Immunotherapy Flashcards
What are the investigations for reoccurrence and metastases?
- US and FNA (US variable depending on type of cancer e.g. bronchoscopy)
- CT
- PET-CT
- MRI brain
- U+Es, LFTs
What immune side effects can immunotherapy cause?
They can cause immune-mediated toxicities due to activation of the immune system to target cancer cells. These can include worsening of autoimmune conditions as well as itchy skin rashes, diarrhoea, endocrinopathy, pneumonitis, nephritis, hepatitis, uveitis, paraesthesia and neuropathy. The mainstay of toxicity management is immunosuppression with corticosteroids,
Why is diarrhoea caused by immunotherapy treated differently from that caused by chemotherapy?
- Chemotherapy side effects are from damage to rapidly dividing cells. In the GI tract this can result in malabsorption of fluid and increased secretions. Usually a break from chemotherapy and loperamide is sufficient to control it. Patients my require admission for hydration and management of electrolyte disturbances.
- Immunotherapy drugs > diarrhoea due to inflammatory colitis (due to cell damage) and can progress without immunosuppression. With severe colitis patients are at risk of perforation and peritonitis. If not responding to steroids they may require more specialist immunosuppression e.g. infliximab, though needs oncologist supervision.
What are BRAF inhibitors?
- A type of targeted therapy that only works in patients who have a specific genetic mutation in their cancer.
- Only ~50% of patients with melanoma do
- For patients with BRAF V600 mutation, treatment with either BRAF inhibitors or immunotherapy are options
What provides some cancers with better clinical outcomes?
Presence of immune cells (such as T cells) correlates with better clinical outcomes: earlier stage, absence of metastases, decreased relapse rates, better survival.
What types of cancers are increased with suppression of immune system?
- HIV»_space; haematological
- Transplant patients - all
What examples are there of checkpoint inhibitors?
- Pembrolizumab
- Nivolumab
- Ipilimumab (can be used in conjunction with Nivolumab)
What does FDG avid mean?
When tumour cells take up glucose (or FDG) - term used when interpreting a PET scan.
What are the side effects of immunotherapy?
- Any monoclonal may be associated with an Infusion Related Reaction (IRR) - typically anaphylactoid in nature and are treated similarly although adrenaline is reserved later in the treatment pathway
- The CPi’s may cause immune activation against normal tissues (-itis) - treat with steroids
What are examples and the side effects of tyrosine kinase inhibitors?
e. g. imatinib, ibrutinib
- Diarrhoea
- Rash
- LFT abnormalities
- Cytopenias possible in haematological causes
- Most of these can be treated by holding the drug and reintroducing it at a lower dose
What are examples of BRAF inhibitors?
Dabrafenib - targets mutated BRAF protein in MAPK pathway and blocks it (orally). Can be used in conjunction with trametinib which targets another protein in the same molecular pathway. The 2 drugs in combination can have a rapid effect on melanoma but this is often short-lived and they may require another treatment after several months.
What is the treatment pathway for melanoma?
Most patients with cutaneous malignant melanoma will be cured by surgery alone. High risk patients (stage 3 or 4 completely resected) are offered systemic adjuvant treatment with curative intent (in breast it is surgery then radiotherapy). Adjuvant treatment with either immunotherapy (nivolumab or pembrolizumab) or targeted therapy (dabrafenib and trametinib) is given for 1yr and it significantly reduces the risk of reoccurrence.
How does NICE review all new treatments?
Reviews them as they are licensed and decided whether the NHS can fund them. They use the term QALY (Quality Adjusted Life Year) to judge the cost-benefit ratio of a new treatment. Exceptions may be made for more expensive drugs in diseases that have limited treatment options and for drugs used towards the end of life. The Cancer Drugs Fund was introduced as an interim measure for new drugs in England but has now been incorporated into NICE.
