Meningeal melanomatosis following discontinuation of dabrafenib: implications for the maintenance of long-term complete remission.

A subset of 10-20% of patients under continuous BRAF inhibitor monotherapy achieve long-term progression-free and overall survival. Definitive criteria for the safe cessation of BRAF inhibitor monotherapy in treatment-responsive melanoma patients are lacking. We report a patient who remained in complete remission (CR) for 5 years under dabrafenib. The treatment was withdrawn because of concerns about cardiac toxicity. Four months thereafter the patient developed neurological symptoms, including diplopia and bilateral visual loss. Meningeal melanomatosis and parenchymal brain metastases were diagnosed. Extracerebral metastases were excluded. Reinduction of dabrafenib, combined with trametinib, led to the rapid relief of the neurological symptoms, and a partial remission was confirmed radiologically. Unfortunately, the response was not maintained and the patient died 9 months later. This observation demonstrates that discontinuation of BRAF inhibition can result in loss of disease control. On the basis of this observation, we suggest that BRAF-targeted therapy should be withdrawn only when the risks of continued treatment exceed the risk for disease relapse. However, future studies are urgently required to confirm and quantify the risk for rapid disease relapse following withdrawal of BRAF inhibitor monotherapy.

Correlation of Serum Levels of IgE Autoantibodies Against BP180 With Bullous Pemphigoid Disease Activity.

Importance: Bullous pemphigoid (BP) is by far the most frequent autoimmune blistering disease. The presence of IgE autoantibodies against the transmembrane protein BP antigen 2 (BP180, type XVII collagen) has previously been reported in 22% to 100% of BP serum samples, and the pathogenic relevance of anti-BP180 IgE has been suggested in various experimental models and by the successful use of omalizumab in individual patients with BP. Objectives: To determine the rate of anti-BP180-reactive IgE in BP, to evaluate the diagnostic relevance of anti-BP180 IgE in BP, and to correlate anti-BP180 IgE with disease activity and the clinical phenotype of patients with BP. Design, Setting, and Participants: This case-control cohort study examined 3 groups of patients with BP. Sixty-five patients with BP underwent an enzyme-linked immunosorbent assay for IgE antibodies against the 16th noncollagenous domain of BP180 (NC16A); 52 consecutive patients with BP underwent clinical evaluation with the Bullous Pemphigoid Disease Activity Index (BPDAI); and 36 patients with BP without anti-BP180 NC16A IgG reactivity underwent evaluation of the diagnostic importance of serum anti-BP180 IgE. In addition, 49 age-matched control individuals with noninflammatory dermatoses, 127 controls undergoing allergy testing for IgE levels, and 30 controls with pemphigus vulgaris or pemphigus foliaceus were included for comparison. Patients were seen at a university clinic from January 1, 2008, to July 31, 2014. Main Outcomes and Measures: Serum anti-BP180 NC16A IgE and IgG levels and BPDAI scores. Results: Of 117 patients with BP (69 women and 48 men), anti-BP180 NC16A serum IgE was detected in 47 (40.2%) and correlated with disease activity as measured by total BPDAI (r = 0.918; P = .06). An intraindividual correlation of anti-BP180 NC16A serum levels with the total BPDAI was observed during the course of the disease in 10 randomly selected patients with BP (r = 0.983; P = .003). Although no association of circulating BP180 NC16A IgE antibodies with urticarial or erythematous lesions was observed (r = 0.481; P = .31), the presence of IgG anti-BP180 NC16A antibodies was associated with the occurrence of erosions and blisters (r = 0.985; P = .006) but not urticarial and erythematous lesions (r = 0.632; P = .23). Assaying for anti-BP180 IgE increased the diagnostic sensitivity by only 2.2% (1 of 46 serum samples) when combined with the IgG anti-BP180 enzyme-linked immunosorbent assay. Conclusions and Relevance: Although detection of serum anti-BP180 IgE is not of diagnostic importance, it may be relevant for therapeutic decisions (eg, the use of anti-IgE treatment). The correlation of serum anti-BP180 NC16A IgE levels with disease activity in patients with BP supports the notion that anti-BP180 IgE is of pathogenic relevance. Our observation that IgG anti-BP180 antibodies are related to the occurrence of blisters and erosions may encourage further studies on the association of fine autoantibody reactivities with clinical features of BP.

Rapid remission of symptomatic brain metastases in melanoma by programmed-death-receptor-1 inhibition.

Although ∼40% of patients with metastatic melanoma develop brain metastases, the presence of brain metastases often precludes enrolment in clinical trials for advanced melanoma. However, the development of symptomatic brain metastases markedly increases mortality. The antiprogrammed-death-receptor-1 antibody pembrolizumab achieves extracranial metastases disease response rates of up to 50%. Here, we report the rapid and sustained response of symptomatic multifocal brain metastases in a melanoma ipilimumab-pretreated patient under pembrolizumab, combined with high-dose dexamethasone therapy during the induction phase of therapy. Complete remission has been maintained for over 1 year of follow-up and has correlated with the response rate observed in the extracranial metastases. Radiological disease response was identified during the first follow-up visit in the absence of adjuvant radiotherapy. This report highlights the need for further clinical studies to specifically address the therapeutic potential of antiprogrammed-death-receptor-1 monotherapy in the management of untreated brain metastases in melanoma.