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

The Melanoma Abstracts

As we make the last preparations for ASCO2019, a detailed look through the Abstracts gives a good idea of what is being studied in research and what are the "hot" areas for potential drug/therapy development and management. 

The searchable Abstract lists are here . 

I am hoping for some decent data on the anti PD1 PLUS combinations to prevent acquired resistance in the immunotherapies and also some strategies to improve the durability of Targeted Therapies. 
I also hope we have some better REAL WORLD data that will enrich what we have from the Clinical trials on optimal sequencing of therapies, identification and management of side effects and the most useful imaging and diagnostics to predict response and progression.  It is also also worth spending time learning from the other disease areas that use the same drug classes as us, to see what we can share from their experience.

Melanoma- the big issues

also- the MPNE conference hack ;-)

Before any conference we attend, 

• we make a list of the most relevant topic
• screen the program for any session related those topics
• make a time table (you've seen the one on the first post) and agree who attends which session in case they are in parallel 

Our relevant topics

- how do we overcome resistance in Melanoma?

- brain metastasis and leptomeningeal disease

- neo-adjuvant and adjuvant options- plus the long-term consequences for patients

- uveal and other rare Melanomas 

and then always

- upcoming developments

- the unexpected 

Ready, steady- packing!

Getting ready for a week of learning and meetings and always a moment to look back at what has happened since the first time I packed my suitcase for ASCO (wonder what I'll forget this time...).

My first ASCO was in 2011- and THANKFULLY, a lot has changed in Melanoma since. Only 15% of Stage 4 patients were still alive after 2 years- and Peter, my husband had just been diagnosed with the Stage 4 Melanoma. The then standard of care- DTIC- was something that should have never been called 'a standard', let alone 'care', calling it a 'measure of desperation' would have been more appropriate.

In a situation where patients only have desperate measures available, either because there is no efficient standard of care like DTIC in 2011 or they have exhausted all available lines of therapy, clinical research and in particular, clinical trials, are becoming particularly important.

However, also research follows a normal distribution- there is the good, the bad and the ugly. Trials tend to be designed to please anyone's interest BUT the patient's, despite the claims to the contrary (the Joker: BUT THE REGULATORS WANT IT!)- some more of my thoughts on the topic here No interest can take precendence. 

So understanding enough of the underlying Science AND being able to identify and choose clinical trials with a design that is good for patients suddenly becomes the best chance at beating the beast- and spending a week in an ice-cold and enormous conference centre with over 30 000 other people not knowing anyone really, a very good idea indeed.

This year, there will be 4 of us attending- which should allow us to blog but also post in different languages on various forums. We do speak quite a few languages among us but obviously, never enough, so thank you for following and sharing in your own language! 

As every year, we will do our best to cover the session content - straight from the session- and then tidy up and complete afterwards. We will also attempt to add further reading links, just like on the forum, so everyone can continue learning. Any questions, comments, things not clear- please comment on the blogs and we can answer!

It's time again!

We have started preparing for ASCO in Chicago!

ASCO is the world's largest oncology congress and one of the conferences where Melanoma updates are presented. 

As every year, we will cover the latest in #Melanoma news here on this blog- just getting started. 

Here is the first overview of sessions with interest for Melanoma patients from our shared team-up calendar: 

This year, less on Melanoma but a lot on immune therapies which are obviously equally relevant to us!