Ipilimumab in patients with melanoma and autoimmune disease

Abstract

Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4), an immune-checkpoint receptor and regulator of T-cell activation, has become an important therapeutic target for immunotherapy in cancer and autoimmune diseases. To date, clinical trials involving cancer immunotherapies, such checkpoint blocking antibodies directed at CTLA-4 (ipilimumab), have excluded patients with underlying autoimmune disease given concern for potential triggering of autoimmune exacerbations. We present the first known cases to our knowledge of two patients with active autoimmune diseases who received ipilimumab. In this limited clinical experience, no serious exacerbations of underlying autoimmunity have yet been observed, and one patient benefited from ipilimumab. These cases advocate for further investigation of the safety of cancer immunotherapies in cancer patients with underlying autoimmune conditions in carefully designed clinical trials with cautious monitoring.

Keywords: Autoimmune diseases; Immune-related adverse events (irAEs); Immunotherapy; Ipilimumab; Melanoma; Multiple sclerosis; Rheumatoid arthritis.

Figure 1

Timeline of treatment and demonstration of response. (a) Baseline chest CT scan prior to ipilimumab showed multiple subcutaneous, intramuscular, and pulmonary nodules (largest nodule indicated by white arrow). (b) Two months after completion of four treatments with ipilimumab, restaging PET scan showed decreased size of lung nodules, soft tissue and osseous involvement. (c) Repeat CT scan showed near radiographic resolution of lung nodule. (d) Timeline of described events (not to scale).