Immunotherapy use outside clinical trial populations: never say never?
Abstract Background: Based on favourable outcomes in clinical trials, immune checkpoint inhibitors (ICIs), most notably programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte antigen-4 (CTLA-4) inhibitors, are now widely used across multiple cancer types. However, due to their strict inclusion and exclusion criteria, clinical studies often do not address challenges presented by non-trial populations. Design: This review summarises available data on the efficacy and safety of ICIs in trial-ineligible patients, including those with autoimmune disease, chronic viral infections, organ transplants, organ dysfunction, poor performance status, and brain metastases, as well as the elderly, children, and those who are pregnant. In [...]
Novel adjuvant options for cutaneous melanoma.
Abstract Background: Patients with resected stage III and IV melanoma have a high risk of recurrence. As the outcomes for patients with metastatic disease have improved dramatically over the past decade due to systemic therapy, more recently so too have the outcomes of patients with resected stage III and IV melanoma with the introduction of checkpoint inhibitor immunotherapy and targeted therapy in the adjuvant setting. Materials and methods: This review outlines the latest clinical trial data, the current adjuvant treatment landscape and its application to clinical practice and expected future progress for the management of early-stage melanoma. Results: Anti-programmed cell death protein [...]
Recent advancements in melanoma management.
Abstract The treatment options for patients with melanoma have expanded significantly over the past decade. In particular, the use of targeted therapy and immunotherapy has dramatically transformed the outlook for patients with advanced disease. These treatments are now being utilised as adjuvant therapy for patients with earlier stage melanoma after surgical resection. We review the latest updates for melanoma staging, surgical resection, radiotherapy and systemic therapies. Read Full Paper
Pathological response and tumour bed histopathological features correlate with survival following neoadjuvant immunotherapy in stage III melanoma.
Abstract Background: Guidelines for pathological evaluation of neoadjuvant specimens and pathological response categories have been developed by the International Neoadjuvant Melanoma Consortium (INMC). As part of the Optimal Neo-adjuvant Combination Scheme of Ipilimumab and Nivolumab (OpACIN-neo) clinical trial of neoadjuvant combination anti-programmed cell death protein 1/anti-cytotoxic T-lymphocyte-associated protein 4 immunotherapy for stage III melanoma, we sought to determine interobserver reproducibility of INMC histopathological assessment principles, identify specific tumour bed histopathological features of immunotherapeutic response that correlated with recurrence and relapse-free survival (RFS) and evaluate proposed INMC pathological response categories for predicting recurrence and RFS. Patients and methods: Clinicopathological characteristics of lymph [...]
Outcome of melanoma patients with elevated LDH treated with first-line targeted therapy or PD-1-based immune checkpoint inhibition.
Abstract Background: Elevated lactate dehydrogenase (LDH) is a known predictive and prognostic factor for a poor outcome in patients with metastatic melanoma. It is unclear whether first-line targeted therapy (TT) or immune checkpoint inhibition (ICI) is more beneficial in melanoma patients with elevated LDH because prospective studies in this area are lacking. Methods: This multicentre retrospective cohort study was conducted at 25 melanoma centres worldwide to analyse progression-free survival (PFS) and overall survival (OS) among melanoma patients with elevated LDH. The role of confounders was addressed by using inverse probability of treatment weighting. Results: Among 173 BRAFV600-mutant patients, PFS at 12 months [...]
Hematological immune related adverse events after treatment with immune checkpoint inhibitors.
Abstract Introduction: With the increasing use of checkpoint inhibitors, rare immune-related adverse events (irAE) are being identified. Haematological irAE (hem-irAE) are difficult to treat and have shown high mortality rates. In order to improve side-effect management for these potentially life-threatening events, we analysed frequency, severity and outcomes. Patients and methods: Patients who developed hem-irAE while being treated with immune checkpoint inhibitors (ICI) therapy were retrospectively identified from 18 international cancer centres. Results: In total, more than 7626 patients treated with ICI were screened, and 50 patients with hem-irAE identified. The calculated incidence amounts to 0.6% and median onset was 6 weeks after [...]
Efficiency of Detecting New Primary Melanoma Among Individuals Treated in a High-risk Clinic for Skin Surveillance.
Abstract Importance: A previous single-center study observed fewer excisions, lower health care costs, thinner melanomas, and better quality of life when surveillance of high-risk patients was conducted in a melanoma dermatology clinic with a structured surveillance protocol involving full-body examinations every 6 months aided by total-body photography (TBP) and sequential digital dermoscopy imaging (SDDI). Objective: To examine longer-term sustainability and expansion of the surveillance program to numerous practices, including a primary care skin cancer clinic setting. Design, setting, and participants: This prospective cohort study recruited 593 participants assessed from 2012 to 2018 as having very high risk of melanoma, with a median [...]
Pathological response and survival with neoadjuvant therapy in melanoma: a pooled analysis from the International Neoadjuvant Melanoma Consortium (INMC)
Alexander M. Menzies, Rodabe N. Amaria, Elisa A. Rozeman, Alexander C. Huang, Michael T. Tetzlaff, Bart A. van de Wiel, Serigne Lo, Ahmad A. Tarhini, Elizabeth M. Burton, Thomas E. Pennington, Robyn P. M. Saw, Xiaowei Xu, Giorgos C. Karakousis, Paolo A. Ascierto, Andrew J. Spillane, Alexander C. J. van Akkooi, Michael A. Davies, Tara C. Mitchell, Hussein A. Tawbi, Richard A. Scolyer, Jennifer A. Wargo, Christian U. Blank & Georgina V. Long. Nat Med (2021).
Survival and biomarker analyses from the OpACIN-neo and OpACIN neoadjuvant immunotherapy trials in stage III melanoma.
Abstract Neoadjuvant ipilimumab plus nivolumab showed high pathologic response rates (pRRs) in patients with macroscopic stage III melanoma in the phase 1b OpACIN ( NCT02437279 ) and phase 2 OpACIN-neo ( NCT02977052 ) studies1,2. While the results are promising, data on the durability of these pathologic responses and baseline biomarkers for response and survival were lacking. After a median follow-up of 4 years, none of the patients with a pathologic response (n = 7/9 patients) in the OpACIN study had relapsed. In OpACIN-neo (n = 86), the 2-year estimated relapse-free survival was 84% for all patients, 97% for patients achieving a pathologic response [...]