July 2021: The US Food and Medication Administration (FDA) has expanded the indications for pembrolizumab (Keytruda), an immunotherapy drug, to encompass any cancer with a high mutational burden (TMB-H). The new authorisation is for adults and children with advanced TMB-H solid tumours that are continuing developing after prior treatment and for which no other therapeutic alternatives are available.
TMB (tumour mutational burden) is a measurement of the amount of gene mutations (changes) within cancer cells that can be evaluated using a lab test. Cells with a high number of gene mutations (a high TMB) are more likely to be identified as aberrant and attacked by the body’s immune system.
An immune checkpoint inhibitor, such as Keytruda, is a type of medication. It works by assisting the immune system in recognising and attacking cancer cells.
Keytruda has previously been licenced to treat a variety of malignancies, including lung, head and neck, stomach, liver, kidney, bladder, and skin cancers, as well as lymphoma in some cases.
Keytruda was originally approved for all advanced solid cancers with various gene alterations, including high levels of microsatellite instability (MSI-H) and mismatch repair deficiency (dMMR). MSI-H or dMMR cancer cells have problems repairing DNA damage. As a result, they may appear to be extremely different from regular cells, making them more noticeable to the immune system.
The latest FDA approval is based on a clinical experiment in which TMB was detected in patients’ tumours. TMB-H malignancies were found in 102 (13%) of the 790 patients screened. Small cell lung cancer, cervical cancer, endometrial cancer, anal cancer, and vulvar cancer were the most prevalent TMB-H malignancies in the study. During treatment with this medicine, 29 percent of the 102 patients with TMB-H tumours reacted (shrank or vanished). The average time to receive a response was 30 months, with half of the responses taking at least two years.
Keytruda was authorised for the new indication under the FDA’s expedited approval and priority review processes, which allow medications to be approved faster for critical conditions. After receiving fast approval, the drug’s manufacturer must submit further clinical data to establish the drug’s benefit. Priority review indicates that the FDA aims to make a decision within six months rather than the normal ten.
Keytruda is administered as an infusion into a vein every 3 to 6 weeks.
Fatigue, fever, cough, shortness of breath, nausea, itchy skin, rash, decreased appetite, constipation, muscular or joint pain, and diarrhoea are the most typical side effects of this medication. When the medicine leads the immune system to target normal cells in the body, less common but more dangerous adverse effects can develop. This can cause major complications in the lungs, colon, hormone-producing glands, liver, skin, and other organs.