These are, in summary, the results that emerged from a final phase 3 INTerpath-001 study presented in a plenary session at the Congress of the European Society of Medical Oncology (Esmo) and which will soon be published in the New England Journal of Medicine but which has also been widely referenced in the prestigious scientific journal "Nature".
The study on the new adjuvant therapy, i.e. one that can be used post-operation, involved 1,137 patients with high-risk melanoma in 157 centers around the world, with Italy in first place in terms of the number of patients enrolled. The addition of the vaccine to the "pembrolizumab" immunotherapy, as mentioned, at two years reduced the risk of recurrence by 42% and the risk of distant metastases by 38% compared to what can happen using immunotherapy alone. In Italy, the eligible patients would be 5 thousand per year, out of 13 thousand new annual cases of melanoma.
According to experts, what has emerged represents a highly anticipated result, as well as based on a decidedly cutting-edge technique. In fact, the vaccine (mRna-4157) was produced in a personal way, "tailor-made" for the individual patient. In essence, created in a totally specific manner for the unique mutations of the individual patient's tumor. According to what is specified, it is produced by sequencing the DNA of the tumor removed by the patient himself.
But how does this particular and innovative vaccine work in detail? mRNA - messenger ribonucleic acid, i.e. a molecule that carries genetic information from DNA, acting as a sort of "instruction manual" - is essentially synthesized in the laboratory. The final objective is to transport the genetic instructions to produce up to 34 neoantigens, i.e. mutated proteins unique and exclusive to the tumor cells of that specific individual.
9 administrations are needed, for a year. The vaccine, the experts reported, has among other things the power not only to stimulate immune cells against melanoma, but also allows, even after the end of the treatment, to develop an immunological memory capable of recognizing and targeting any residual tumor cells over time.
So, once the mRNA vaccine is injected, what happens? Experts point out that the patient's cells produce these neoantigens, highlighting to the immune system a sort of "mug shot" of the target to be fought and eliminated, i.e. the tumor cells still circulating. This mechanism actually works by preventing relapses.
According to the opinion of Dr. Michele Del Vecchio, head of Melanoma Medical Oncology at the National Cancer Institute of Milan, a center that involved the largest number of patients in the world in the study (82), INTerpath-001 represents "the first and only phase 3 study that has demonstrated that, thanks to the combination of the mRNA vaccine with immunotherapy, it is possible to obtain superior results to standard therapy. Furthermore, the new combination has shown good tolerability, without an increase in side effects".
For Paola Queirolo, coordinator of the Melanoma, Skin Tumors and Immunotherapy Network of the Genoa Metropolitan Hospital, the one developed is "a non-preventive vaccine for healthy subjects, but a therapeutic one after surgery, designed starting from the molecular characteristics of each patient's tumor. Its aim, she added, "is to further strengthen the immune system against the tumor".
In the opinion of Paolo Ascierto, president of the Melanoma Foundation, with this vaccine "we no longer administer a generic cure, but we reprogram the immune system to destroy the cancer in the unique imprint of each individual patient".
At the moment, it should be underlined, the vaccine against melanoma is not yet available. Approval from the regulatory bodies will be required but in the meantime the possibility of activating specific access programs for the patients involved will be evaluated. The vaccine, it has finally emerged, could allow, based on the same mechanism, to broaden the spectrum, so much so that there are already active studies for mRNA vaccines for other tumors as well. However, there is a critical issue, that of high costs. An important challenge, in this sense, will be to work to reduce the price to guarantee access and sustainability for healthcare systems.
