Cytokine release syndrome and immune effector cell­associated neurotoxicity syndrome in a melanoma patient treated with adjuvant pembrolizumab.

The emergence of immune checkpoint inhibitors (ICIs) has significantly improved the prognosis of patients with solid tumors. However, along with their efficacy, new toxicities related to immune system activation have surfaced, some of which pose life-threatening risks. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are among the serious, albeit rare, immune-related adverse effects (irAEs) observed. Although commonly associated with hematologic malignancies and chimeric antigen receptor T cell therapies, CRS has been reported in patients treated with ICIs, with ICANS being a less documented complication. The present study presents a case report of a 76-year-old patient with resected melanoma who developed clinical symptoms of CRS and ICANS following adjuvant pembrolizumab therapy. The patient presented with neurological symptoms of weakness and encephalopathy with confusion, bradypsychia, dysarthria, tremors and visual hallucinations. Laboratory tests revealed elevated serum levels of tumor necrosis factor-alpha and interleukin-6 along with inflammatory markers, hepatic and renal dysfunction, as well as rapidly progressive normochromic-normocytic anemia. Treatment with corticosteroids led to rapid symptom resolution, albeit with subsequent symptom recurrence after tapering its dose. This case underscores the importance of recognizing and managing irAEs associated with ICIs and highlights the need for vigilant monitoring and individualized therapeutic approaches.

Characteristics and outcomes of advanced melanoma patients with complete response and elective discontinuation of first-line anti-programmed death-1 monotherapy: A real-world multicentre observational cohort study.

Anti-programmed death-1 (anti-PD1) treatment has significantly improved outcomes of advanced melanoma with a considerable percentage of patients achieving complete response (CR). This real-world study analyzed the feasibility of elective anti-PD1 discontinuation in advanced melanoma patients with CR and evaluated factors related to sustained response. Thirty-five patients with advanced cutaneous or primary unknown melanoma with CR to nivolumab or pembrolizumab from 11 centers were included. Mean age was 66.5 years, and 97.1% had ECOG PS 0-1. 28.6% had ≥3 metastatic sites with 58.8% having M1a-M1b disease; 8.6% had liver and 5.7% had brain metastases. At baseline, 80% had normal LDH, and 85.7% had a neutrophil-to-lymphocyte ratio ≤3. 74.3% of patients had CR confirmed in PET-CT. Median duration of anti-PD1 was 23.4 months (range 1.3-50.5). 24 months after therapy discontinuation, 91.9% of patients were progression-free. Estimated PFS and OS at 36, 48, and 60 months from the start of anti-PD1 were 94.2%, 89.9%, 84.3%, and 97.1%, 93.3%, 93.3%, respectively. Antibiotics use after anti-PD1 discontinuation increased the odds of progression (OR 16.53 [95% CI 1.7, 226.03]). The study confirms the feasibility of elective anti-PD1 discontinuation in advanced melanoma patients with CR and favorable prognostic factors at baseline.

PD-L1 testing and clinical management of newly diagnosed metastatic non-small cell lung cancer in Spain: MOREL study.

AIM: To describe the clinical management and PD-L1 testing of patients with newly diagnosed stage IV non-small cell lung cancer (NSCLC) without driver mutations in Spain. METHODS: Multicenter, retrospective study. RESULTS: Among 297 evaluated patients, 89.2% received systemic treatment for stage IV disease, of whom 53.6% received platinum doublet therapy, 26.8% immunotherapy as monotherapy and 14.7% immunotherapy + chemotherapy, with 9.4% receiving treatment as part of a clinical trial. Treatment was initiated 1 month after histological diagnosis, with PD-L1 test results available in most cases (92.6%). PD-L1 testing was performed in 287 patients, 95.1% by in-house tests, mostly with the 22C3 pharmDx assay. The factor most strongly associated with treatment selection was, as expected, the expression of PD-L1. CONCLUSION: PD-L1 testing is implemented in clinical practice and seems to guide treatment decisions in patients with NSCLC in Spain.