The mRNA vaccine against melanoma is not preventive, but a therapy tailored for high-risk patients. Associated with immunotherapy, it blocked relapses in 82.2% of cases after two years. The study explained by the doctors who recruited the patients for the phase III trial.
The melanoma it is a skin cancer often shrouded in fears and false beliefs. On the one hand there are those who underestimate the visible symptoms, delaying life-saving diagnoses; on the other, the recent news on the arrival of a “mRNA vaccine” and the results of the Phase III INTerpath-001 trial have generated dangerous misunderstandings online, confusing advanced therapies with miraculous prevention. To shed light on this pathology, starting from the risk factors up to immunotherapy and the most cutting-edge experimental treatments, we interviewed two experts from the IRCCS Foundation National Cancer Institute of Milan: Doctor Roberto PatuzzoDirector of the Complex Melanoma Surgery Unit, e Bianca TalioneMedical Director of the Complex Melanoma Surgery Unit.
Let’s start with the identikit of the disease: what exactly is melanoma?
Cutaneous melanoma is a malignant skin tumor that originates from melanocytesi.e. the cells located in the epidermis (the outermost layer of the skin) which have the task of producing the melanin to protect us from ultraviolet rays.
However, it must be remembered that these cells are also found in the eyes and in some mucous membranessuch as the oropharyngeal tract or the anal canal, where in fact forms of melanoma can arise, although much rarer in the Caucasian population.
How widespread is it in Italy?
As for the numbers, we are not talking about a rare disease at all: in Italy we record around 13,000 new diagnoses a year, with aincidence of 22 cases per 100,000 people.
Globally it is at fifth place among the most frequent tumors in both sexesbut there is a fact that should make us reflect: in population under 50therefore young and active, melanoma is the second most frequent tumor in males and the third in femaleseven becoming the first cancer found during pregnancy.
Besides sun exposure, what are the risk factors to keep in mind?
Risk always depends on a combination of environmental and genetic factors. Certainly theexposure to UV rays without protectionsevere sunburns and the use of tanning lamps are favorable factors.
At the level geneticthose who have a very light complexion (phototypes 1 and 2), a high number of moles or one familiarity with the disease has a greater risk.
So, in addition to external factors, does genetics matter as much?
Absolutely, it plays a huge role. Let’s think about theAustraliawhich has a record incidence of 42 cases per 100,000 people: this is not only due to the strong sun, but to the fact that the original population was made up of Northern European settlers who remained isolated from the rest of the world for over 300 years. This isolation amplified a genetic trait which, combined with the environment, enhanced the predisposition to melanoma. In general, the more aggressive forms of this pathology have a strong genetic derivation.
How can we notice a melanoma in time? Are there any visible signs?
Yes, and it is paradoxical that, despite being one of the few tumors visible to the naked eyemany patients tend to “put their heads in the sand”, delaying checks in the hope that the lesion will disappear on its own.
The most obvious symptom is the appearance of a new mole or the rapid transformation of an existing onealthough it should be noted that only the 40-50% of melanomas arise from pre-existing moles; the remainder 50-60% appears on previously perfectly healthy skin.
What do you need to pay attention to?
For self-observation we use the rule ofABCDE: you need to check Asymmetry, Edges (if irregular or jagged), Color (if not uniform), Diameter (if greater than 6 millimetres) and above all the Evolution over time.
There is also the “ugly duckling” rule: a lesion, perhaps even red and not necessarily dark, which grows quickly and appears visibly different from all the other moles on the body.
If a melanoma is removed promptly, 80% of patients recover permanently.
What is the clinical path from the operating room to subsequent therapies?
Once the doubtful nevus has been identified at the dermatoscopic clinic, worthy of histological assessment, a 3 mm excisional biopsy is performed for diagnostic purposes.
One key thing is that initial excision margins should not exceed 3-5 millimeters: it is useless and harmful to immediately make giant scars, because they would alter the lymphatic structure.
If the histological examination confirms the suspicion and the melanoma exceeds a certain thickness, we must perform lymphoscintigraphy and biopsy of the sentinel lymph node (it is the first lymph node where lymph drains from the primary tumor and is the point where tumor cells are most likely to arrive, ed.).
This allows us to understand if the tumor cells have started to travel in the lymphatic system and serves to stage the disease.
If the tumor is at risk of spreading, immunotherapy comes into play. How has it changed the rules of the game compared to the old chemo?
THE’immunotherapy represents the great epochal change in the history of oncology. Classic chemotherapy acted like a bomb: it killed rapidly replicating cells, affecting diseased and healthy.
Immunotherapy, however, is based on an opposite paradigm: reactivate and strengthen the patient’s immune system. Melanoma, like other tumors, uses specific mechanisms to evade our defenses and make itself “invisible”.
Immunotherapy drugs unlock this lock, removing the inhibitory brakes on our body and allowing lymphocytes to attack the disease. It is a revolution that allows us to chronicle the pathology: today, 50% of patients with advanced and metastatic disease manage to keep it under control for years.
There has been a lot of hype recently around the “mRNA vaccine” for melanoma. What exactly is it and who is it aimed at?
First of all, a dangerous misunderstanding must be clarified: it is not a preventive vaccine for healthy people. You don’t get the shot to avoid getting cancer. Let’s talk about a therapeutic vaccine And highly personalizedintended for patients who have already been operated on and have had a melanoma removed high risk of recurrence.
The mechanism is fascinating: we take a sample of the patient’s surgical tumor, send it to the laboratory and analyze its DNA. From there, we can identify up to 34 “neoantigens”i.e. abnormal proteins specific and unique to that individual patient.
With this information, we build a tailor-made mRNA. To use a metaphor: the vaccine provides the immune system with the “mug shot” exact number of tumor cells to look for. If we then combine it with immunotherapy, which in the meantime has “unlocked” the defenses and provided the weapons, we create a very powerful synergy to eliminate residual malignant cells.
Your institution participated in a huge clinical study on this combination (INTerpath-001 study). What results did you get?
The international study involved over 1,100 patients. As a Cancer Institute we are proud to have been the first center in the world in terms of number of enrollments, with well 182 patients followed. The results two years later are remarkable.
In the group of patients who received both the vaccine and immunotherapy, the82.2% he was free from recurrence (compared to 70% of those who only underwent immunotherapy). Furthermore, 88.5% were free from distant metastasesa (versus 80.2% of the control group).
From a practical point of view, how is administration carried out for the patient? Are there any serious side effects?
No, the safety profile is excellent. We have not recorded any increase in toxicity compared to the use of immunotherapy alone. The vaccine gives him classic effects of a vaccination: some fatigue, fever or pain at the injection site.
The protocol provides 9 intramuscular injections of the vaccine (one approximately every 26 days), combined with intravenous immunotherapy, for a total treatment duration of approximately one year.
What are the current limits of this treatment?
Today the challenges are natural logistics and economical: the vaccine is physically processed in the United States, with production times and costs that will need to be made more sustainable in the future, possibly freeing it in Europe.
Looking to the future, what are the next challenges for oncology?
However, the scientific perspectives are broad: we aim to apply these vaccines also to other cancers with no cure (such as that of the pancreas or lung), and we are investing in surgical de-escalation (interventions that are increasingly less destructive) and in liquid biopsyto find diseased cells with a simple blood test.
The objective of today’s oncology medicine is to chronicle the pathology and transform patients into long-term survivors, overcoming the rhetoric of the “battle won against cancer”.
However, before we can see this mRNA vaccine approved and available as standard therapy in our hospitals it will still take a long time: further trials will in fact be necessary, i definitive 5-year survival data (Overall Survival) and overcoming the long and indispensable bureaucratic approval processes by regulatory bodies, such as the EMA in Europe and the AIFA in Italy.
