Dermatology Made Easy is based on the most popular topics from DermNet NZ's vast array of material. The book combines the essential focus of the ‘Made Easy’ book series with the authority and knowledge base of DermNet NZ's unparalleled resources.
Author:Anoma Ranaweera B.V. Sc; PhD (Clinical Biochemistry, University of Liverpool, UK); Chief Editor: Dr Amanda Oakley, Dermatologist, Hamilton, New Zealand, December 2014.
Pembrolizumab (trade name Keytruda®, formerly known as lambrolizumab) is a drug marketed by Merck and Co (New Jersey, USA) that targets the programmed death 1 (PD-1) receptor. The drug is intended for use in treating metastatic melanoma.
On September 4, 2014 the US Food and Drug Administration (FDA) approved pembrolizumab as a breakthrough therapy for the treatment of metastatic melanoma. It was approved for use in New Zealand in September 2015, and funded by PHARMAC for some patients with unresectable or metastatic melanoma from September 2016.
Pembrolizumab is indicated for the treatment of patients with unresectable or metastatic melanoma and disease progression following treatment with ipilimumab. For melanoma patients whose tumours express a gene mutation called BRAFV600, pembrolizumab is intended for use after treatment with ipilimumab and a BRAF inhibitor (eg vemurafenib or dabrafenib), a therapy that blocks activity of BRAF gene mutations.
Combination therapy is under investigation and may improve response rates. Pembrolizumab is under investigation in other malignancies. It has been reported to have some effect in metastatic merkel cell carcinoma.
The programmed death receptor 1 (PD-1) is a surface molecule expressed on antigen-stimulated T-cells as well as monocytes, B-cells, and dendritic cells. In normal cells the PD-1 receptor acts as an immune checkpoint receptor enabling self-tolerance by T-cells, thus preventing autoimmune reactions.
When unbound, PD-1 allows the normal response by T-cells to proceed.
However, binding of PD-1 to its ligands, PD-L1 (programmed death receptor ligand 1) and PD-L2, suppresses the immune response by inducing downstream signalling that inhibits the proliferation of T-cells, cytokine release and cytotoxicity.
No formal pharmacokinetic drug interaction studies have been conducted with pembrolizumab.
In clinical trials, the most common side effects (greater than or equal to 20%) in patients receiving pembrolizumab 2 mg/kg every 3 weeks were:
The most frequent (greater than or equal to 2%) serious adverse drug reactions observed with pembrolizumab were renal failure, dyspnoea, pneumonia, and cellulitis.
Pembrolizumab also has the potential for severe immune-mediated adverse effects. In the 411 clinical trial participants with advanced melanoma, severe immune-mediated adverse effects included pneumonitis, colitis, hypophysitis, hyperthyroidism, hypothyroidism, nephritis, and hepatitis.
One report has described skin problems arising in 42% of 83 patients on pembrolizumab. Development of skin problems was associated with longer progression-free intervals.
Darkening of hair has been reported in a few patients taking PD-1 inhibitors for non-small cell lung cancer .
Freites-Martinez A, Kwong BY, Rieger KE, Coit DG, Colevas AD, Lacouture ME. Eruptive Keratoacanthomas Associated With Pembrolizumab Therapy. JAMA Dermatol. 2017 Jul 1;153(7):694-697. doi: 10.1001/jamadermatol.2017.0989. PubMed PMID: 28467522; PubMed Central PMCID: PMC5523926.
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