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Displaying One Session

PARALLEL SESSIONS
Session Type
PARALLEL SESSIONS
Session Time
13:30 - 15:30
Session Icon
Pre Recorded

CHECK POINT INHIBITORS INDUCED AUTOIMMUNITY

Session Type
PARALLEL SESSIONS
Date
29.05.2021, Saturday
Session Time
13:30 - 15:30
Room
HALL B
Lecture Time
13:30 - 13:50
Session Icon
Pre Recorded

ISOLATED AUTOIMMUNE ADRENOCORTICOTROPHIC HORMONE DEFICIENCY: FROM A RARE DISEASE TO THE DOMINANT CAUSE OF ADRENAL INSUFFICIENCY RELATED TO IMMUNE CHECK POINT INHIBITORS

Session Type
PARALLEL SESSIONS
Date
29.05.2021, Saturday
Session Time
13:30 - 15:30
Room
HALL B
Lecture Time
13:50 - 14:10
Session Icon
Pre Recorded

Abstract

Background and Aims

Immune checkpoint inhibitors have introduced a new and heterogeneous class of immune-related adverse effects, with the endocrine system being a predominant target for autoimmunity. Autoimmune hypothalamic-pituitary-adrenal (HPA) axis diseases induced by checkpoint inhibitors are being increasingly recognized. We aimed to characterize the spectrum of HPA axis endocrinopathies.

Methods

A retrospective cohort study all patients who received immunotherapy (Ipilimumab, Nivolumab, Pembrolizumab, Atezolizumab, Avelumab and/or Durvalumab) between January 2015 and October 2018 in a large tertiary cancer center. Patients were characterized for HPA axis abnormalities based on clinical and pituitary axes evaluation. The risk for developing HPA endocrinopathies was compared by log- rank test, by the time since checkpoint inhibitors initiation. Additionally, the risk for developing HPA endocrinopathies after adjusting for covariates was assessed using multivariable logistic regression analysis.

Results

Among 1615 patients, fourteen (0.87%) patients developed isolated adrecocorticotrophic hormone deficiency (IAD), six (0.37%) - hypophysitis and no case of adrenalitis was identified. IAD presented with mild and non-specific symptoms, mainly asthenia. In multivariable analysis, exposure to both PD-1/PD-L1 and Ipilimumab and female gender were associated with an increased odds ratio (OR) for developing IAD (6.98 [95% CI 2.38-20.47, p<0.001] and 3.67 [95% CI 1.13-11.84, p=0.03]), respectively.

Conclusions

Isolated ACTH Deficiencty, a rare disease before the immunotherapy era, has become a predominant checkpoint related HPA axis autoimmune injury. Despite its life threatening potential, IAD may be missed due to its subtle presentation. Patients exposed to Ipilimumab and PD-1/PD-L1 in combination or sequentially and women have an increased risk for developing IAD.

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ANTI PD-L1 TREATMENT SKEWS PAROTID SALIVARY GLAND EPITHELIAL CELL COMPOSITION.

Session Type
PARALLEL SESSIONS
Date
29.05.2021, Saturday
Session Time
13:30 - 15:30
Room
HALL B
Lecture Time
14:10 - 14:20
Session Icon
Pre Recorded

Abstract

Background and Aims

Background

The salivary glands (SGs) can be (severely) damaged by immune checkpoint inhibitor (ICI) therapy. In patients with ICI-induced SG dysfunction, 60% progress to fulfill classification criteria for primary Sjögren’s syndrome (pSS), owing to immune foci in SGs, and/or anti-SSA autoantibody positivity. Here we aim to understand how ICI treatment affects the SG epithelium.

Methods

Methods

Immunohistochemistry for CD4, CD8, cytokeratin 7 (CK7), AQP5, Ki67 and PD-L1 was performed in a parotid SG biopsy from a patient treated with anti-PD-L1, a control and a pSS patient.

Results

Results

Following PD-L1 blockade, dispersed and focal CD4+ T cell-rich infiltrate was observed. CD8+ T cells were also present. In this patient, no classical AQP5+ CK7- acinar cell clusters were observed (CK7 marks intercalated ducts, IDs). The parenchyma was dominated by aberrant epithelial ‘structures’ with ID-like morphology, containing a mixture of AQP5+CK7-, AQP5-CK7+ and AQP5+CK7+ cells (30 structures/mm2, 2/mm2 in control, 10/mm2 in pSS; Figure 1). 130 Ki67+ proliferating cells/mm2 in these epithelial structures were detected post-PD-L1 blockade (5/mm2 in control and 16/mm2 in pSS acinar+ID compartment). CD4+ and CD8+ T cells were observed in-between and inside aberrant structures following post-PD-L1 blockade. Immunostaining revealed that acinar cells in healthy SGs express PD-L1, suggesting an ability to interact directly with anti PD-L1 ICIs.

figure 1_pd-l1.jpg

Conclusions

Conclusions

We show in this case study dramatically altered SG epithelium following anti-PD-L1 therapy, specifically presence of aberrant intercalated duct-like structures. The mechanism behind this dysfunction remains to be elucidated, and will be critical to understand checkpoint inhibitor induced development of sicca complaints.

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PD(L)-1 INHIBITORS DO NOT ONLY EXACERBATE, BUT ALSO CAUSE DE NOVO PSORIASIS

Session Type
PARALLEL SESSIONS
Date
29.05.2021, Saturday
Session Time
13:30 - 15:30
Room
HALL B
Lecture Time
14:20 - 14:30
Session Icon
Pre Recorded

Abstract

Background and Aims

Introduction

Immune checkpoints such as PD-1 and PDL-1 inhibitors ensure the immunologic homeostasis by blocking excessive T cell activation. Tumors also use these checkpoints to evade recognition by the immune system. In recent years, immune checkpoint blockade has shown to have a potent anti-tumor effect, by shifting the immune system towards anti-tumor activity. Due to their specific mechanism of action, immune checkpoint inhibitors have specific immune-related adverse events. The most frequent irAEs are cutaneous.

Methods

Several cases of psoriasis induced by PD(L)-1 inhibitors:

A 75-year old woman with renal cell carcinoma presented with a psoriasis exacerbation after one month of Nivolumab. A 59-year old man with Non-Small Cell Lung Cancer developed a de novo psoriasis after one month of Nivolumab. A 30-year old man developed a de novo psoriasis guttata after one year of Nivolumab. A 67-year old man was treated with pembrolizumab and developed a de novo psoriasis guttata after two months. A 59-year old man was treated with avelumab for a glioblastoma and developed a psoriasis exacerbation after three months.

Results

Discussion:

While psoriasis exacerbation during immune checkpoint blockade is a well-described irAE, development of de novo psoriasis is less frequently observed. Pathogenesis is poorly understood, but it has been shown that the Th1/Th17 pathway is upregulated. Treating the psoriasis can be challenging, since the use of immunosuppressive treatment is fairly restricted because of the concomitant cancer. The development of psoriasis however should usually never be the sole reason to stop the checkpoint inhibitor.

Conclusions

See discussion

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MYOSITIS ASSOCIATED WITH IMMUNE CHECKPOINT INHIBITORS: DISPROPORTIONALITY ANALYSES USING THE WORLD HEALTH ORGANIZATION’S ADVERSE DRUG REACTIONS DATABASE.

Session Type
PARALLEL SESSIONS
Date
29.05.2021, Saturday
Session Time
13:30 - 15:30
Room
HALL B
Lecture Time
14:30 - 14:40
Session Icon
Pre Recorded

Abstract

Background and Aims

The increasing use of immune checkpoint inhibitors (ICIs) for curing cancer results in a wide range of novel immune related adverse events (irAEs). Among them, myositis is a rare but potentially life-threatening event.

This study aimed at investigating the risk of ICI-related myositis in real-life settingby performing a disproportionality analysis in a global pharmacovigilance database.

Methods

We conducted a case/non-case analysis using VigiBase, the WHO’s adverse drug reactions (ADRs) database, to assess myositis reporting associated with anti-PD-1 (nivolumab, pembrolizumab), anti-PD-L1 (atezolizumab, avelumab, durvalumab), anti-CTLA-4 (ipilimumab, tremelimumab). Cases were defined using selected MedDRA Low Level Terms corresponding to myositis and non-cases were all other ADR. Disproportionality analysis were performed using logistic regression models to calculate Reporting Odds Ratios (ROR).

Results

A total of 14,786,263ADR were reported from January 2008 to February 2019. We identified 54,085 ICI-related ADR among which 345 myositis. ICI-related myositis was considered serious in 95% of cases, with fatal outcome in more than 20%. Association with myocarditis and myasthenia gravis was reported in 11,3% and 11,9% of cases respectively. Myositis was more than seventeen times more reported with ICI agents than with all other drugs (ROR=17.3; 95%CI:15.5–19.2). ICI-related myositis reporting was increased with anti-PD-(L)1 compared to anti-CTLA-4 agents (ROR=2.4; 95%CI:1.6–3.5), and in the group receiving combination-therapy compared to monotherapy (ROR 1.8; 95%CI: 1.3–2.4).

Conclusions

Such a strong pharmacovigilance signal suggests an increased risk of myositis under ICIs, even more increased under anti-PD(L)1 agents. Subsequent studies are required to better characterize clinical features of ICI-related myositis.

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NEUROLOGIC ADVERSE EVENTS OF IMMUNE CHECKPOINT INHIBITORS AND ANTIBODIES AGAINST NEURAL ANTIGENS.

Session Type
PARALLEL SESSIONS
Date
29.05.2021, Saturday
Session Time
13:30 - 15:30
Room
HALL B
Lecture Time
14:40 - 14:50
Session Icon
Pre Recorded

Abstract

Background and Aims

Neurological immune-related adverse events (N-irAEs) with varying frequency and severity have been reported in patients with cancer treated with immune-checkpoint-inhibitors (ICIs). Severe N-irAEs can be similar to paraneoplastic neurological syndromes, but their association with antineuronal antibodies is not well known.

To describe the neurological AEs after ICIs treatment, the frequency of antineuronal and glial antibodies and its clinical implication.

Methods

Case series studied in the laboratory of Hospital Clínic-IDIBAPS between Jan ‘18 and Oct ‘19. Onconeural, neuronal surface and glial antibody detection by rat brain immunohistochemistry, and confirmatory cell/immunoblot assays. Review of clinical features, type of cancer, ICI treatment and outcome.

Results

18 patients were referred from 10 different hospitals for antibody studies. 12 (67%) were men; median age 61.5 years (range 41-82). 12 (67%) had lung cancer, 3 melanoma, 1 prostate, 1 breast and 1 Hodgkin lymphoma. 6 (33%) patients received nivolumab, 5 (28%) pembrolizumab, 4 (22%) nivolumab + ipilimumab, 2 durvalumab and 1 atezolizumab. The clinical presentation was encephalitis/encephalopathy in 12 (67%), visual disturbances 2, encephalomyelitis 1, cerebellar ataxia 1, meningitis 1 and intestinal pseudo-obstruction 1. Anti-neural antibodies were detected in 5 (28%) patients: 1 anti-GABABR, 1 anti-Hu, 1 anti-Ma2 and 2 anti-GFAP. In 2 patients the antibodies were present before ICI initiation. The majority of cases received treatment with corticosteroids, with improvement of neurological symptoms.

Conclusions

Nearly 30% of patients with N-AEs have anti-neural antibodies, and their presence associates with characteristic clinical syndromes and suggests a paraneoplastic origin.

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IMMUNE CHECKPOINT INHIBITOR-INDUCED MYOSITIS, THE EARLIEST AND MOST LETHAL COMPLICATION AMONG RHEUMATIC AND MUSCULOSKELETAL TOXICITIES

Session Type
PARALLEL SESSIONS
Date
29.05.2021, Saturday
Session Time
13:30 - 15:30
Room
HALL B
Lecture Time
14:50 - 15:00
Session Icon
Pre Recorded

Abstract

Background and Aims

In addition to restoring anti-tumor immune responses, immune checkpoint inhibitors (ICI) may also induce immune-related adverse events (irAE) that can affect any organ. We aim to determine the spectrum, timing, clinical features, and fatalities of rheumatic and musculoskeletal immune-related adverse events (RMS-irAE) associated with ICI.

Methods

We performed an observational, retrospective, pharmacovigilance study using the World Health Organization international pharmacovigilance database, VigiBase, from inception to January 2019. RMS-irAE reporting rate on ICI versus full database was performed using disproportionality analysis with computation of reporting-odds-ratios (ROR) and a Bayesian disproportional estimate (information component, IC). IC025 (lower end of the IC 95% credibility interval) >0 is deemed significant.

Results

We identified 1,288 RMS-irAE significantly associated with ICI: polymyalgia rheumatica (n=76, ROR=14.6 [11.6-18.4], IC025=3.34), sarcoidosis (n=94; ROR=9.6 [7.9-11.9]; IC025=2.85), Sjogren's syndrome (n=49; ROR=6.9 [5.2-9.2]; IC025=2.24), myositis (n=465; ROR=4.9 [4.5-5.4]; IC025=2.12), scleroderma (n=17; ROR=2.0 [1.2-3.2]; IC025=0.17), and arthritis (n=606; ROR=1.4 [1.3-1.5]; IC025=0.34). Arthritis, myositis, and Sjogren's syndrome were over-reported in patients treated with ICI combination versus those treated with ICI monotherapy (ROR=1.6-2.9, p<0.05) and more frequently reported on anti-PD1/PDL1 monotherapy vs. anti-CTLA4 monotherapy (2.1-4.4, p<0.05). Median time to onset occurred early for myositis (31 days [19.2-57.8]) and was the most delayed for scleroderma (395 days [323.8-457.2], p<0.0001). The fatality rate for RMS-irAE ranged from 24% for myositis (n=106/441) (up to 56.7% with concurrent myocarditis) to [0-6.7%] for other RMS-irAE (p<0.0001).

Conclusions

Clinicians should be aware of the spectrum of RMS-irAE. Myositis can be particularly life-threatening, particularly when associated with myocarditis.

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IMMUNE CHECKPOINT INHIBITOR THERAPY AND AUTOIMMUNE MANIFESTATIONS. A SINGLE BRAZILIAN CENTER EXPERIENCE.

Session Type
PARALLEL SESSIONS
Date
29.05.2021, Saturday
Session Time
13:30 - 15:30
Room
HALL B
Lecture Time
15:00 - 15:10
Session Icon
Pre Recorded

Abstract

Background and Aims

Immune Checkpoint Inhibitor Therapy and Autoimmune Manifestations. A single Brazilian center experience.Rafael A. Schmerling, Antonio c. Buzaid, Carolina k. Haddad, Fabio AB Schutz, Fabio r. Kater, Juliana Pimenta, Fernando Maluf, William N, Camila Lopes, Dafne Bromberg, Ana C. Oliveira, Morton Scheinberg. Oncology Center and Autoimmune Disease Nucleus Hospital Beneficiencia Portuguesa São Paulo Brazil 01323-030, Evaluate the prevalence and type of autoimmune events in patients receiving checkpoint inhibitor (ICIs).

Methods

A single center retrospective study was performed in cancer patients receiving ICIs on the period of 2012-2019.

Results

Five hundred and forty four patients received ICIs during this period.The mean age was 63.8 years 62% were male and the remainder female. The mean time of appearance was 5.5 months. Organ, autoimmune manifestation present were in the endocrine, skin, pulmonary,musculoskeletal, gastrointestinal and the nervous system, in a total of 123 patients.Twenty one had preexisting autoimmune disease and required treatment with steroids,hormone replacement and six also needed immunobiological.Toxicity classification was seen in grade 1(37.5%) grade 2 (43%) and grade 3 or 4(19.5%).Thirty three patients discontinued due to toxicity or lack of response.It was also possible to identify a positive correlation between tumor regression and the appearance of autoimmune signs and symptoms.Melanoma accounted for 34% of the patient population receiving ICIs during this period and autoimmunity was detected in 60% of the patients.

Conclusions

This is one of the largest single center experience in Latin America confirming the association of autoimmune diseases with ICIs therapy in cancer patients.Discontinuation of ICIs due to autoimmunity was a rare event.

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ANTICANCER IMMUNOTHERAPY AND RELATED ENDOCRINE ADVERSE EVENTS

Session Type
PARALLEL SESSIONS
Date
29.05.2021, Saturday
Session Time
13:30 - 15:30
Room
HALL B
Lecture Time
15:10 - 15:20
Presenter
Session Icon
Pre Recorded

Abstract

Background and Aims

New therapeutic approaches based on immune checkpoint inhibitor (ICI), that headed to unleash the immune system against cancer, have been recently investigated. Patients with melanoma, non-small-cell lung, bladder, renal, cervical, urotherial, and colorectal cancers, Merkel cell carcinoma, and Hodgkin lymphoma, showed notable improvements with ICI treatments. Monoclonal antibodies (mAbs) act on immune checkpoints, such as anti-CTLA-4 ( ipilimumab), anti-PD-1 (nivolumab, pembrolizumab), anti-PD-L1 (durvalumab, atezolizumab, avelumab), making the immune system able to react against tumor cells. ICIs are associated with immune-related adverse events (irAEs) that are clinically and pathophysiologically different from those caused by chemotherapies.

Methods

We have searched on Pubmed about ICI therapies and related endocrine adverse events.

Results

The most frequent endocrine irAEs related to anti-PD-1 mAb treatment are thyroid dysfunctions, whereas hypophysitis is mostly associated to anti-CTLA-4 treatment. Type 1 diabetes mellitus and adrenalitis are rare irAEs. The combination of anti-CTLA-4 plus anti-PD-1/PD-L1 therapies could be lead to an increased risk and prevalence of endocrine irAEs.

Conclusions

A tight collaboration among oncologists, endocrinologists and immunologists appears necessary when the circumstances are more challenging and for a better management of severe endocrine irAEs. More investigations are needed to better understand the mechanisms by which different ICIs can induce a variety of endocrine irAEs.

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