did not have a past medical history of AD (Fig. 1). This study was approved by the Institutional Review Board with a waiver of patients' informed consent. Clinical dataFrom the patients' electronic medical records, we extracted demographic and cancer-related information, such as patie...

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“…IRAEs are practically similar to the condition from clinically significant inflammatory toxicities. It is well known that the immune-mediated inflammatory disorders are considered relative contraindication to the novel immune therapy due to the risk of provoking flares [ 51 ]. In this context, appropriate gut-directed interventions such as diet, nutritional supplementation, and/or fecal transplantation could calm down the inflammatory response and/or improve the course of immune-mediated inflammatory disorders [ 52 ].…”

Section: Innovative Praxis With Gut-brain-immune Axis For the Potenti...mentioning

confidence: 99%

Encouraging probiotics for the prevention and treatment of immune-related adverse events in novel immunotherapies against malignant glioma

Yoshikawa

Taniguchi

Sawamura

et al. 2022

Exploration of Targeted Anti-Tumor Therapy

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Among the malignant tumors in the central nervous system (CNS), glioma is the most challenging tumor to the public society, which accounts for the majority of intracranial malignant tumors with impaired brain function. In general, conventional therapies are still unable to provide an effective cure. However, novel immunotherapies have changed the treatment scene giving patients a greater potential to attain long term survival, improved quality of life. Having shown favorable results in solid tumors, those therapies are now at a cancer research hotspot, which could even shrink the growth of glioma cells without causing severe complications. However, it is important to recognize that the therapy may be occasionally associated with noteworthy adverse action called immune-related adverse events (IRAEs) which have emerged as a potential limitation of the therapy. Multiple classes of mediators have been developed to enhance the ability of immune system to target malignant tumors including glioma but may also be associated with the IRAEs. In addition, it is probable that it would take long time after the therapy to exhibit severe immune-related disorders. Gut microbiota could play an integral role in optimal immune development and/or appropriate function for the cancer therapy, which is a vital component of the multidirectional communication between immune system, brain, and gut, also known as gut-brain-immune axis. Here, we show the potential effects of the gut-brain-immune axis based on an “engram theory” for the innovative treatment of IRAEs.

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Preexisting immune‐mediated inflammatory disease is associated with improved survival and increased toxicity in melanoma patients who receive immune checkpoint inhibitors

Abstract: This is an open access article under the terms of the Creat ive Commo ns Attri bution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 16 publications

References 30 publications

Safety and efficacy of immune checkpoint inhibitors in advanced cancer patients with autoimmune disease: A meta-analysis

Safety and efficacy of immune checkpoint inhibitors in advanced cancer patients with autoimmune disease: A meta-analysis

Immune-related adverse events after immune checkpoint inhibitor exposure in adult cancer patients with pre-existing autoimmune diseases

Encouraging probiotics for the prevention and treatment of immune-related adverse events in novel immunotherapies against malignant glioma

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