Patterns of Response in Patients with Pretreated Metastatic Melanoma who Received Ipilimumab 3 mg/kg in a European Expanded Access Program: Five Illustrative Case Reports
Patient A was a 45-year-old man who had a successful excision of a primary melanoma on his back at which time he had no signs of locoregional or distant metastases, but who developed brain metastasis 5.5 years later, in February 2010. There were no sites of extracranial metastases. Adjuvant pancranial radiotherapy was administered. In March 2010, total body 18FDG-PET/CT scans revealed the appearance of 18FDG-avid lymph node, muscle, and lung metastases. First-line chemotherapy with dacarbazine was initiated. In July 2010, after three cycles of dacarbazine, repeat assessment showed PD of lymph node, muscle, lung, small intestine, and bone. There was no progression of disease within the CNS.\nIn August 2010 following referral to our hospital, Patient A provided signed informed consent for treatment with second-line ipilimumab 3 mg/kg every 3 weeks by intravenous infusion for a total of four doses in a European EAP. He had a baseline WHO PS of 1 and baseline laboratory tests showed a LDH level below the upper limit of normal (ULN) and slightly elevated C-reactive protein at 2 × ULN. Organ functions were normal. After his first dose of ipilimumab, he concomitantly received radiotherapy (30 Gy) for a symptomatic bone metastasis to the right knee. During ipilimumab treatment (every 3 weeks, for a total of 4 administrations), Patient A experienced grade 1 diarrhoea that resolved within 24 hr following therapy with loperamide, and grade 2 pruritus successfully palliated with a single 10 mg oral dose of cetirizine. At his first tumor response assessment at Week 12, Patient A had a documented PR by mWHO criteria. Only one muscular metastasis in the upper left leg, the irradiated skeletal metastasis in the right knee and a smaller bone metastasis in the right tibia remained 18FDG-avid; all other lesions had decreased significantly in size and had become 18FDG-negative (Figure ). An MRI of the brain confirmed that there was no progression in the CNS. There was also a marked increase in absolute lymphocyte count (ALC) compared to the baseline value (2371 vs. 1181/mm3, respectively).\nTumor assessment at Week 24, in February 2011, confirmed the patient's PR, with complete disappearance of all muscular metastases. The bone metastasis in the right knee (which had been irradiated during treatment with ipilimumab) had also become 18FDG-negative (Figure ). A single metastasis to the right tibia had become more prominent on 18FDG-imaging; therefore a decision was taken to administer focal radiotherapy (30 Gy) to this residual solitary metastatic site. At Week 38, in May 2011, Patient A had reappearance of metastatic mediastinal lymph nodes but he remained asymptomatic with normal blood values and without progression in the CNS. He was given retreatment with ipilimumab and at repeat assessment in early August 2011, he was showing a stabilization of the mediastinal metastatic lymph nodes and the tibial bone metastasis. Mutation analysis of the patient's tumor material demonstrated the presence of a BRAFV600E mutation and the patient subsequently initiated treatment with a BRAF inhibitor in September 2011.