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 E, a 67-year-old woman, underwent resection of an acrolentiginous melanoma from the sole of her right foot in March 2008, at which time she had a positive popliteal and inguinal sentinel-node biopsy. In May 2008, a popliteal-inguinal-crural and ilio-obturator right lymphadenectomy was performed and melanoma metastases were found in two additional lymph nodes. In August 2008, she was recruited into a phase 1 pilot clinical trial of intradermal autologous mRNA electroporated dendritic cells (TriMix-DC) and additional interferon-alpha-2b (5 MU subcutaneously 3 times weekly) but on February 20, 2009; she had further unresectable in-transit metastases in her right leg. On May 6, 2009; patient E underwent limb perfusion with melphalan, tumor necrosis factor-alpha and interferon-gamma and on May 28, 2009; she had a PR of the in-transit metastases in her right leg by both mWHO response criteria and RECIST. In November 2009, however, this patient had PD with in-transit metastases in her right leg () and inguinal and peri-iliacal lymph node metastases. She was started on chemotherapy with dacarbazine on March 15, 2010 but in May 2010, after three cycles of chemotherapy, she had PD.\nOn June 11, 2010; Patient E started ipilimumab 3 mg/kg in the EAP. During the first weeks of ipilimumab treatment, there was an increase in size and number of the in-transit metastases in her right leg (). From Week 8, there was a slow regression of the in-transit metastases that resulted in complete disappearance at 1 year (). Patient E had a modest increase of her absolute lymphocyte count during ipilimumab treatment (from 1,648/mm3 at baseline to 2,052/mm3 at the 4th ipilimumab dose). Meanwhile, PET-CT imaging in February 2011, 34 weeks after starting ipilimumab, showed PD of the inguinal and peri-iliacal lymph nodes and the patient started retreatment therapy with ipilimumab 3 mg/kg on February 21. A repeat assessment 10 weeks after retreatment showed a regression of the metastatic lymph nodes which qualified for SD by all tumor response criteria, but with a marked regression (33% decrease by mWHO criteria). A second assessment in Week 26 after retreatment showed a further regression of the inguinal and peri-iliacal lymph nodes, which was classified as a PR according to both mWHO criteria and RECIST. She had no adverse-events during ipilimumab treatment. At further follow-up in November 2011 (Week 38 after retreatment), progressive disease of the iliacal lymph nodes and new in-transit metastases in the right leg were documented and the patient was subsequently treated with a selective BRAF-inhibitor (vemurafenib).