Immunotherapy around the Clock: Impact of Infusion Timing on Stage IV Melanoma Outcomes.

Although the impact of circadian timing on immunotherapy has yet to be integrated into clinical practice, chronoimmunotherapy is an emerging and promising field as circadian oscillations are observed in immune cell numbers as well as the expression of immunotherapy targets, e.g., programmed cell death protein-1 and its ligand programmed death ligand 1. Concurrent retrospective studies suggest that morning infusions may lead to higher effectiveness of immune checkpoint inhibitors in melanoma, non-small cell lung cancer, and kidney cancer. This paper discusses the results of a retrospective study (2016-2022) exploring the impact of infusion timing on the outcomes of all 73 patients with stage IV melanoma receiving immunotherapy at a particular medical center. While the median overall survival (OS) was 24.2 months (95% confidence interval [CI] 9.04-39.8), for a median follow-up of 15.3 months, our results show that having more than 75% of infusions in the afternoon results in shorter median OS (14.9 vs. 38.1 months; hazard ratio 0.45 [CI 0.23-0.86]; p < 0.01) with more expressive impacts on particular subgroups: women, older patients, and patients with a lower tumor burden at the outset of immunotherapy. Our findings highlight the potential benefits of follow-up validation in prospective and translational randomized studies.

Immunotherapy in Metastatic Mucosal Melanoma with Disseminated Intravascular Coagulation: A Case of Success.

Mucosal melanoma accounts for 1% of all melanomas. It is more aggressive than cutaneous melanoma, and local excision provides the best disease-free survival. The vast majority of patients eventually develop metastases, with a metastatic pattern independent of the primary tumor site. While studies show that BRAF and KIT inhibitors have a role in the management of these patients, the actual treatment focus is on immunotherapy. Herein is described the case of a 79-year-old woman with metastatic mucosal melanoma and bone marrow infiltration causing disseminated intravascular coagulation, who was treated with an immunotherapy combination (anti-CTLA-4 and anti-PD-1 antibodies), achieving complete disease remission. This is the third case of melanoma with disseminated intravascular coagulation at presentation and the second case treated with immunotherapy in the literature, but the only one achieving disease remission.

BRAF L597K mutation: an opportunity to treat.

The outcomes of patients with metastatic melanoma (MM) have significantly improved after the introduction of BRAF-specific inhibitors. Herein is reported a patient with MM and non-V600-BRAF mutation who responded to iBRAF/iMEK therapy. In July 2014, a 63-year-old man presented with a 4.1mm-thick V600E-BRAF wild type melanoma on the back. Metastases were identified in one sentinel node and two of 11 subsequently excised lymph nodes, with no signs of distant metastatic disease. In September 2017, lung metastasis was observed and pembrolizumab was started. Progressive disease was apparent at cycle 10 and therapy was switched to ipilimumab. After four cycles, an asymmetric response was observed. In November 2017, next generation sequencing genomic profiling disclosed a rare L597K-BRAF mutation and vemurafenib plus cobimetinib therapy was initiated in January 2018. Seven days after treatment start, a remarkable clinical improvement was observed. In April 2018, the patient achieved partial response, which was sustained until October 2018. Cases of patients with non-V600-BRAF mutations responding to iBRAF/iMEK therapy have been reported over the last years. To the best of our knowledge, this is the first case reporting response to combined iBRAF/iMEK therapy in a patient with metastatic melanoma harboring L597K mutation.