Metastatic melanoma, new immunotherapy mix releases ‘brake’ on treatments

In patients with metastatic melanoma never treated before, the combination of relatlimab, anti-Lag-3 antibody, and nivolumab, anti-Pd-1 antibody, reduced the risk of disease progression by 25%. Median progression-free survival reached 10.12 months with the combination of the two immunotherapy drugs, compared with 4.63 months with nivolumab monotherapy. These are the results of the phase III study Relativity-047, presented at the 2021 Congress of the Asco (American Society of Clinical Oncology), ongoing until tomorrow in virtual form. Lag-3 is an immune checkpoint, a ‘brake’ used by the tumor to circumvent the response to immuno-oncological therapies, which joins checkpoints already known as Pd-1 and Ctla-4, explains Bristol Myers Squibb (Bms) in a Note. “The first studies on relatlimab were started about 4 years ago at the ‘Pascale’ in Naples – recalls Paolo Ascierto, director of the melanoma oncology unit, oncological immunotherapy and innovative therapies of the Campania Institute – in which we demonstrated how to unlock the new brake on the system The challenge now is to understand which patients are candidates for this treatment and Lag-3 can be a valid biomarker for selecting the best therapy “. “In the international study, 714 patients with metastatic or inoperable melanoma were involved” and “the significant clinical benefit offered by the new relatlimab and nivolumab combination in the first line, with good tolerability, is evident”, highlights Ascierto. “Immune checkpoint inhibitors in monotherapy or in combination have changed the history of the disease and improved survival rates – underlines the expert – Nonetheless, there remains a percentage of patients who could benefit from the new combination therapy that influences complementary cellular pathways. to enhance anti-tumor activity. Therefore, targeting the Lag-3 pathway in combination with Pd-1 inhibition may prove to be a key strategy to enhance the immune response. ” At Asco also new data on nivolumab-ipilimumab, 49% treated are alive at 6 and a half years.At the Asco meeting – reports Bms – the results of the international phase III study CheckMate-067 were also presented, on the combination of two immuno-oncology molecules nivolumab and ipilimumab at the forefront of advanced melanoma. “945 people were enrolled – reports Ascierto – 49% of patients treated with the combination are alive at 6 and a half years. In particular, the median overall survival was 72.1 months with nivolumab plus ipilimumab (the longest so far reported in a phase III study in advanced melanoma), compared to 36.9 months with nivolumab and 19.9 with ipilimumab. The impact of the combination on overall survival is therefore decisive, especially considering that, prior to immunotherapy , the life expectancy of patients with metastatic melanoma was approximately 6 months and less than 10% were alive at five years “. “Another important aspect – remarked the oncologist – is represented by the fact that 77% of patients alive at 5 years and who received the combination no longer needed to receive systemic treatment. The dual immunotherapy therefore shows a significant ” memory effect ‘: its effectiveness is maintained in the long term, even after the end of treatment “.

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