Immunotherapy to treat malignancy in patients with pre-existing autoimmunity

Boland, Patrick M.; Pavlick, Anna C.; Weber, Jeffrey S.; Sandigursky, Sabina

doi:10.1136/jitc-2019-000356

Cited by 40 publications

(30 citation statements)

References 67 publications

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“…The current study did not analyze the impact of autoimmune diseases as preexisting autoimmunity may be associated with ICIs efficacy and irAE [38]. However, the previous studies showed ICIs lead to similar rates of irAEs in patients with coexisting autoimmune diseases compared with those without existing coexisting autoimmune diseases [39].…”

Section: Discussionmentioning

confidence: 86%

The association between immune-related adverse events and survival outcomes in Asian patients with advanced melanoma receiving anti-PD-1 antibodies

Yang

Peng

et al. 2020

BMC Cancer

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Background The association between immune-related adverse events (irAEs) and survival outcomes in patients with advanced melanoma receiving therapy with immune checkpoint inhibitors (ICIs) has not been well established, particularly in Asian melanoma. Methods We retrospectively reviewed 49 melanoma patients undergoing therapy with ICIs (anti-PD-1 monotherapy), and analyzed the correlation between irAEs and clinical outcomes including progression-free survival (PFS) and overall survival (OS). Results: Overall, the patients who experienced grade 1–2 irAEs had longer PFS (median PFS, 4.6 vs. 2.5 months; HR, 0.52; 95% CI: 0.27–0.98; p = 0.042) and OS (median OS, 15.2 vs. 5.7 months; HR, 0.50; 95% CI: 0.24–1.02; p = 0.058) than the patients who did not experience irAEs. Regarding the type of irAE, the patients with either skin/vitiligo or endocrine irAEs showed better PFS (median PFS, 6.1 vs. 2.7 months; HR, 0.40, 95% CI: 0.21–0.74; p = 0.003) and OS (median OS, 18.7 vs. 4.5 months; HR, 0.34, 95% CI: 0.17–0.69, p = 0.003) than patients without any of these irAEs. Conclusions Melanoma patients undergoing anti-PD-1 monotherapy and experiencing mild-to-moderate irAEs (grade 1–2), particularly skin (vitiligo)/endocrine irAEs had favorable survival outcomes. Therefore, the association between irAEs and the clinical outcomes in melanoma patients undergoing anti-PD-1 ICIs may be severity and type dependent.

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Section: Discussionmentioning

confidence: 86%

The association between immune-related adverse events and survival outcomes in Asian patients with advanced melanoma receiving anti-PD-1 antibodies

Yang

Peng

et al. 2020

BMC Cancer

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“…In breast cancer, a lower rate of systemic treatment was seen in rural areas [ 54 , 55 ]. Flare of a pre-existing autoimmune disorder is common with ICI treatment [ 56 , 57 , 58 ], but information on patients with autoimmune disorder receiving ICI is only available from retrospective studies, as patients were excluded from clinical trials [ 56 ]. Additionally, in most studies heterogenous autoimmune disorders were summarized.…”

Section: Discussionmentioning

confidence: 99%

Factors Influencing the Adjuvant Therapy Decision: Results of a Real-World Multicenter Data Analysis of 904 Melanoma Patients

Lodde

Forschner

Hassel

et al. 2021

Cancers

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Adjuvant treatment of melanoma patients with immune-checkpoint inhibition (ICI) and targeted therapy (TT) significantly improved recurrence-free survival. This study investigates the real-world situation of 904 patients from 13 German skin cancer centers with an indication for adjuvant treatment since the approval of adjuvant ICI and TT. From adjusted log-binomial regression models, we estimated relative risks for associations between various influence factors and treatment decisions (adjuvant therapy yes/no, TT vs. ICI in BRAF mutant patients). Of these patients, 76.9% (95% CI 74–80) opted for a systemic adjuvant treatment. The probability of starting an adjuvant treatment was 26% lower in patients >65 years (RR 0.74, 95% CI 68–80). The most common reasons against adjuvant treatment given by patients were age (29.4%, 95% CI 24–38), and fear of adverse events (21.1%, 95% CI 16–28) and impaired quality of life (11.9%, 95% CI 7–16). Of all BRAF-mutated patients who opted for adjuvant treatment, 52.9% (95% CI 47–59) decided for ICI. Treatment decision for TT or ICI was barely associated with age, gender and tumor stage, but with comorbidities and affiliated center. Shortly after their approval, adjuvant treatments have been well accepted by physicians and patients. Age plays a decisive role in the decision for adjuvant treatment, while pre-existing autoimmune disease and regional differences influence the choice between TT or ICI.

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“…Due to the fact that patients with preexisting autoimmune diseases had a higher frequency of severe irAEs and new disease symptoms, for some time there were restrictions on the inclusion of these patients in treatment groups [ 121 ]. However, recent retrospective data have demonstrated the safety and efficacy of ICIs in patients with pre-existing AID [ 122 ]. The presence of AID in the anamnesis requires more careful monitoring of the patient’s condition, and the management with specialists in autoimmune pathologies.…”

Section: Classical Examples Of the Asia Syndromementioning

confidence: 99%

Classical Examples of the Concept of the ASIA Syndrome

et al. 2020

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Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) was first introduced in 2011 by Shoenfeld et al. and encompasses a cluster of related immune mediated diseases, which develop among genetically prone individuals as a result of adjuvant agent exposure. Since the recognition of ASIA syndrome, more than 4400 documented cases have been reported so far, illustrated by heterogeneous clinical manifestations and severity. In this review, five enigmatic conditions, including sarcoidosis, Sjögren’s syndrome, undifferentiated connective tissue disease, silicone implant incompatibility syndrome (SIIS), and immune-related adverse events (irAEs), are defined as classical examples of ASIA. Certainly, these disorders have been described after an adjuvant stimulus (silicone implantation, drugs, infections, metals, vaccines, etc.) among genetically predisposed individuals (mainly the HLA-DRB1 and PTPN22 gene), which induce an hyperstimulation of the immune system resulting in the production of autoantibodies, eventually leading to the development of autoimmune diseases. Circulating autonomic autoantibodies in the sera of patients with silicone breast implants, as well as anatomopathological aspects of small fiber neuropathy in their skin biopsies have been recently described. To our knowledge, these novel insights serve as a common explanation to the non-specific clinical manifestations reported in patients with ASIA, leading to the redefinition of the ASIA syndrome diagnostic criteria.

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Immunotherapy to treat malignancy in patients with pre-existing autoimmunity

Cited by 40 publications

References 67 publications

The association between immune-related adverse events and survival outcomes in Asian patients with advanced melanoma receiving anti-PD-1 antibodies

The association between immune-related adverse events and survival outcomes in Asian patients with advanced melanoma receiving anti-PD-1 antibodies

Factors Influencing the Adjuvant Therapy Decision: Results of a Real-World Multicenter Data Analysis of 904 Melanoma Patients

Classical Examples of the Concept of the ASIA Syndrome

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