A 46-year-old woman was diagnosed in 2013 with a choroid melanoma treated with plaque brachytherapy. A year later, metastatic disease in the liver was confirmed with biopsy and chemotherapy with Dacarbazine was administered. After three cycles, a computerized tomography (CT) evidence disease progression in the liver and therapy with the anti-CTLA4 antibody, Ipilimumab, was started (Dose: 3 mg/Kg. Total dose per cycle: 180 mg). One week after the fourth administration, the patient was remitted to our department because of generalized pruritus and cutaneous lesions on the lower limbs. Clinical examination revealed bilateral and symmetrical erythematous pretibial plaques and nodules (FIG. 1). Both lesions were biopsied, and pathology showed noncaseating granulomas in the dermis consistent with sarcoidosis (FIG. 2). Blood tests revealed an increased angiotensin-converting enzyme (107 U/L. Normal range, 8-52 U/L). The pretibial plaques were treated with topical clobetasol with a significant improvement. During radiological follow-up progression of the liver metastatic disease was detected and administration of Ipilimumab was stopped following the induction therapy, replacing the treatment.The patient is now participating in a new clinical trial. One month after discontinued Ipilimumab she reported progressive dyspnea. CT showed a new nodule on the right lower lobe and fibrous tracts and functional lung tests revealed severe decrease in carbon monoxide diffusing capacity (20% of predicted value). A bronchoscopy was normal and the broncho-alveolar lavage showed lymphocytosis with an inverted CD4:CD8 ratio (0.36). Although the CD4/CD8 ratio is usually high in pulmonary sarcoidosis, it was decided to initiate treatment with oral corticosteroids. After a few days the patient showed clinical improvement without relapse of dyspnea until now.
DiscussionIpilimumab is a humanized monoclonal antibody against cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) which has proved to increase survival in patients with metastatic melanoma (1). CTLA-4 is a negative regulator of T-cell activation so its blockade is thought to enhance an antitumor immune response. Its mechanism of action may be responsible for autoimmune adverse events like enterocolitis, hypophysitis, dermatitis, uveitis, vitiligo, arthritis, or hepatitis. A recent systematic review and meta-analysis tried to assess the incidence and nature of immune related adverse events associated with anti-CTLA-
Central nervous system (CNS) dissemination is a severe complication in cancer and a leading cause of cancer-related mortality. Brain metastases (BMs) are the most common types of malignant intracranial tumors and are reported in approximately 25% of patients with metastatic cancers. The recent increase in incidence of BMs is due to several factors including better diagnostic assessments and the development of improved systemic therapies that have lower activity on the CNS. However, newer systemic therapies are being developed that can cross the blood–brain barrier giving us additional tools to treat BMs. The guidelines presented here focus on the efficacy of new targeted systemic therapies and immunotherapies on CNS BMs from breast, melanoma, and lung cancers.
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