Melanoma Flashcards
What is CTLA-4
A regulatory protein. Sits on surface of T cells- when binds to B7, dampens activation of that T cell when being stimulated and costimulated by dendritic cells.
Ab against CTLA-4 is ipilimumab which turns off this dampening of the immune response
What is PD-1
PD-1 is an immune protein on the surface of effector T cells. When it binds to PD-L1 on the cancer tissue cells, shuts down the T cell hence limiting autoreactivity against cancer cells. Anti PD1 antibody turns off this turning off effect in order to drive the immune response against the cancer.
Side effects of ipilimumab
Rash
Diarrhoea
Autoimmune hepatitis
Autoimmune thyroiditis
Severity determines how should be managed
Immune related adverse events: seldom life threatening if recognised. eg hypopit,thyroid, adrenal - should not need to give anti-immune therapies eg steroids
Life threatening skin rash or hepatitis or colitis- give high dose steroids and may need immunosuppressive agents.
There are treatment algorithms
name of anti-PD1
pembrolizumab
nivolumab
well tolerated
fewer immune side effects
CR rate 10% but overall clinical benfit (CR +PR + stabilistaion) is over 50%
What is meant by an immune check point.
T cell activity is regulated by various immune check points in order to limit collateral tissue damage during the immune response
What is dabrafenib and how does it work?
Melanoma new drug.
Targets MAP kinase pathway -BRAF inhibitor.
Oral agent.
What is vemurafenib and how does it work?
Melanoma new drug.
Targets MAP kinase pathway -BRAF inhibitor.
Oral agent.
45 percent of melanomas have the BRAF mutation which makes the MAPK pathway constitutively active
This promotes proliferation and prevents apoptosis
What is trametinib and how does it work?
MEK inhibitor of MAP kinase pathway
New melanoma drug
What is cobimetinib and how does it work?
MEK inhibitor of MAP kinase pathway
New melanoma drug
What are the side effects of vemurafenib?
rash arthralgias photosensitivity LFTs keratoacanthoma and SCCs
What are the side effect so Trametinib?
rash diarrhoea peripheral oedema asymptomatic reduction in LVEF blurred vision, central retinal occlusion, detachment
What are the side effects of dabrafenib?
DRUG FEVER alopecia skin arthralgias SCC, keratoacanthomas
Is it better to use BRAF and MEK inhibitors together or separately?
Together
Does it make a difference if PD-L1 expression or not
pembro yes increase response rate
nivol no
Umbrella vs basket study
basket all same mutation different cancers
umbrella all same cancer but different mutations
What types of UV?
UVA and UVB
most significant predictors of biological behaviour
depth
presence or absence of ulceration
acral lentiginous most common type in what people
asian
stain in melanoma
melaninA andS100
Stage4 and what things make A B or C
subcut or nodal mets A
lung and normal LDH B
not lung or high LDH C
staging
1- tumour under 1mm and no ulceration or 1-2mm and no ulceration or under 1mm and ulceration
2-deeper but no LN
3-LN
4-mets
stage 1 non need for imaging to look at rest of body
why take out LN in melanoma stage 3
no survival benefit
but palliative benefit as cause pain
if brain mets, what can you do
resect if single lesion
stereotactic if three under 3cm
multiple mets- whole brain
survival advantage
Who is BRAF mutated
tends to be those with intermittent sun exposure
KIT is if chronic sun exposure
if lots of acral exposure, tends to be NRAS and KIT
mucosal tends to be KIT
dabraf vs vemuraf
Vem is V600E mutation specific, does NOT get into CNS
Dabraf is not V600E specific, gets into CNS
need to give both with trametinib
APPROACH to metastatic melanoma
- is it resectable
- If not resectable what is the BRAF status? IF can, put on BRAF/MEK comb
- If no BRAF mutation then put on Anti PD1 agent
Fotemustine used when
rapidly advancing disease with cerebral mets
