Uveal Melanoma at ASCO 2019

What Is Available for the Treatment of Uveal/Mucosal Melanoma?

Presented Sunday, June 2, 2019

https://meetinglibrary.asco.org/record/167893/video

Circulating tumour DNA to predict survival on Dab and Dab/Tram

Work from the Polsky Laboratory


https://meetinglibrary.asco.org/record/174180/abstract

• circulating tumour DNA- easier to access, represents ALL the tumour burden, not just like a single lesion with a biopsy
• detects BRAF mutation in the blood

Important questions:

- does ctDNA have a prognostic value? yes
- can one measure response to treatment by ctDNA? yes
- can one anticipate upcoming resistance to targeted therapy? they didn't check that



patients from the Combi-D study 

1st large-scale ctDNA analysis

technique: droplet digital PCR
very sensitive but only 'as good as you know what to look for'


detectable ctDNA at begin of treatment = poorer prognosis

elevated ctDNA at baseline was associated with survival as a continuous variable, not as categorical (yes/no) variable

higher ctDNA at baseline = worse outcome


INTERESTING
achieving negative ctDNA at 4 weeks was extended with PFS and OS, especially in patients with elevated LDH





More on ddPCR
https://en.wikipedia.org/wiki/Digital_polymerase_chain_reaction

IL6 and CRP- abstract 100

Session 'Fine-tuning response to immune therapy'

Serum IL-6 and CRP as prognostic factors in melanoma patients receiving single agent and  combination checkpoint inhibition.

Jeff Weber 

https://meetinglibrary.asco.org/record/174917/abstract


CRP is produced in the liver and higher levels are associated with poorer outcome in Melanoma. IL6 is a cytokine with both and pro- and anti-inflammatory properties, induces CRP production in the liver.


Both were measured before and on treatment with immuno (Ipi, Nivo)

Low IL6 patients did well
High IL6 patients did less well

Checkmate 066- Nivo vs DTIC
same here- but also on DTIC so it's a prognostic marker and not specific to immune therapy: high IL6 poorer outcome


CRP- similar: patients with higher CRP level have shorter survival


How does it work?

CRP suppresses T-cell and dendritic-cell function and suppresses antigen-specific T-cell generation

it is interfering with the contact between the T-cell and the antigen-presenting cell = disrupts communication 


Trial coming IL6- blocking antibody, combined with immune therapy

From discussion

IL6 biology- it has a double-function, so the outcome is context-dependent