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
A 61-year-old man (Patient D) had presented with an acral ulcerated melanoma on the third toe of his left foot in January 2009. In February, the affected toe was surgically removed and a sentinel node biopsy showed evidence of metastasis. The following month, a left iliaco-inguinal lymphadenectomy did not show any additional metastatic nodes and the final pathologic staging was pT4bN1Mx. One year and 2 months later, in April 2010, follow-up PET-CT scans revealed stage IV-M1c disease with liver, lymph node and subcutaneous metastases. Patient D started first-line dacarbazine (1 g/m2 every 3 weeks) in July of 2010 but on August 20, after two cycles of chemotherapy, he was assessed as having PD (by RECIST criteria).\nBetween August 27 and October 29, 2010 Patient D received ipilimumab 3 mg/kg in a European EAP. At baseline he had 18FDG-avid metastases in the liver, para-iliac lymph node and distally in the inner left upper leg (Figure ). At Patient D's first evaluation in Week 12, he had regression of the liver metastasis but increases in both the dimensions and 18FDG uptake in the para-iliac and inner left upper leg distal lesions. There was also the appearance of a new iliaco-femoral lymph node metastasis. This corresponded to an assessment of PD by mWHO criteria or RECIST, but qualified for SD by irRC. Evaluation in Week 24 showed further regression of the liver metastasis and regression of the para-iliac metastasis and distal metastasis in the left leg accompanied by complete loss of 18FDG uptake. At the same time, there was an increase in size and 18FDG uptake in the iliaco-femoral lymph node metastasis and the appearance of a new proximal lesion in the inner left upper leg. Although the patient still had PD by conventional response criteria, he now qualified for a PR by irRC. Before the start of retreatment, this patient had near-complete regression of the liver and para-iliac metastases but further progression of the iliaco-femoral, inner left upper leg distal and inner left upper leg proximal lesions (Figure ). His ALC increased after treatment peaking at approximately 3,000/mm3 at Week 20.\nPatient D had normal blood values prior to and during ipilimumab treatment but did experience grade 1 pruritus, treated with oral antihistamines. After the end of ipilimumab therapy, he developed vitiligo of the face. Retreatment therapy with ipilimumab 3 mg/kg was started on July 8, 2011. At his first evaluation after retreatment (September 27, 2011), all lesions further regressed in size, with a complete loss of 18FDG uptake. The patient's clinical status (Karnofsky PS score = 100%) and laboratory values remained normal throughout treatment with ipilimumab.