Bioderma Congress Reports EADO 2024

Speaker: Prof. Caroline Robert (Paris, France)

Reports written by Dr. Oriol Yélamos

We have different types of biomarkers: prognostic biomarkers, predictive biomarkers (they predict treatment response), and both prognostic and predictive biomarkers.
What you want on a biomarker is very high sensitivity and specificity with an area under the curve close to 1.
Staging (CT scans, LDH values, BRAF status, comorbidities...) is per se a way to stratify our patients.
We are going to take a look at different biomarkers.

LDH: an old biomarker

Patients with high LDH still benefit from new therapies (immunotherapy, targeted therapies), but they have a worse outcome compared with patients with normal LDH. Why is that? We believe that high LDH means high tumor burden, but also it is related with the tumor microenvironment, metabolism and a more acid environment, which negatively impacts on oncogenic pathways.
There are 5 different isoforms of LDH, which have critical roles in metabolism. What happens is that when we ask for LDH determination on a routine blood test we are not really measuring LDH but a reaction led by the LDH enzyme. So, Dr Robert's group studied the different isoforms of LDH and showed that LDH1 is good, LDH4 is bad. They have shown then that is good to look not only if LDH is high or normal, but to assess the LDH1/LDH4 ratio.

PDL1

Expressed in tumor cells and induced by IFN-gamma. The problem is that PDL1 is not homogenously expressed in the tumor and also can be expressed by cells around the tumor.
Intuitively, treatment response would be better if PDL1 expression is high, but there's not clear statistical association, although there's a trend.
There's a new test: PD1/PDL1 proximity ligation assay, which seems a promising test to predict treatment response. However, it's still not widely available and very expensive.
 

TMB (tumor mutation burden)

The rationale is the following: More mutations, more neoantigens and therefore better treatment response. The problem is that although there's a trend towards more response in high-TMB tumors, not all studies show this. Hence, the importance is not the number of mutations, but how many clonal mutations are found.

Multi-omics classifiers for immune checkpoint inhibitors (ICI) in melanoma, transcriptomic signatures

The combination of multiple molecular techniques is the future but can't be used routinely now because of high cost.

Liquid biopsy

Multiple studies analyze circulating tumor DNA (ctDNA). ctDNA is rarely found on the blood of early melanomas but is commonly found (90%) is advanced melanoma, and this is why it can be potentially used to detect aggressive melanomas. The problems are related to the detection technique, since nowadays we don’t know the threshold of ctDNA that is clinically relevant. Hence, liquid biopsy nowadays is only done for research purposes since there are no standard methods. However, this is definitely one of the most promising techniques.

T-cell traficking cells

There are some endothelial cells that may be a good treatment biomarker for ICI.

Gut microbiome

AntiPD1 response is also associated with some gut germs. There will be a whole session on this topic.

Clinical early response

Patients who respond early to ICI they do very well. So this can be a very good marker.

Speaker: Dr. Aimilios Lallas (Greece)

Report written by Dr. Oriol Yélamos

The history of Spitzoid tumors has been peculiar since their initial diagnosis in the 1940's by Dr Sophie Spitz. Initially they were described as childhood melanomas but only 9% died when at that time 90% of adult melanoma patients died. Now we know that most of these lesions are simply peculiar nevi called Spitz nevi (SN). We also know that 80% of spitz nevi (SN) disappear over time.

SN have typically 3 dermoscopic patterns: starburst pattern, dotted vessels, negative network. Also, typically they are symmetrical. However, SN can be asymmetrical and can have melanoma-specific structures. To make it more complicated, some spitzoid melanomas look perfectly normal and symmetrical. Also, some lesions when excised cannot be easily diagnosed as benign or malignant and are called atypical spitz tumors (AST). Luckily, 99% of AST survive.

Therefore, what is crucial is age; if less than 12 years typically these lesions are SN, whereas 13% of spitzoid lesions over the age of 12 are melanomas. So what we do is, spitzoid lesion after 12 we excise them. Before 12, we could follow (or do nothing) lesions that are symmetrical and have a starburst pattern.

Speaker: Prof. Axel Hauschild (Kiel, Germany)

Report written by Dr. Oriol Yélamos

The incidence of NMSC is increasing, and obviously also advanced NMSC. Importantly, NMSC is not only SCC and BCC, but it also includes sarcomas, among others.

Advanced SCC

Before newer treatmens such as immunotherapy, survival was less than 3 years in advanced SCC. Fortunately, now we have effective treatments such as cemiplimab and pembrolizumab, with response rates around 30-50% in advanced tumors.
Also, now we have data in the neoadjuvant setting, showing promising results especially if complete pathological response is achieved. So maybe in these patients with advanced SCC we may not need to do further adjuvant immunotherapy (similarly to what has been shown in melanoma).
So, we need data and biomarkers to know which patients may benefit from adjuvant treatment after neoadjuvant treatment (this approach is called perioperative treatment -> neoadjuvant + surgery + adjuvant). The issue is that for the moment is that we have limited data and these treatment regimens are not approved.
There's also some data with combined treatment with ipilumab + nivolumab vs nivolumab in a very short course before surgery. Another study combined avelumab with cemiplimab prior to surgery. We have to accrue more data to draw conclusions.
Intralesional treatments are also used in both SCC and BCC: intralesional cemiplimab, intralesional daromun, intralesional RP1... Data is still preliminary but promising.

Advanced BCC

Now we are using the new EADO classification for advanced BCC (Peris K et al. Eur J Cancer 2019).
The two classic treatments are vismodegib and sonidegib, but in second line we have cemiplimab, which is used in case of progression to sonic hedgehog inhibitors (SHI) or in cases of intolerance or contraindication to SHI.
There's a pilot study using sonidegib plus cemiplimab which seems promising but no data is available yet.

Angiosarcoma

In very advanced angiosarcomas an option could be to use ipilumab + nivolumab. Why could we use it? Since there's a study using this combination in Kaposi sarcoma with 78% response rate.

Merkel cell carcinoma (MCC)

Avelumab is the only drug approved in MCC with 40% response rate (not that great but better than what we had). So there's room for improved treatment and also for treatment combination.