Pre-existing Autoimmune Disease Research Articles

Clinical features of patients with new onset of autoimmune hepatitis following SARS-CoV-2 vaccination

Introduction: Autoimmune hepatitis (AIH) is a relatively rare chronic immune-mediated liver disease, which develops in genetically predisposed individuals following an environmental trigger. A few cases of AIH have been recently reported after the SARS-CoV-2 vaccination. Aims: The aim of this study was to describe clinical-epidemiological profile of a series of adult patients who experienced AIH onset following SARS-CoV-2 vaccination. Materials and Methods: This multicentric observational study collected clinical data of adult patients who had received SARS-CoV-2 vaccination and thereafter were diagnosed with AIH between 03/2021 and 10/2021 in Italy, using an online survey among members of the Italian Association for the study of the Liver (AISF). Results: Among the 12 patients included: 50% were females, median age 62 years (range 32-80), 6 (50%) had preexisting extrahepatic autoimmune disease (3 thyroiditis, 2 rheumatoid arthritis, 1 systemic lupus erythematosus), 7 patients have received Comirnaty (BioNTech/Pfizer) vaccine, 2 Spikevax (Moderna Biotech) and 3 Vaxzevria (AstraZeneca). Ten patients (83%) had acute onset of AIH with transaminase levels ≥10 times the upper limit of normal (ULN, range 13-77 x ULN), 8 (67%) with jaundice (total bilirubin 3.5-18.6 x ULN). At AIH diagnosis (median time from first and second vaccine dose: 48 and 10 days, respectively) median AST was 18 x ULN (range 5-85), ALT 23.8 x ULN (range 7-83), total bilirubin 3.8 x ULN (range 0.6-18.6), alkaline phosphatase 1.3 x ULN (range 0.8-7.1), immunoglobulin G 1.2 x ULN (median 0.8-1.5). Eight (67%) patients had autoantibodies: 6 ANA, 1 SMA, 1 LKM-1. Liver biopsy was typical for AIH in 8 and compatible in 3 patients. After 3 months 58% achieved complete biochemical response to standard immunosuppressive treatment. Conclusion: While intensive vaccination against SARS-CoV-2 continues, the diagnosis of AIH secondary to vaccines should be included in the differential diagnosis in cases of acute hepatitis of unexplained aetiology.

SARS-CoV-2 vaccine in patients with thymic epithelial tumours with and without active or pre-existing autoimmune disorders: Brief report of a TYME network safety analysis

BackgroundInternational guidelines recommend severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine for patients with cancer.A substantial risk of developing vaccine-related autoimmune toxicities could be hypothesised for patients with thymic epithelial tumours (TETs) due to their high risk of autoimmune disorders (ADs). Moreover, a cross-reaction between SARS-CoV-2 spike protein antibodies and various tissue proteins has been shown, and antibodies against nucleoproteins showed overlaps in the autoimmune cross-reaction with antibodies to spike protein. Due to the rarity of TETs, no data addressing this hypothesis are available. MethodsPatients with TETs who received SARS-CoV-2 vaccine, treated in 4 referral centres of the Italian Collaborative Group for ThYmic MalignanciEs (TYME) network between February 2021 and September 2021, were interviewed through a standardised 15-items questionnaire in order to describe the safety of SARS-CoV-2 vaccine in patients affected by TETs. ResultsData from 245 doses of vaccine administered to 126 patients (41 = thymic carcinoma, 85 = thymoma; 38 with AD, of which 26 with active AD) were collected. Nine patients had a previous COVID-19-positive swab. No cases of AD reactivation or worsening of a pre-existing AD were seen in the study population. A new diagnosis of myasthenia gravis likely unrelated to the vaccine was made in two patients after the vaccination. Sixty-four patients (51%) experienced a total of 103 adverse events, all G1/G2, most commonly fatigue, new or worsening muscle pain and chills. None AE required patients’ hospitalisation. ConclusionsSARS-CoV-2 mRNA vaccines appear to be safe in patients with TET, even in case of active or pre-existing AD.

Pre-Existing Autoimmune Disease and Mortality in Patients Treated with Anti-PD-1 and Anti-PD-L1 Therapy.

Although indications for immune checkpoint inhibitors (ICIs) have dramatically increased in the past decade, ICIs have been associated with autoinflammatory immune-related adverse events, which can resemble autoimmune diseases (ADs). Little is known about the impact of baseline AD on mortality in cancer patients treated with ICIs. Here, we identified 17 497 patients with preexisting autoimmune diagnoses prior to treatment with antiprogrammed cell death receptor-1 or antiprogrammed cell death ligand-1 therapy and 17 497 matched controls through the TriNetX Diamond network of more than 200 million patients across the United States and Europe. Using a Cox proportional hazards model, we found that patients with history of AD were not at higher risk of mortality than non-AD patients (hazard ratio [HR] = 1.03, 95% confidence interval [CI] = 1 to 1.07; P = .05). Additionally, history of Hashimoto disease (HR = 0.75, 95% CI = 0.62 to 0.90; P = .002) and vitiligo (HR = 0.52, 95% CI = 0.34 to 0.81; P = .003) were statistically significantly associated with decreased mortality. This suggests that underlying AD need not be a contraindication to inclusion in clinical trials and administration of ICI for treatment of cancer.

Cancer and Autoimmune Diseases: A Tale of Two Immunological Opposites?

The present article compares, side-by-side, cancer and autoimmune diseases in terms of innate and adaptive immune cells involvement, MHC Class I and Class II expression, TGFβ effect, immune modulating drugs effect and the effect of reactive oxygen species. The change in the inflammatory immune reaction during the progress of cancer and the effect of this change on the comorbidity of autoimmune diseases and cancer are discussed. The similar inflammatory properties of autoimmune diseases and early cancer, and the contrasting inflammatory properties of autoimmune diseases and advanced cancer elucidate the increased incidence of many types of cancer in patients with pre-existing autoimmune diseases and the decreased cancer-specific mortality of these patients. Stage-dependent effects of reactive oxygen-species on tumor proliferation are an additional probable cause for these epidemiological observations. The relationship: {standardized incidence ratio (SIR)} > {cancer-specific hazard ratio (HR)} for cancer patients with a history of autoimmune diseases is substantiated and rationalized.

Predictors of Rheumatic Immune-Related Adverse Events and De Novo Inflammatory Arthritis After Immune Checkpoint Inhibitor Treatment for Cancer.

To identify predictors of rheumatic immune-related adverse events (irAEs) following immune checkpoint inhibitor (ICI) treatment for cancer. We performed a case-control study to predict the occurrence of rheumatic irAEs in cancer patients who initiated ICI treatment at Mass General Brigham and the Dana-Farber Cancer Institute between 2011 and 2020. We screened for the presence of rheumatic irAEs by reviewing the medical records of patients evaluated by rheumatologists or those prescribed nonglucocorticoid immunomodulatory drugs after the time of ICI initiation (baseline). Review of medical records confirmed the presence of rheumatic irAEs and the indications necessitating immunomodulatory drug treatment. Controls were defined as patients who did not experience rheumatic irAEs, did not have preexisting rheumatic disease, did not have a clinical evaluation by a rheumatologist after ICI treatment, did not receive an immunomodulatory drug after ICI, did not receive systemic glucocorticoids after ICI, and survived at least 6 months after the initial ICI treatment. We used logistic regression to estimate the odds ratios (ORs) (with 95% confidence intervals [95% CIs]) for the risk of a rheumatic irAE in the presence of various baseline predictors. A total of 8,028 ICI recipients were identified (mean age 65.5 years, 43.1% female, 31.8% with lung cancer). After ICI initiation, 404 patients (5.0%) were evaluated by rheumatologists, and 475 patients (5.9%) received an immunomodulatory drug to treat any irAEs. There were 226 confirmed rheumatic irAE cases (2.8%) and 118 de novo inflammatory arthritis cases (1.5%). Rheumatic diseases (either preexisting rheumatic diseases or rheumatic irAEs) were a common indication for immunomodulatory drug use (27.9%). Baseline predictors of rheumatic irAEs included melanoma (multivariable OR 4.06 [95% CI 2.54-6.51]) and genitourinary (GU) cancer (OR 2.22 [95% CI 1.39-3.54]), both relative to patients with lung cancer; combination ICI treatment (OR 2.35 [95% CI 1.48-3.74]), relative to patients receiving programmed death 1 inhibitor monotherapy; autoimmune disease (OR 2.04 [95% CI 1.45-2.85]) and recent glucocorticoid use (OR 2.13 [95% CI 1.51-2.98]), relative to patients not receiving a glucocorticoid, compared to the 2,312 controls without rheumatic irAEs. Predictors of de novo inflammatory arthritis were similar to those of rheumatic irAEs. We identified novel predictors of rheumatic irAE development in cancer patients, including baseline presence of melanoma, baseline presence of GU tract cancer, preexisting autoimmune disease, receiving or having received combination ICI treatment, and receiving or having received glucocorticoids. The proportion of cancer patients experiencing rheumatic irAEs may be even higher than was reported in the present study, since we used stringent criteria to identify cases of rheumatic irAEs. Our findings could be used to identify cancer patients at risk of developing rheumatic irAEs and de novo inflammatory arthritis and may help further elucidate the pathogenesis of rheumatic irAEs in patients with cancer who are receiving ICI treatment.

Biomarkers Associated with Immune-Related Adverse Events under Checkpoint Inhibitors in Metastatic Melanoma.

Simple SummaryOur aim was to check for possible associations between clinical parameters or NGS-based genetic alterations and the occurrence of immune-related adverse events (IRAE) in melanoma patients with immune checkpoint inhibitors (ICI). We analyzed 95 melanoma patients with ICI and were able to identify several biomarkers associated with the development of IRAE. Female sex was significantly associated with the development of hepatitis, increased total and relative monocytes at ICI initiation were significantly associated with the development of pancreatitis, the same, pre-existing autoimmune diseases. Furthermore, the following genetic alterations were identified being associated with IRAE: SMAD3 (pancreatitis); CD274, SLCO1B1 (hepatitis); PRDM1, CD274 (encephalitis); PRDM1, CD274, TSHR, FAN1 (myositis). Myositis and encephalitis, both, were associated with alterations of PRDM1 and CD274, which might explain their joined appearance in clinical practice. Our findings can help to assess the risk for the development of IRAE in melanoma patients with ICI.Immune checkpoint inhibitors (ICI) have revolutionized the therapeutic landscape of metastatic melanoma. However, ICI are often associated with immune-related adverse events (IRAE) such as colitis, hepatitis, pancreatitis, hypophysitis, pneumonitis, thyroiditis, exanthema, nephritis, myositis, encephalitis, or myocarditis. Biomarkers associated with the occurrence of IRAE would be desirable. In the literature, there is only little data available and furthermore mostly speculative, especially in view of genetic alterations. Our major aim was to check for possible associations between NGS-based genetic alterations and IRAE. We therefore analyzed 95 melanoma patients with ICI and evaluated their NGS results. We checked the data in view of potential associations between copy number variations (CNVs), small variations (VARs), human leucocyte antigen (HLA), sex, blood count parameters, pre-existing autoimmune diseases and the occurrence of IRAE. We conducted a literature research on genetic alterations hypothesized to be associated with the occurrence of IRAE. In total, we identified 39 genes that have been discussed as hypothetical biomarkers. We compared the list of these 39 genes with the tumor panel that our patients had received and focused our study on those 16 genes that were also included in the tumor panel used for NGS. Therefore, we focused our analyses on the following genes: AIRE, TERT, SH2B3, LRRK2, IKZF1, SMAD3, JAK2, PRDM1, CTLA4, TSHR, FAN1, SLCO1B1, PDCD1, IL1RN, CD274, UNG. We obtained relevant results: female sex was significantly associated with the development of hepatitis, combined immunotherapy with colitis, increased total and relative monocytes at therapy initiation were significantly associated with the development of pancreatitis, the same, pre-existing autoimmune diseases. Further significant associations were as follows: HLA homozygosity (hepatitis), and VARs on SMAD3 (pancreatitis). Regarding CNVs, significant markers included PRDM1 deletions and IL1RN (IRAE), CD274 duplications and SLCO1B1 (hepatitis), PRDM1 and CD274 (encephalitis), and PRDM1, CD274, TSHR, and FAN1 (myositis). Myositis and encephalitis, both, were associated with alterations of PRDM1 and CD274, which might explain their joined appearance in clinical practice. The association between HLA homozygosity and IRAE was clarified by finding HLA-A homozygosity as determining factor. We identified several genetic alterations hypothesized in the literature to be associated with the development of IRAE and found significant results concerning pre-existing autoimmune diseases and specific blood count parameters. Our findings can help to better understand the development of IRAE in melanoma patients. NGS might be a useful screening tool, however, our findings have yet to be confirmed in larger studies.

Systemic lupus erythematosus reactivation after chemoimmunotherapy in preexisting autoimmune disease.

The use of immune checkpoint inhibitors (ICIs) offers new possibilities in modern treatment of many types of cancers. Few data regarding safety and efficacy of ICIs are available, and are mainly from retrospective studies and case reports rather than from clinical trials, in the context of preexisting autoimmune disease, mainly due to the risk of severe toxicity. We present an unexpected life-threatening reactivation of systemic lupus erythematosus after one dose of chemo-immunotherapy with pembrolizumab for oligometastatic non-small-cell lung cancer. We analyze data coming from the published literature in this setting and discuss the risk-benefit balance of immunotherapy in patients with preexisting severe autoimmune disease.

Anti–programmed death ligand 1 immunotherapies in cancer patients with pre-existing systemic sclerosis: A postmarketed phase IV safety assessment study

ObjectivesCancer patients with pre-existing autoimmune disease, such as systemic sclerosis (SSc), are excluded from clinical trials, so the data on tolerability and efficacy of immune checkpoint inhibitors in these patients are limited. This study investigated the tolerability and efficacy of anti–programmed death ligand 1 (PD (L)1) immunotherapies in patients with pre-existing SSc. MethodsScleronco-01 was a multicentre, nationwide, open-label, phase IV observational study, from 2019 to 2021. ResultsSeventeen SSc patients receiving treatment for lung carcinoma (n = 13, 77%), head and neck cancer (n = 2, 12%), melanoma (n = 1, 6%), and colorectal carcinoma (n = 1, 6%) were included. The median (interquartile range) patient age was 60 (34–82) years. Fifteen (88%) patients received anti-PD1 (nivolumab and pembrolizumab) and two (12%) anti-PD-L1 (durvalumab). The median follow-up duration was 12 (range, 2–38) months. Four patients (24%) experienced flare-up of SSc symptoms. Ten patients (59%) developed an immune-related adverse event (grade I–II in 11 patients [65%], grade III–IV in one [6%]) without grade V. The overall response rate was 41% (7/17 patients). The median overall survival was 15.8 (95% confidence interval: 7.3 to not reached) months. ConclusionAnti-PD1 or PD-L1 immunotherapies are suitable options for cancer patients with pre-existing SSc. Longer follow-up periods are required for long-term safety analyses.

Treatment of Cutaneous Squamous Cell Carcinoma with Immune Checkpoint Inhibitors in Special Populations

Cutaneous squamous cell carcinoma (cSCC) may develop in patients with dysregulated immune activation (pre-existing autoimmune diseases or immunosuppression due to hematopoietic/solid organ transplant recipients), patients with a compromised immune function (long-term immunosuppression), and patients carrying chronic viral infections, or those affected by lymphoproliferative diseases. It should be also considered that patients presenting with immunosuppression have a high incidence of cSCC (65-250-times higher than general population), highlighting the central role played by the immune system in the development of cSCC. All these cases must be considered as "special populations" for treatment with immune checkpoint inhibitors (ICIs), as the safety and activity of these drugs have not been studied on these specific cases, since these patients were excluded from clinical trials leading to approval of ICIs. It is therefore important to gain as much information as possible from the analysis of real-life data, to derive an indication to be adopted in everyday clinical setting. Moreover, therapeutic alternatives other than ICIs are scarce, mainly consisting in chemotherapy and anti-EGFR agents, whose activity is lower than immunotherapy and whose toxicity (particularly with chemotherapy) are not sustainable by this frail population. Here, we describe the current evidence of treatment with ICIs in special populations and conclude that it is necessary to find a balance between treatment risks (toxicities) and benefits (efficacy), as well as engaging a multidisciplinary team of experts to thoroughly manage and treat these patients.

COVID-19 Vaccination in Adults with Immune Thrombocytopenia (ITP): Data from the Platelet Disorder Support Association (PDSA) Patient Registry

COVID-19 Vaccination in Adults with Immune Thrombocytopenia (ITP): Data from the Platelet Disorder Support Association (PDSA) Patient Registry

A Retrospective Multicenter Case Study Evaluating the Characteristics, Management and Outcome of Acquired Amegakaryocytic Thrombocytopenia

A Retrospective Multicenter Case Study Evaluating the Characteristics, Management and Outcome of Acquired Amegakaryocytic Thrombocytopenia

Daratumumab Plus Chemotherapy Induces Complete Responses in a Consecutive Series of Four Patients with Plasmablastic Lymphoma

Introduction:Plasmablastic lymphoma (PBL) is a rare and aggressive lymphoma most commonly seen in the setting of chronic immunosuppression, such as HIV infection and organ transplantation, or in patients with pre-existing lymphoproliferative or autoimmune disorders. PBL commonly presents at extranodal sites and carries a poor prognosis with a global overall survival of 9-15 months after initial diagnosis. Despite poor prognosis for patients with PBL, therapeutic strategies to target this disease are limited, as CHOP-like regimens have failed to produce durable remission, and no standard of care has been established. The cell of origin for PBL is believed to be the plasmablast, as PBL cells possess immunoblastic morphology and contain an immunohistochemical profile positive for plasmablast markers, such as CD38, CD138, and MUM1/IRF4, and negative for B cell markers, such as CD20, CD19, and PAX5. The similarities between PBL cells and multiple myeloma (MM) cells, a plasma cell neoplasm, have led to investigations of the efficacy of MM therapeutics for the treatment of PBL. Daratumumab is a first-in-class monoclonal antibody directed against CD38 that has shown efficacy in treating relapsed/refractory and newly diagnosed MM. Here, we describe the treatment of four patients with advanced-stage PBL in the context of varying degrees of immunosuppression using combination treatment with daratumumab and EPOCH.Methods:Four consecutive patients were treated with daratumumab plus chemotherapy. Three of the four patients were treated in the frontline setting and received low-dose EPOCH (vincristine, doxorubicin, etoposide daily for 4 days; cyclophosphamide day 5) with 16mg/kg daratumumab dosed on days 1 and 8 for 6 cycles. Patient #4 showed partial CD20 positivity, prompting Rituximab co-administration (R-EPOCH). Patient #3 was treated in the relapsed setting with 16mg/kg daratumumab in combination with lenalidomide, dexamethasone, and doxorubicin. She was treated for 12 months. Responses were followed by PET/CT imaging.Results:The four consecutive patients (2 female, 2 male) ranged in age from 26-88 and all had advanced-stage PBL (Table 1). Three of the four patients had some degree of immunosuppression (Patient #1- post-transplantation lymphoproliferative disorder (PTLD), Patient #2- HIV/AIDS, Patient #3- Chron's disease, Patient #4- no history of immunosuppression). All patients had a Ki67 proliferation index over 70% and demonstrated extranodal involvement of disease (bone n=3, intestine n=2, liver n=2; kidney n=1; adrenal n=1).The three patients that received daratumumab in combination with EPOCH demonstrated a complete response at their first disease assessment by PET/CT scan after cycle 2 (Patient #1) or cycle 4 (Patients #2,4) (Fig1). Patient #3, who demonstrated a mixed response to previous therapy, achieved a complete response 5 months after starting treatment with daratumumab in combination with chemotherapy. As of July 2021, three of the four patients continued to have no evidence of disease for a median of 17 months (range 15-19 months). Patient #4 relapsed in July 2021, 3 months after demonstrating a complete response. Adverse events that required hospitalization were rarely noted following daratumumab treatment but included neutropenic fever (n=2, one event following treatment cycle 4 and the other event 2 months after completion of daratumumab administration), COVID-19 infection (n=1), and a PICC line-associated thrombus (n=1). Minor events were also noted and included self-limiting bradycardia (n=1), neuropathy (n=1), and rigor (n=1).Conclusions:We describe four patients with varying degrees of immunosuppression and HIV-status with aggressive-stage PBL that achieved complete response following treatment with daratumumab in combination with low-dose EPOCH or other chemotherapy. Three of four patients obtained durable responses. At the time of this writing, three additional HIV +patients have initiated treatment with daratumumab but have not yet reached their first disease assessment. Disease progression for these patients will be monitored and presented as part of this study. Our findings suggest a potential efficacy and warrant further investigation of using daratumumab for the treatment of HIV +and HIV - PBLs. [Display omitted] DisclosuresAmengual: Epizyme, Inc.: Speakers Bureau; Appia Pharmaceuticals: Research Funding; Daiichi Sankyo, Inc: Consultancy; Seagen: Consultancy. OffLabel Disclosure:our work uses daratumumab, a first-in-class monoclonal antibody against CD38 for the treatment of plasmablastic lymphoma

Interleukin-6 blockade for prophylaxis and management of immune-related adverse events in cancer immunotherapy

BackgroundImmune checkpoint inhibitors (ICIs) have activity across many tumor types, but activation of the immune system may also lead to significant, often steroid-refractory immune-related adverse events (irAEs). We sought to determine the activity of tocilizumab, an anti-interleukin-6 receptor monoclonal antibody, in treatment or prevention of auto-immune irAE in ICI-treated patients. MethodsInstitutional databases from 2 melanoma centers were reviewed for patients treated with ICIs and tocilizumab. Longitudinal assessment of C-reactive protein (CRP) and assessment of clinical improvement or prevention of flare of pre-existing auto-immune conditions were utilised to evaluate the benefit of tocilizumab. ResultsTwenty-two patients were identified. Two were treated prophylactically. Twenty were treated for management of irAEs. Median time to irAE onset from ICI start was 48 days (range 8–786) and from irAE onset to tocilizumab 32 days (range 1–192). Median time to irAE resolution from tocilizumab was 6.5 days (range 1–93). Clinical improvement/benefit was demonstrated in 21/22 patients. Median CRP prior to ICI administration was 32 mg/l (range 0.3–99), at the onset of irAE 49.5 mg/L (range 0.3–251, P = 0.047) and after tocilizumab 18 mg/L (range 0.3–18, P = 0.0011). Tocilizumab was well tolerated with self-limiting and transient toxicities in 11 (50%) patients. From start of ICI, median progression-free survival was 6 months (range 3.9–18.8) and median overall survival was not reached. ConclusionsTocilizumab was a well-tolerated and effective steroid-sparing treatment for both management of irAEs, as well as prevention of flare of pre-existing auto-immune disorders. Prospective trials to evaluate its efficacy and impact on cancer outcomes compared with standard strategies are required.

Tolerability of Coronavirus Disease 2019 Vaccines, BNT162b2 and mRNA-1273, in Patients With Thymic Epithelial Tumors

IntroductionDefects in immunologic self-tolerance result in an increased risk for development of paraneoplastic autoimmune diseases (ADs) and immune-mediated toxicity in response to immune stimulation in individuals with thymic epithelial tumors (TETs). We conducted a survey to evaluate the tolerability of coronavirus disease 2019 (COVID-19) mRNA vaccines in patients with TETs, including individuals with preexisting AD. MethodsAfter reviewing published data on adverse events associated with the BNT162b2 (Pfizer, Inc., and BioNTech) and mRNA-1273 (ModernaTX, Inc.) mRNA vaccines, we designed and administered a questionnaire to participants at the following three time points: after each dose of vaccination and 1 month after the final dose. Questions related to AD and use of immunosuppressive drugs were included. Descriptive statistics were used to analyze data, and results were compared with previously described results related to the BNT162b2 and mRNA-1273 vaccines. ResultsFrom February 26 to June 1, 2021, we administered the survey to 54 participants (median age = 58 y, thymoma = 33, preexisting AD = 19). Common adverse events included injection site pain, fatigue, and headaches. There were no vaccination-related hospitalizations or deaths. Autoimmune flares occurred in three patients (16%) after the first dose and three patients (17%) after the second dose. Most AD flares were mild and self-limited. One patient (2%) was diagnosed with having a new AD after vaccination. ConclusionsTolerability of COVID-19 mRNA vaccines in patients with TETs is comparable to the general population. Most patients with preexisting AD did not experience disease flares, and the development of new AD was rare. Patients with TETs should be encouraged to get vaccinated against COVID-19 owing to the documented benefits of vaccination and manageable risk profile.

Maladies auto-immunes, cancers bronchiques et immunothérapies: Autoimmune diseases, lung cancers and immunotherapies

Immune checkpoint inhibitors are today an essential therapy for the management of primary lung cancer. These monoclonal antibodies nevertheless expose patients to immune-related adverse events. Do patients with preexisting autoimmune disease derive the same benefit from immunotherapy as others? Are they more at risk of toxicity? What is the risk of flare of their underlying autoimmune disease? The aim of this article is to synthesize the data available in the literature on the use of immune checkpoint inhibitors in patients with both lung cancer and autoimmune disease.© 2021 SPLF. Published by Elsevier Masson SAS. All rights reserved.

B-PO04-174 USE OF PET-CT IMAGING TO GUIDE TREATMENT OF VENTRICULAR TACHYCARDIA

Cardiac inflammation plays a significant role in the development of ventricular tachycardia (VT); however, the optimal treatment strategies remain unknown. PET-CT imaging can reveal underlying inflammation and select patients who may benefit from immunosuppression. Determine the utility of PET-CT in guiding management decisions for ventricular tachycardia. We retrospectively reviewed all patients who underwent PET-CT for VT at UCLA between 2012-2019. Clinical characteristics including PET-CT results, treatment, and outcomes were collected. Patients with pre-existing autoimmune disease or taking immunosuppressive medication prior to evaluation were excluded. PET-CT was performed in 137 patients (median age 58 years, 79.6% male, mean LVEF 45%) for VT. A cardiac inflammatory process was found in 33 scans, while 104 were negative or inconclusive. Patients were followed for a median of 27.6 months (IQR: 3.3, 54.9). Of the patients with positive PET scans, 21 were initially treated with immunosuppression (3 developed recurrent VT requiring a subsequent ablation), 6 were treated with concurrent ablation and immunosuppression, 1 was treated with ablation alone (patient ended up receiving a heart transplant), and 5 were managed with antiarrhythmic medications. There was no significant difference in recurrence between PET-positive and PET-negative groups (39.3% vs 32.4%; p = 0.50) or time to recurrence (p = 0.89). Of the PET-positive patients receiving immunosuppression, 8/21 (38.1%) had recurrence. Of the PET-negative patients who underwent ablation, 22/54 (40.7%) had recurrence. There was no significant difference in outcomes comparing PET-positive immunosuppression only versus PET-negative ablation patients (p=0.83). PET-CT can identify patients with a cardiac inflammatory process who may benefit from immunosuppression. In patients with PET-positive imaging, treatment with immunosuppression yielded similar results as in patients without inflammation who underwent ablation in this series. The incorporation of PET-CT imaging into the evaluation for ventricular arrhythmias can potentially obviate the need for invasive procedures.

Challenges of Immunotherapy in Stage IV Non-Small-Cell Lung Cancer.

Treatment for metastatic non-small-cell lung carcinoma has seen important advances in recent years with the introduction of targeted therapies and immunotherapy. Immune checkpoint inhibitors, which target the programmed death 1 receptor and programmed death ligand-1, alone or in combination with platinum-based chemotherapy, have become standard of care in the first-line setting for patients with advanced non-small-cell lung carcinoma without targetable driver mutations. However, several clinical questions have now since emerged. Physicians treating lung cancer lack guidance when treating patients who have a poor performance status, patients who are receiving corticosteroids, and those known for pre-existing autoimmune disorders. Furthermore, data are scarce on rechallenging a patient with immune checkpoint inhibitors after the occurrence of a significant immune-related adverse event. In this review, we aim to shed light on these topics.

Reactivation of IgA vasculitis after COVID-19 vaccination.

Uncertainty persists as to the possibility that the COVID-19 vaccines might cause exacerbation of pre-existing autoimmune diseases.1 Here we report a case of reactivation of IgA vasculitis occurring after COVID-19 vaccination.

Use of immune checkpoint inhibitors in patients with solid tumors and pre-existing autoimmune or inflammatory disease: real-world data.

Aim:Immune checkpoint inhibitors (ICIs) are a cornerstone in cancer treatment but they can induce immune-related adverse events (irAEs). Furthermore, patients with pre-existing autoimmune and/or inflammatory disease (AID) have been excluded from clinical trials. The objective of this study is to evaluate the efficacy and safety of ICIs in patients with cancer and AID.Materials & methods:This is an observational, retrospective study carried out at the Medical Oncology Department of Hospital Universitario Puerta de Hierro, Majadahonda, Madrid between January 2016 and December 2018.Results:A total of 202 cancer patients treated with ICIs were included, 15 (7, 4%) of them had pre-existing autoimmune diseases. The most frequent pre-existing AID were thyroid diseases (33.3%): autoimmune hypothyroidism, Graves–Basedow disease and Hashimoto’s thyroiditis. Three patients had psoriasis, two antinuclear antiboides + polyarthritis, one rheumatoid arthritis, another latent autoimmune diabetes in adults, another systemic lupus erythematosus and the last one, a polymyalgia rheumatica. In this series, the majority of patients (73.33%) did not experience any flare up of their autoimmune disease. In patients who had AID flare up, this was treated with corticosteroids. The most frequent cause of immunotherapy discontinuation was tumor progression (40%). A total of 20% of patients had to discontinue immunotherapy due to toxicity.Conclusion:In our series, AID flare ups or irAEs in patients with pre-existing AID who receive immunotherapy are not very common and can often be controlled without interrupting treatment. Prospective studies are needed to establish the incidence of irAEs in patients with pre-existing autoimmune conditions, evaluate risk–benefit and elaborate management clinical guidelines in this population.

Preexisting autoimmune disease is a risk factor for immune-related adverse events: a meta-analysis.

Patients with preexisting autoimmune disease (PAD) are often excluded from clinical trials assessing immune checkpoint inhibitors (ICIs). Therefore, the safety of ICI therapy in patients with PAD remains unclear. Herein, we evaluated the incidence of immune-related adverse events (irAEs) in patients with PAD when compared with non-PAD patients. We searched MEDLINE/PubMed, Web of Science, and Google Scholar for eligible studies from inception to January 2021. Observational studies reporting the incidence of irAEs in patients with and without PAD were included. We then performed a meta-analysis of eligible studies using forest plots. The primary endpoint of this study was the incidence rate of irAEs between patients with and without PAD. We identified three prospective and three retrospective studies involving 206 patients with PAD and 3078 patients without PAD. In the meta-analysis, 128 patients with PAD (62.1%) experienced irAEs, which occurred in 51.9% of non-PAD patients, resulting in an odds ratio (OR) of 2.14 (95% confidence interval [CI] 1.58-2.89). In the subgroup analysis, the incidence of irAEs was significantly higher in patients with PAD (OR = 2.19, 95% CI [1.55-3.08]). Furthermore, no significant heterogeneity or publication bias was detected, indicating that our meta-analysis could be generalized to clinical settings. This meta-analysis demonstrated that PAD was a risk factor for irAE incidence. These results suggest that monitoring the occurrence of irAEs in patients with PAD is required to manage irAEs appropriately.