Long-lasting complete response of metastatic melanoma to ipilimumab with analysis of the resident immune cells

Abstract

Even though ipilimumab is a promising antibody used for stage IV melanoma therapy, the response varies and is difficult to predict. We here report on a case of successful treatment with ipilimumab in dacarbazine-resistant metastatic malignant melanoma, including a review of the literature on the long-term treatment results. A 62-year-old patient with a history of a resected lentigo-maligna melanoma 5 years earlier and parotideal metastasis 1 year before was admitted with a newly detected 3.5 cm liver metastasis. Atypical liver resection was performed (R1). Immunohistochemically, CD3+ T-lymphocytes and CD68+ macrophages were detected at the tumour margins and within the parotideal and hepatic melanoma metastases. A sub-analysis of the liver metastasis showed scattered FOX-P3+ regulatory T-lymphocytes as well as multiple CD8+ effector T-cells. Chemotherapy with dacarbazine 1,000 mg/m(2)/day was administered at 4-weeks intervals for 3 months. A follow-up positron-emission computed tomography and liver biopsy revealed melanoma metastases in the liver, lungs, and mediastinum. Compassionate use of ipilimumab was administered at 3 mg/kg every 3 weeks for a total of four doses. After an initial increase in tumour size, most lesions responded, but progressive axillary and cervical lymphadenopathy was observed before complete remission was achieved. Side effects included fatigue, dyspnoea, cough, upper abdominal pain with diarrhoea, and gingival hyperplasia. Now, 36 months after ipilimumab therapy and 8 years after the initial melanoma diagnosis, the tumour did not recur. It would be challenging to hypothesize that long intervals between diagnosis and need for treatment, clinical side effects, an initial increase in tumour size and the presence of intra-tumoural T-cells and macrophages might predict tumour response.

Long-Lasting Responses under Treatment with Ipilimumab: An Argument against Maintenance Therapy?

“…This could lead to the hypothesis that for a long-term response to immunotherapy a slow-growing tumor with low tumor load is essential. These hypotheses are also supported by other case reports implicating a correlation of long-term immunotherapy response in patients with long intervals between diagnosis and the need for treatment [9]. …”

Additional Clinical Value for PET/MRI in Oncology: Moving Beyond Simple Diagnosis

“…Preclinical studies indicate that dynamic 18 F-FDG PET may also distinguish between tumors with and without inflammation (23). If confirmed in clinical studies, this capability would suggest a potential role in predicting response to immune checkpoint inhibitor for which the presence of tumor-associated inflammation is considered to be associated with long-lasting response (24). Using PET/CT, derivation of these additional parameters would entail a significant extension of the examination time with a corresponding impact on workflows and cost.…”

C-kit expression in cancer cells or hematopoietic cells of the tumoral microenvironment: which is the basis for efficacy of TK inhibitors and immunotherapy in HCC?

“…Immunotherapy in solid tumors: from the beginning in 2010 to now in advanced HCC in cirrhosis After the intratumoral immune cell microenvironment directed attention of scientists toward HCC [50][51][52] , the therapeutic use of the so-called checkpoint inhibitors, also defined as immunotherapy, in patients with HCC in cirrhosis has matured [53] .…”