Information about Pembrolizumab
Pembrolizumab is a humanized monoclonal antibody to programmed cell death receptor 1 (PD-1), which results in an increased immune reactivity that can break tolerance and is used in the immunotherapy of cancer.
Liver safety of Pembrolizumab
Pembrolizumab therapy has many adverse events and particularly immune related conditions, including acute hepatitis and acute liver injury which can be serious and even life threatening.
Mechanism of action of Pembrolizumab
Pembrolizumab (pem" broe liz' ue mab) is a humanized recombinant monoclonal IgG4 kappa-isotype antibody to the programmed cell death receptor-1 (PD-1) which has distinctive immunomodulatory activity and is used in cancer immunotherapy. PD-1 is an important check point molecule that modulates and down regulates T cell responses. Inhibition of PD-1 receptors on the surface of activated T cells prevents their binding to the PD ligand which ordinarily terminates the activation and proliferation of T cells. Without the PD-1 receptor engagement, T cell responses remained activated. The subsequent enhancement of cytotoxic reactivity may play a beneficial role in cancer immunotherapy by breaking immunological tolerance to cancer cell neo-antigens. In several large multicenter studies, pembrolizumab therapy resulted in a prolongation of survival in patients with advanced, metastatic or unresectable malignant melanoma, and a proportion of patients had a long term remission.
FDA approval information for Pembrolizumab
Pembrolizumab was approved for use in advanced melanoma in the United States in 2014 and for advanced non-small cell lung cancer (NSCLC) in 2015. It is also under active investigation in several other forms of cancer, including breast and renal cancer and lymphomas.
Side effects of Pembrolizumab
Pembrolizumab is available in single use vials both as a powder for reconstitution and as a liquid solution (25 mg/mL) under the brand name Keytruda. The typical regimen is 2 mg/kg as an intravenous infusion every 3 weeks. side effects are common and can be severe. As many as half of treated patients develop immune related side effects as a result of immune enhancement including enterocolitis, dermatitis, endocrinopathy, pneumonitis, neuropathy, nephritis and hepatitis. Most of these reactions respond to immunosuppressive therapy, but some have resulted in fatalities and some have required long term therapy. Early recognition and prompt management of these side effects is an integral component of proper use of check point inhibitors such as pembrolizumab.