Management of infliximab refractory immune checkpoint inhibitor gastrointestinal toxicity: a multicenter case series.
Abstract Background: Immune checkpoint inhibitor (ICI) gastrointestinal toxicity (gastritis, enteritis, colitis) is a major cause of morbidity and treatment-related death. Guidelines agree steroid-refractory cases warrant infliximab, however best management of infliximab-refractory ICI gastrointestinal toxicity (IRIGItox) is unknown. Methods: We conducted an international multicenter retrospective case series. IRIGItox was defined as failure of symptom resolution ≤grade 1 (Common Terminology Criteria for Adverse Events V.5.0) following ≥2 infliximab doses or failure of symptom resolution ≤grade 2 after one dose. Data were extracted regarding demographics, steroid use, response to treatment, and survival outcomes. Toxicity was graded at symptom onset and time of infliximab failure. [...]
Rethinking the urgency priority system in round hole detachments, which should be done first? Macula on or macula off.
No abstract available. Read Full Paper
Efficacy and safety of ‘Second Adjuvant’ therapy with BRAF/MEK inhibitors after local therapy for recurrent melanoma following adjuvant PD-1 based immunotherapy.
Abstract Background: Anti-PD-1 antibodies and BRAK/MEK inhibitors (BRAF/MEKi) reduce the risk of recurrence for patients with resected stage III melanoma. BRAFV600-mutated (BRAFmut) melanoma patients who recur with isolated disease following adjuvant therapy may be suitable for 'second adjuvant' treatment after local therapy. We sought to examine the efficacy and safety of 'second adjuvant' BRAF/MEKi. Patients and methods: Patients with BRAFmut melanoma treated with adjuvant PD-1 based immunotherapy who recurred, underwent definitive local therapy and were then treated with adjuvant BRAF/MEKi were identified retrospectively from 13 centres (second adjuvant group). Demographics, disease and treatment characteristics and outcome data were examined. Outcomes were [...]
Combined immunotherapy in melanoma patients with brain metastases: A multicenter international study.
Abstract Background: Ipilimumab plus nivolumab (COMBO) is the standard treatment in asymptomatic patients with melanoma brain metastases (MBM). We report a retrospective study aiming to assess the outcome of patients with MBM treated with COMBO outside clinical trials. Methods: Consecutive patients treated with COMBO have been included. Demographics, steroid treatment, Central Nervous System (CNS)-related symptoms, BRAF status, radiotherapy or surgery, response rate (RR), progression-free (PFS) and overall survival (OS) have been analyzed. Results: 376 patients were included: 262 received COMBO as first-line and 114 as a subsequent line of therapy, respectively. In multivariate analysis, Eastern Cooperative Oncology Group (ECOG) (≥1 vs 0) [...]
Safety profile of pembrolizumab monotherapy based on an aggregate safety evaluation of 8937 patients.
Abstract Background: Pembrolizumab has a manageable safety profile as described in its label, which was primarily based on 2799 patients who participated in clinical trials for melanoma or non-small cell lung cancer. Here, we evaluated the safety of pembrolizumab in a broader population of patients from 31 advanced cancer clinical trials across 19 cancer types. Methods: Safety was analyzed in patients who received at least one dose of pembrolizumab (200 mg every 3 weeks [Q3W], 10 mg/kg Q2W or Q3W, or 2 mg/kg Q3W). Adverse events (AEs) and immune-mediated AEs and infusion reactions were evaluated. Results: Safety data from 8937 patients in [...]
Author Correction: Adjuvant nivolumab in resected stage IIB/C melanoma: primary results from the randomized, phase 3 CheckMate 76K trial.
No abstract available. Read Full Paper
Seasonal patterns of toxicity in melanoma patients treated with combination anti-PD-1 and anti-CTLA-4 immunotherapy.
Abstract Background: Immune checkpoint inhibitors are frequently associated with the development of immunotherapy-related adverse events (irAEs). The exact etiology, including the role of environmental factors, remains incompletely understood. Methods: We analyzed the records of 394 melanoma patients from three centers (northern and southern hemisphere). Patients had received at least one cycle of anti-PD-1/anti-CTLA-4 with a minimum follow-up of 3 months. We study the distribution and time to irAEs onset throughout the calendar year. Results: 764 irAEs were recorded; the most frequent were skin rash (35%), hepatitis (32%) and colitis (30%). The irAEs incidence was the highest in autumn and winter, and the [...]
The side effect registry immuno-oncology (SERIO) – A tool for systematic analysis of immunotherapy-induced side effects.
Abstract Background: Immunotherapies such as immune checkpoint inhibitors (ICI) are effective in multiple tumor entities but induce a plethora of side effects. Comprehensive real-world analyses are essential to identify new signals, characterize diagnostic features, enable risk assessment, determine pathomechanisms, assess effectiveness of side effect management and compare tumor outcomes. Methods: The international online `Side-Effect Registry Immuno-Oncology´ (SERIO; www.serio-registry.org) collects rare, complex, and severe immunotherapy-induced side effects across all tumor entities with a strong focus on ICI-induced immune-related adverse events (irAE). The relational database management system (RDMS) contains structured data on patient and tumor characteristics, type of immunotherapy, treatment of side effects, [...]
Prognostic and predictive biomarkers in melanoma.
Abstract Biomarkers help to inform the clinical management of patients with melanoma. For patients with clinically localised primary melanoma, biomarkers can help to predict post-surgical outcome (including via the use of risk prediction tools), better select patients for sentinel lymph node biopsy, and tailor catch-all follow-up protocols to the individual. Systemic drug treatments, including immune checkpoint inhibitor (ICI) therapies and BRAF-targeted therapies, have radically improved the prognosis of metastatic (stage III and IV) cutaneous melanoma patients, and also shown benefit in the earlier setting of stage IIB/C primary melanoma. Unfortunately, a response is far from guaranteed. Here, we review [...]
Pembrolizumab versus placebo as adjuvant therapy in resected stage IIB or IIC melanoma: Outcomes in histopathologic subgroups from the randomized, double-blind, phase 3 KEYNOTE-716 trial.
Abstract Background: Adjuvant pembrolizumab significantly improved recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) versus placebo in the phase 3 KEYNOTE-716 study of resected stage IIB or IIC melanoma. At the prespecified third interim analysis (data cut-off, January 4, 2022), the HR for RFS in the overall population was 0.64 (95% CI, 0.50 to 0.84) and the HR for DMFS was 0.64 (95% CI, 0.47 to 0.88). We present a post hoc analysis of efficacy by subtypes defined by histopathologic characteristics. Methods: Patients aged ≥12 years with newly diagnosed, resected stage IIB or IIC melanoma were randomly assigned (1:1) to pembrolizumab [...]