Autoimmunity Against Surfactant Protein B Is Associated with Pneumonitis During Checkpoint Blockade.

Immune checkpoint inhibitor (ICI)-related pneumonitis is a serious autoimmune event affecting as many as 20% of patients with non-small-cell lung cancer (NSCLC), yet the factors underpinning its development in some patients and not others are poorly understood. To investigate the role of autoantibodies and autoreactive T cells against surfactant-related proteins in the development of pneumonitis. The study cohort consisted of patients with NSCLC who provided blood samples before and during ICI treatment.

Immune signatures predict development of autoimmune toxicity in patients with cancer treated with immune checkpoint inhibitors.

Background: Immune checkpoint inhibitors (ICIs) are among the most promising treatment options for melanoma and non-small cell lung cancer (NSCLC). While ICIs can induce effective anti-tumor responses, they may also drive serious immune-related adverse events (irAEs). Identifying biomarkers to predict which patients will suffer from irAEs would enable more accurate clinical risk-benefit analysis for ICI treatment and may also shed light on common or distinct mechanisms underpinning treatment success and irAEs.

Mycophenolate mofetil as second line treatment in autoimmune hepatitis - A retrospective single center analysis.

Background: Most patients with autoimmune hepatitis respond to standard treatment with steroids and azathioprine. While the disease is usually fatal if untreated, patients who respond well to therapy have an excellent prognosis. Nevertheless, second-line treatment is necessary in approximately 20% of patients, due to either intolerance or insufficient response to first line treatment.

Autoreactive napsin A-specific T cells are enriched in lung tumors and inflammatory lung lesions during immune checkpoint blockade.

Cancer treatment with immune checkpoint blockade (ICB) often induces immune-related adverse events (irAEs). We hypothesized that proteins coexpressed in tumors and normal cells could be antigenic targets in irAEs and herein described DITAS (discovery of tumor-associated self-antigens) for their identification. DITAS computed transcriptional similarity between lung tumors and healthy lung tissue based on single-sample gene set enrichment analysis.

C reactive protein flare predicts response to checkpoint inhibitor treatment in non-small cell lung cancer.

Biomarkers for predicting response to anti-programmed death-1 (PD-1) immune checkpoint blockade (ICB) in non-small cell lung cancer (NSCLC) remain in demand. Since anti-tumor immune activation is a process, early dynamic changes of the acute-phase reactant C reactive protein (CRP) may serve as a predictive on-treatment biomarker. In a retrospective (N=105) and prospective (N=108) ICB-treated NSCLC cohort, early CRP kinetics were stratified after the start of immunotherapy until weeks 4, 6, and 12 as follows: an early doubling of baseline CRP followed by a drop below baseline (CRP flare-responder), a drop of at least 30% below baseline without prior flare (CRP responders), or those who remained as CRP non-responders.

Presence of autoantibodies in serum does not impact the occurrence of immune checkpoint inhibitor-induced hepatitis in a prospective cohort of cancer patients.

Purpose: Immune checkpoint inhibitor (ICI)-induced hepatitis belongs to the frequently occurring immune-related adverse events (irAEs), particularly with the combination therapy involving ipilimumab and nivolumab. However, predisposing factors predicting the occurrence of ICI-induced hepatitis are barely known. We investigated the association of preexisting autoantibodies in the development of ICI-induced hepatitis in a prospective cohort of cancer patients.

Accelerated Course of Alveolar Echinococcosis After Treatment With Steroids in a Patient With Autoimmune Encephalitis.

Human alveolar echinococcosis (AE) is a zoonotic infection caused by the fox tapeworm ​​​​​​ We report the case of a patient who developed an accelerated course of AE with diffuse liver involvement after high-dose steroid treatment for autoimmune encephalitis. Immunosuppressive therapies present us with new challenges regarding the management of AE. With this article, we would like to draw attention to the importance of a screening program for AE before planned immunosuppressive therapy.

Pretreatment metastatic growth rate determines clinical outcome of advanced melanoma patients treated with anti-PD-1 antibodies: a multicenter cohort study.

Background: Checkpoint inhibitors revolutionized the treatment of metastatic melanoma patients. Although tumor burden and lactate dehydrogenase (LDH) are associated with overall survival (OS), the impact of tumor growth kinetics remains elusive and in part contradictory. The aims of this study were to develop a novel simple and rapid method that estimates pretreatment metastatic growth rate (MGR) and to investigate its prognostic impact in melanoma patients treated with antiprogrammed death receptor-1 (PD-1) antibodies.

First-line treatment of NRAS-mutated metastatic melanoma with a MEK inhibitor.

Until recently, standard treatment for advanced melanoma comprised basically dacarbazine and interleukin-2, leading to low response rates and significant toxicity. These days, new treatments such as immunotherapy (anti-CTLA4 and anti-PD1 antibodies) and targeted therapy with BRAF/MEK-inhibitor combinations for patients harboring a BRAF mutation are available. In BRAF wild-type patients harboring an NRAS mutation, not fit for immunotherapy treatment options are still dismal.

Association of Supporting Trial Evidence and Reimbursement for Off-Label Use of Cancer Drugs.

Importance: In many health systems, access to off-label drug use is controlled through reimbursement restrictions by health insurers, especially for expensive cancer drugs.

Objective: To determine whether evidence from randomized clinical trials is associated with reimbursement decisions for requested off-label use of anticancer drugs in the Swiss health system.

Design, Setting, And Participants: This cross-sectional study used reimbursement requests from routinely collected health records of 5809 patients with drug treatment for cancer between January 2015 and July 2018 in 3 major cancer centers, covering cancer care of approximately 5% of the Swiss population, to identify off-label drug use.

Fingolimod and tumor-infiltrating lymphocytes in checkpoint-inhibitor treated cancer patients.

Immune checkpoint inhibitors (ICIs) are emerging as the new standard of care for treating various metastatic cancers. It is known that effective anti-tumor immune responses are associated with a stronger presence of tumor-infiltrating lymphocytes (TILs) in solid tumor tissue. Cancer patients with relapsing-remitting multiple sclerosis (RRMS) are often under continuous treatment with fingolimod, an immune-modulating drug that inhibits lymphocyte egress from secondary lymphatic organs.

Five-year review of corticosteroid duration and complications in the management of immune checkpoint inhibitor-related diarrhoea and colitis in advanced melanoma.

Background: Immune-related diarrhoea/colitis (ir-D/C) is a common adverse event of immune checkpoint inhibitor (ICI) therapy. Guidelines recommend corticosteroid (CS) treatment; however, the average treatment duration for ir-D/C remains poorly defined.

Methods: All advanced melanoma patients treated with ICI therapy at the Royal Marsden Hospital between 2011 and 2016 were reviewed to identify ir-D/C cases alongside clinical variables.

Contrasting evidence to reimbursement reality for off-label use (OLU) of drug treatments in cancer care: rationale and design of the CEIT-OLU project.

Background: Off-label use (OLU) of a drug reflects a perceived unmet medical need, which is common in oncology. Cancer drugs are often highly expensive and their reimbursement is a challenge for many healthcare systems. OLU is frequently regulated by reimbursement restrictions.

BP180-specific IgG is associated with skin adverse events, therapy response, and overall survival in non-small cell lung cancer patients treated with checkpoint inhibitors.

Background: Anti-programmed cell death protein 1 (PD1)/programmed death-ligand 1(PD-L1) therapy frequently entails immune-related adverse events (irAEs), and biomarkers to predict irAEs are lacking. Although checkpoint inhibitors have been found to reinvigorate T cells, the relevance of autoantibodies remains elusive.

Objective: Our aim was to explore whether IgG autoantibodies directed against coexpressed antigens by tumor tissue and healthy skin correlate with skin irAEs and therapy outcome.

Association of Checkpoint Inhibitor-Induced Toxic Effects With Shared Cancer and Tissue Antigens in Non-Small Cell Lung Cancer.

Importance: Immunotherapy with checkpoint inhibitors targeting the PD-1 (programmed cell death 1) axis has brought notable progress in patients with non-small cell lung cancer (NSCLC) and other cancers. However, autoimmune toxic effects are frequent and poorly understood, making it important to understand the pathophysiologic processes of autoimmune adverse effects induced by checkpoint inhibitor therapy.

Objective: To gain mechanistic insight into autoimmune skin toxic effects induced by anti-PD-1 treatment in patients with non-small cell lung cancer.

Antibodies as biomarker candidates for response and survival to checkpoint inhibitors in melanoma patients.

Background: Long-term survival of stage IV melanoma patients has improved significantly with the development of immune checkpoint inhibitors (CIs). Reliable biomarkers to predict response and clinical outcome are needed.

Methods: We investigated the role of melanoma-associated antibodies as predictive markers for CI therapy in two independent cohorts.

Risk score for non-small cell lung cancer patients starting checkpoint inhibitor treatment.

Background: Prognosis of metastatic non-small cell lung cancer significantly improved with the availability of checkpoint inhibitors (anti-PD-1/PD-L1). Unfortunately, reliable biomarkers to predict treatment benefit are lacking.

Patients And Methods: We prospectively collected clinical and laboratory data of 56 non-small cell lung cancer patients treated with a checkpoint inhibitor.

Organ-specific response to nivolumab in patients with non-small cell lung cancer (NSCLC).

Background: Response to immune checkpoint inhibitors depends on tumor intrinsic properties and also on host factors in the tumour microenvironment including the presence of immune cells (IC). We hypothesized that nivolumab efficacy varies across different metastatic sites.

Methods: We retrospectively analyzed computed tomography scans of patients with metastatic non-small cell lung carcinoma (NSCLC) receiving nivolumab.

Cohort Profile: The Swiss Eosinophilic Esophagitis Cohort Study (SEECS).

Background And Aims: The prospective, observational Swiss Eosinophilic Esophagitis Cohort Study (SEECS) was set up in 2015 with the following goals in mind: (1) to provide up-to-date epidemiologic data; (2) to assess the appropriateness of care; (3) to evaluate the psychosocial impact; and (4) to foster translational research projects. Data capture relies on validated instruments to assess disease activity and focuses on epidemiologic variables and biosamples (esophageal biopsies and blood specimens). An annual inclusion of 70 new patients with eosinophilic esophagitis (EoE) or proton pump inhibitor-responsive esophageal eosinophilia (PPI-REE) is intended.

Tumor infiltrating lymphocytes in lymph node metastases of stage III melanoma correspond to response and survival in nine patients treated with ipilimumab at the time of stage IV disease.

Prognosis of metastatic melanoma improved with the development of checkpoint inhibitors. The role of tumor infiltrating lymphocytes (TILs) in lymph node metastases of stage III melanoma remains unclear. We retrospectively characterized TILs in primary melanomas and matched lymph node metastases (stage III melanoma) of patients treated with the checkpoint inhibitor ipilimumab.

Neutrophil-to-Lymphocyte ratio (NLR) and Platelet-to-Lymphocyte ratio (PLR) as prognostic markers in patients with non-small cell lung cancer (NSCLC) treated with nivolumab.

Objectives: Immunotherapy with the programmed death receptor-1 (PD-1) antibody nivolumab has changed the field of metastatic non-small cell lung cancer (NSCLC) treatment. Nivolumab shows better outcome compared to standard second line chemotherapy, but reliable prognostic markers are lacking. High neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are markers of host inflammation and associated with worse overall survival (OS) in several tumor types, but have not been analysed extensively in lung cancer in the era of immunotherapy.

Outcome of patients older than 80 years with diffuse large B-cell lymphoma (DLBCL) treated with "standard" immunochemotherapy: A large retrospective study from 4 institutions.

Little information is available on the very elderly patients with diffuse large B-cell lymphoma (DLBCL). We performed a retrospective analysis of 281 patients >80 years old with newly diagnosed DLBCL treated in 4 referral institutions in Switzerland and Northern Italy. Primary end points were overall survival, progression-free survival, and cause-specific survival.