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Nonmelanoma skin cancers (NMSCs) are some of the most commonly diagnosed malignancies. In general, early-stage NMSCs have favorable outcomes; however, a small subset of patients develop resistant, advanced, or metastatic disease, or aggressive subtypes that are more challenging to treat successfully. Recently, immune checkpoint inhibitors (ICIs) have been approved by the US Food and Drug Administration (FDA) for the treatment of Merkel cell carcinoma (MCC), cutaneous squamous cell carcinoma (CSCC), and basal cell carcinoma (BCC). Although ICIs have demonstrated activity against NMSCs, the routine clinical use of these agents may be more challenging due to a number of factors including the lack of predictive biomarkers, the need to consider special patient populations, the management of toxicity, and the assessment of atypical responses. With the goal of improving patient care by providing expert guidance to the oncology community, the Society for Immunotherapy of Cancer (SITC) convened a multidisciplinary panel of experts to develop a clinical practice guideline (CPG). The expert panel drew on the published literature as well as their own clinical experience to develop recommendations for healthcare professionals on important aspects of immunotherapeutic treatment for NMSCs, including staging, biomarker testing, patient selection, therapy selection, post-treatment response evaluation and surveillance, and patient quality of life (QOL) considerations, among others. The evidence- and consensus-based recommendations in this CPG are intended to provide guidance to cancer care professionals treating patients with NMSCs.

Basal cell carcinoma (BCC) is the most common malignancy worldwide, yet the management of patients with advanced or metastatic disease is challenging, with limited treatment options. Recently, programmed death receptor 1 (PD-1) inhibition has demonstrated activity in BCC after prior Hedgehog inhibitor treatment. We conducted a multicenter, retrospective analysis of BCC patients treated with PD-1 inhibitor therapy. We examined the efficacy and safety of PD-1 therapy, as well as clinical and pathological variables in association with outcomes. Progression-free survival (PFS), overall survival (OS) and duration of response (DOR) were calculated using Kaplan-Meier methodology. Toxicity was graded per Common Terminology Criteria for Adverse Events V.5.0. A total of 29 patients with BCC who were treated with PD-1 inhibition were included for analysis, including 20 (69.0%) with locally advanced and 9 (31.0%) with metastatic disease. The objective response rate was 31.0%, with five partial responses (17.2%), and four complete responses (13.8%). Nine patients had stable disease (31.0%), with a disease control rate of 62.1%. The median DOR was not reached. Median PFS was 12.2 months (95% CI 0.0 to 27.4). Median OS was 32.4 months (95% CI 18.1 to 46.7). Two patients (6.9%) developed grade 3 or higher toxicity, while four patients (13.8%) discontinued PD-1 inhibition because of toxicity. Higher platelets (p=0.022) and any grade toxicity (p=0.024) were significantly associated with disease control rate. The clinical efficacy of PD-1 inhibition among patients with advanced or metastatic BCC in this real-world cohort were comparable to published trial data. Further investigation of PD-1 inhibition is needed to define its optimal role for patients with this disease.

BackgroundAtopic diseases, which are characterized by IgE-mediated sensitization involving mast cells, basophils, and adaptive immune cells have an unclear role in cancer development and immune-related adverse events (irAEs). Atopy may heighten immune system surveillance and tumor elimination. Conversely, chronic immune activation may also promote oncogenesis via pro-inflammatory signaling and lead to T-cell exhaustion. We hypothesized that patients with atopy would have increased clinical benefit and increased toxicity to immune checkpoint inhibitors (ICI).MethodsWe conducted a retrospective analysis of patients in the Scripps Health System between 2017 and 2024. Eligible patients had a diagnosis of cancer (including melanoma, squamous cell carcinoma, basal cell carcinoma, Merkel cell carcinoma, lung adenocarcinoma, Hodgkin lymphoma, renal cell carcinoma, cholangiocarcinoma, cervical cancer, hepatocellular carcinoma, or bladder cancer), received an ICI, and carried a concurrent diagnosis of an atopic condition (atopic dermatitis, food allergy, or asthma) with allergist evaluation documented in the system.ResultsInterim data analysis included 289 patients with stage I (n=1), stage II (n=17), stage III (n=96), and stage IV (n=175) disease at initiation of ICI. 46 patients were on antihistamines or montelukast and 5 received dupilumab. PD-L1 expression was available for 17 patients with a median expression of 25%. Median follow-up from biopsy and ICI initiation was 2.2 and 1.6 years, respectively. Median ICI duration was 6 months. Best response on therapy included complete response (CR, n=107), partial response (n=61), stable disease (n=56), and disease progression (n=49) patients. Reasons for immunotherapy discontinuation include CR (n=74), disease progression (n=82), and toxicity (n=52). A total of 155 irAEs occurred among 132 patients (46%) including 43 (27.7%) events classified as grade 3 or 4. Most common irAEs include thyroid dysfunction (n=34, 12%), dermatitis (n=29, 10%), colitis (n=26, 9%), pneumonitis (n=25, 9%), and hepatitis (n=14, 5%). Corticosteroids were prescribed in 91 cases and tapered over a median of 8 weeks. Fifteen patients received a biologic (most commonly infliximab).ConclusionsPublished irAE incidence ranges from 80-85%% overall and 3–40% for grade ≥3 events depending on ICI class and whether combination regimens are used.1 2 Our atopic cohort exhibited a higher rate of irAEs and severe toxicities, despite deriving similar therapeutic benefit. These findings underscore the need for further investigation into the immunobiology and optimal management of irAEs in patients with atopic disease.ReferencesJayathilaka B, Mian F, Franchini F, Au-Yeung G, IJzerman M. Cancer and treatment specific incidence rates of immune-related adverse events induced by immune checkpoint inhibitors: a systematic review. Br J cancer 2025;132(1):51–7.Fujii T, Colen RR, Asim Bilen M, Hess KR, Hajjar J, Suarez-Almazor ME, et al. Incidence of immune-related adverse events and its association with treatment outcomes: the MD Anderson Cancer Center experience. Invest New Drugs 2017;36(4):638–46.

Advances in the treatment of metastatic melanoma have improved responses and survival. However, many patients continue to experience resistance or toxicity to treatment, highlighting a crucial need to identify biomarkers and understand mechanisms of response and toxicity. Neoadjuvant therapy for regional metastases might improve operability and clinical outcomes over upfront surgery and adjuvant therapy, and has become an established role for drug development and biomarker discovery in other cancers (including locally advanced breast cancer, head and neck squamous cell carcinomas, gastroesophageal cancer, and anal cancer). Patients with clinically detectable stage III melanoma are ideal candidates for neoadjuvant therapy, because they represent a high-risk patient population with poor outcomes when treated with upfront surgery alone. Neoadjuvant therapy is now an active area of research for melanoma with numerous completed and ongoing trials (since 2014) with disparate designs, endpoints, and analyses under investigation. We have, therefore, established the International Neoadjuvant Melanoma Consortium with experts in medical oncology, surgical oncology, pathology, radiation oncology, radiology, and translational research to develop recommendations for investigating neoadjuvant therapy in melanoma to align future trial designs and correlative analyses. Alignment and consistency of neoadjuvant trials will facilitate optimal data organisation for future regulatory review and strengthen translational research across the melanoma disease continuum.

BackgroundTo date, no systemic therapy, including immunotherapy, exists to improve clinical outcomes in metastatic uveal melanoma (UM) patients. To understand the role of immune infiltrates in the genesis, metastasis, and response to treatment for UM, we systematically characterized immune profiles of UM primary and metastatic tumors, as well as samples from UM patients treated with immunotherapies.MethodsRelevant immune markers (CD3, CD8, FoxP3, CD68, PD-1, and PD-L1) were analyzed by immunohistochemistry on 27 primary and 31 metastatic tumors from 47 patients with UM. Immune gene expression profiling was conducted by NanoString analysis on pre-treatment and post-treatment tumors from patients (n=6) receiving immune checkpoint blockade or 4-1BB and OX40 dual costimulation. The immune signature of UM tumors responding to immunotherapy was further characterized by Ingenuity Pathways Analysis and validated in The Cancer Genome Atlas data set.ResultsBoth primary and metastatic UM tumors showed detectable infiltrating lymphocytes. Compared with primary tumors, treatment-naïve metastatic UM showed significantly higher levels of CD3+, CD8+, FoxP3+ T cells, and CD68+ macrophages. Notably, levels of PD-1+ infiltrates and PD-L1+ tumor cells were low to absent in primary and metastatic UM tumors. No metastatic organ-specific differences were seen in immune infiltrates. Our NanoString analysis revealed significant differences in a set of immune markers between responders and non-responders. A group of genes relevant to the interferon-γ signature was differentially up-expressed in the pre-treatment tumors of responders. Among these genes, suppressor of cytokine signaling 1 was identified as a marker potentially contributing to the response to immunotherapy. A panel of genes that encoded pro-inflammatory cytokines and molecules were expressed significantly higher in pre-treatment tumors of non-responders compared with responders.ConclusionOur study provides critical insight into immune profiles of UM primary and metastatic tumors, which suggests a baseline tumor immune signature predictive of response and resistance to immunotherapy in UM.

Purpose Sclerosing mesenteritis (SM), a fibroinflammatory process of the mesentery, can rarely occur after immune checkpoint inhibitor (ICI) therapy; however, its clinical significance and optimal management are unclear. We aimed to assess the characteristics and disease course of patients who developed SM following ICI therapy at a single tertiary cancer center. Methods We retrospectively identified 12 eligible adult cancer patients between 05/2011 and 05/2022. Patients’ clinical data were evaluated and summarized. Results The median patient age was 71.5 years. The most common cancer types were gastrointestinal, hematologic, and skin. Eight patients (67%) received anti-PD-1/L1 monotherapy, 2 (17%) received anti-CTLA-4 monotherapy, and 2 (17%) received combination therapy. SM occurred after a median duration of 8.6 months from the first ICI dose. Most patients (75%) were asymptomatic on diagnosis. Three patients (25%) reported abdominal pain, nausea, and fever and received inpatient care and corticosteroid treatment with symptom resolution. No patients experienced SM recurrence after the completion of corticosteroids. Seven patients (58%) experienced resolution of SM on imaging. Seven patients (58%) resumed ICI therapy after the diagnosis of SM. Conclusions SM represents an immune-related adverse event that may occur after initiation of ICI therapy. The clinical significance and optimal management of SM following ICI therapy remains uncertain. While most cases were asymptomatic and did not require active management or ICI termination, medical intervention was needed in select symptomatic cases. Further large-scale studies are needed to clarify the association of SM with ICI therapy.