Since the approval of pembrolizumab and nivolumab, antibodies against programmed cell death 1 (PD-1) receptor, for several types of cancer, immune-related adverse events (irAE) keep treating physicians concerned [1, 2]. The underlying mechanism of irAE is the reactivity of immune system against normal tissue.
Limitations in predicting PAM50 intrinsic subtype and risk of relapse score with Ki67 in estrogen receptor-positive HER2-negative breast cancer Limitations in predicting PAM50 intrinsic subtype and risk of relapse score with Ki67 in estrogen receptor-positive HER2-negative breast cancer
The treatment landscape for advanced melanoma has transformed significantly with the advent of BRAF and MEK inhibitors (BRAF/MEKi) targeting BRAFV600 mutations, as well as immune checkpoint inhibitors (ICI) like anti-PD-1 monotherapy or its combinations with anti-CTLA-4 or anti-LAG-3. Despite that, many patients still do not benefit from these treatments at all or develop resistance mechanisms. Therefore, prognostic and predictive biomarkers are needed to identify patients who should switch or escalate their treatment strategies or initiate an intensive follow-up. In melanoma, liquid biopsy has shown promising results, with a potential role in predicting relapse in resected high-risk patients or in disease monitoring during the treatment of advanced disease. Several components in peripheral blood have been analyzed, such as circulating tumor cells (CTCs), cell-free DNA (cfDNA), and circulant tumoral DNA (ctDNA), which have turned out to be particularly promising. To analyze ctDNA in blood, different techniques have proven to be useful, including digital droplet polymerase chain reaction (ddPCR) to detect specific mutations and, more recently, next-generation sequencing (NGS) techniques, which allow analyzing a broader repertoire of the mutation landscape of each patient. In this review, our goal is to update the current understanding of liquid biopsy, focusing on the use of ctDNA as a biological material in the daily clinical management of melanoma patients, in particular those with advanced disease treated with ICI.
Aim: While both efficacy and safety of anti-PD-1 agents seem to be independent of previous treatment with anti-CTLA-4, limited data exist of efficacy and toxicity of ipilimumab after progression on anti-PD-1 therapy. This retrospective analysis describes the efficacy and safety of sequential therapy with ipilimumab in patients with metastatic melanoma who progressed on anti-PD-1 antibody. Methods: Nine patients who progressed on anti-PD-1 therapy received four cycles of ipilimumab 3 mg/kg every 3 weeks. Results: Two out of nine patients (2/9; 22.2%) showed a partial response, and seven patients (7/9; 77.8%) experienced disease progression. Median progression-free survival was 3.14 months (95% CI: 2.56–3.71), and the median overall survival since the start of anti-PD-1 therapy was 16.8 months (95% CI: 8.1–25.4). Five (5/9; 55.6%) patients experienced grade 3 immune-related adverse events. No grade 4 or 5 adverse events were reported. Conclusion: In this small retrospective series of cases, the efficacy of ...
Diabetes is a rare, but potentially life‐threatening, adverse event of immune checkpoint inhibitors that requires prompt recognition and treatment. It usually occurs in the first 3 months of treatment and is typically related to programmed cell death‐1 antibodies, alone or in combined therapy. It has rarely been described developing after immunotherapy cessation. We present a 51‐year‐old man with metastatic melanoma, who developed acute‐onset diabetes 52 days after combined immunotherapy cessation with nivolumab and ipilimumab, and 25.6 months after receiving the first dose. He presented with acute hyperglycemic symptoms, ketosis, complete insulin depletion and negative autoimmunity, fulfilling the criteria of fulminant type 1 diabetes. The patient had previously developed hypophysitis with isolated adrenocorticotropic hormone deficiency during immunotherapy. We describe a case of late‐onset fulminant type 1 diabetes developing after immunotherapy cessation. Patient education and active follow up after immunotherapy discontinuation are crucial to warrant a timely intervention.