Melanoma + immunotherapy Flashcards
What are the symptoms of melanoma?
-ABCDE
-Bleeding
-Itching
How common is mucosal melanoma?
5%
Eg. ocular, resp, GI, GU, gynae tracts
How is melanoma staged?
TNM
-Microscopically we comment on the presence/absence of ulceration (b/a) + mitotic rate (mitoses/mm3)
-Ulcerated + higher mitotic rate – more aggressive
-T Stage
-Breslow Thickness
T1 < 1mm
T2 1-2mm
T3 2-4mm
T4 >4mm
N Stage
M – Lung/Liver/Nodal/Brain/Bone
LDH use to add to staging – if elevated in metastatic disease – more aggressive
Why is ulceration of melanoma lesions significant?
It signifies that the disease is more aggressive
What is the prognosis of different stages of melaonoma?
-Stage IA 94% 5yr survival
-Stage IIB 5 and 10 year melanoma-specific survival probabilities with routine surveillance are 87% and 82%,
-Stage IIC 5 and 10 year melanoma-specific survival probabilities with routine surveillance are 82% and 75%,
-Stage IIIA 5 and 10 year melanoma-specific survival probabilities with routine surveillance are 93% and 88%,
-Stage IIIB 5 and 10 year figures are 83% and 77%, respectively
-Stage IIIC 5 and 10 year figures are 69% and 60%, respectively
- Stage IIID 5 and 10 year figures are 32% and 24%, respectively
Why is a BRAF mutation in melanoma significant?
It a mutation that can be targeted with meds. It gives more treatment options and therefore better prognosis
- 45% of skin melanomas
- Not seen on mucosal melanoma
- Its not inherited – just a mutation within the melanoma which if present drives the melanoma
What is BRAF wild-type?
No BRAF mutation
What is the MEK mutation?
In people with BRAF mutations, MEK mutations occur as a form of resistance
So melanoma with BRAF mutations is treated with medications specific to BRAF mutations and MEK mutation so it can be more effective for longer
What are Coley’s toxins?
It was the early form of immunotherapy where strep pyogenes was injected into the lesions and it worked to get the immune system to fight off the cancer
Lots of patients died of sepsis though
How is IL2 used to treat melanoma?
It’s manufactured as aldesleukin
- Used to boost the immune system to fight off the cancer
What are the treatments available for BRAF-wild type melanoma?
Immunotherapy only
How was chemotherapy discovered?
In WW2 they noticed that people that had died after mustard gas exposure had smaller lymph nodes and supressed bone marrow, so they created a liquid form of mustard gas to treat cancer and it worked
What are the 2 mutations that occur on T cells that prevent them from stimulating the immune system to fight the cancer cells?
CTLA-4 and PD-1
By blocking these, the T-cells aren’t inhibited and can fight off the cancer
Name some immunotherapy drugs used to treat melaonoma?
- Anti CTLA-4
Ipilimumab – Melanoma/Renal - Anti PD-1
Nivolumab – Melanoma/NSCLC/
Urothelial/NHL/H+N
Pembrolizumab - Melanoma/NSCLC/
Urothelial/NHL/H+N/Colorectal
Cemiplimab – Squamous cell cancer - Anti PD-L1
Atezolizumab – Breast/Urothelial/Lung
Avelumab - Merkel
Durvalumab - NSCLC - Adjuvant/Neo-adjuvant use
What is the current best treatment for metastatic melanoma?
Pembrolizumab + Nivolumab
Given for a year but studies showed that there was a response in people even if they couldn’t complete the year
What are some immunotherapy associated toxicities?
an -itis of any organ because the immune system is overstimulates and causes autoimmune disease that’s treated with steroids
It’s a contraindication for further treatment
Why was the checkmate 238 study significant?
It showed that the Nivolumab and Ipilimumab combination was most effective immunotherapy at treating BRAF wild-type metastatic melanoma
What was the keynote 054 study know for?
It showed that Pembrolizumab improved recurrence-free survival of stage 3 high risk melanoma
What was the combi-ad study famous for?
It showed that the combination of dabrafenib (D) and trametinib (T) is a successful adjuvant therapy for stage III BRAF-mutant melanoma
