Nevertheless, a delay of almost 2?years between the first ipilimumab dose and the regression of in transit metastases would be highly unusual. involving a patient that received ipilimumab, a monoclonal antibody against cytotoxic T-lymphocyte associated protein 4 LNP023 (CTLA-4). CTLA-4 is a cell surface receptor that negatively regulates the immune response and its blockade can influence anti-tumor T cell activity. Ipilimumab showed a survival benefit in Phase III trials involving patients with advanced melanoma [1, 2]. Durable tumor responses in patients with advanced melanoma treated with ipilimumab yielded a plateau in the survival curve at 21% starting at 3?years from study initiation [3]. Here, we present a patient LNP023 with multifocal in-transit melanoma metastases who achieved spontaneous regression two years after completion of ipilimumab. Case presentation In October of 2012 an 84-year-old man with a history of coronary artery disease, COPD, hypertension, and venous insufficiency presented with multiple cutaneous nodules on his right leg. The lesions had been growing in size over the preceding 3?years (Fig. ?(Fig.1a).1a). An excisional biopsy was performed and revealed a malignant melanoma with focal necrosis. The lesion was described as purple, tender, 2.7??2.5??1.5?cm in size. A PET/CT of the entire body shown a dominant smooth cells mass lateral to the right fibular head with numerous additional soft cells nodules extending from the right mid thigh anteriorly to the level of the ankle, compatible with multiple cutaneous and subcutaneous melanoma metastases LNP023 (Fig. ?(Fig.1b).1b). There was no evidence for distant metastatic disease. BRAFV600 status was found to be wild-type. The patient was not deemed a candidate for hyperthermic isolated limb LNP023 perfusion due to peripheral vascular disease and the perceived very high risk for development of distant metastatic disease. Between December 2012 and February 2013 the patient received 4?cycles of the anti-CTLA-4 monoclonal antibody ipilimumab, at the standard dose of 3?mg/kg given once every 3?weeks, which he intially tolerated well except for intermittent low-grade diarrhea and fatigue. In April 2013, he developed anemia having a hemoglobin of 6.7?g/dl requiring transfusions. An extensive work up including bone marrow biopsy suggested real reddish cell aplasia, which is definitely rare however has been previously explained after treatment with CTLA-4 blockade [4], as the most likely etiology. The patient was treated having a pulse of dexamethasone for 4?days at 1?mg/kg-day, with no switch in his transfusion Fertirelin Acetate requirements and no rise of the reticulocyte count, then intravenous immunoglobulin (IVIg), with no reticulocytosis and no normalization of his hemoglobin. His cytogenetics showed 5/20 cells positive for del(5q), consistent with myelodysplastic syndrome and he consequently received a course of lenalidomide between April and June 2013, which was eventually halted 2nd to renal toxicity and considerable improvement of the anemia. His anemia was ultimately attributed to real reddish cell aplasia, which was caused by ipilimumab and resolved over a period of 6?weeks despite paperwork of 5q- myelodysplastic syndrome. Open in a separate windows Fig. 1 In transit metastases as evident clinically and on PET. a, b At baseline (October/November 2012). c, d Two years after the 2nd of 2 palliative medical resections (September 2016) Between December 2012 and December 2013 there was continued slow growth of the LNP023 right lower extremity metastases. By January 2014 accelerated progression of disease with considerable increase in the size of pre-existent ideal lower extremity pores and skin nodules as well as development of fresh nodules was mentioned. A nodule in the lateral right popliteal area enlarged to a size of ca. 4?cm over a few weeks and became ulcerated and chronically infected. The patient was not a candidate for a medical trial using PD-1/PD-L1 blockade. Given the lack of distant metastatic disease and the absence of persuasive systemic treatment options, in February 2014 a palliative resection of the fast growing dominating nodule was performed. The patient had a complicated postoperative program with wound dehiscence and repeating infections requiring intense wound care over a period of 3?weeks. During the protracted postoperative program there was further growth of multiple pores and skin metastases.