Loading
Ten years after starting treatment, about half of patients with advanced melanoma treated with nivolumab plus ipilimumab were still alive, most without any further treatment, showing that immunotherapy can cure a disease that once killed most patients within a year.
Final ten-year analysis of the double-blind phase 3 trial of 945 patients with untreated advanced melanoma randomised to nivolumab plus ipilimumab, nivolumab alone, or ipilimumab alone.
Median overall survival was 71.9 months with the combination, 36.9 months with nivolumab and 19.9 months with ipilimumab; 10-year OS was 43%, 37% and 19%. Median melanoma-specific survival was not reached for the combination, with 10-year melanoma-specific survival of 52%. The survival curves plateaued after about three years, and most surviving patients had been off treatment for years. It is the longest follow-up of any checkpoint inhibitor trial and the definitive evidence that immunotherapy can be curative.
For patients with advanced melanoma, immunotherapy offers a realistic chance of long-term survival and probably cure, and the ten-year data show that patients who are alive and progression-free at three years rarely die of melanoma afterwards. Nivolumab plus ipilimumab gives the best long-term results but at a high price in serious side effects; nivolumab alone or nivolumab plus relatlimab are alternatives for patients at lower risk or with autoimmune concerns. The trial is also a caution about surrogate endpoints: the survival plateau took years to become visible.
Checkpoint inhibitors are now given to hundreds of thousands of patients a year, many in community clinics and emergency departments, so a common, explicit playbook for their autoimmune side effects saves lives. The guideline standardised when to stop, when to give steroids and when to escalate, and made multidisciplinary toxicity teams routine. It does not remove the judgement needed for rare events or for patients whose cancer is responding.
This paper launched the immunotherapy era. It was the first randomised evidence that taking a brake off the immune system could extend life in a solid cancer, and it introduced clinicians to immune-related adverse events and to responses that arrive late or after apparent progression. Ipilimumab alone has since been superseded by PD-1 antibodies and combinations, but every checkpoint programme traces back to this result.
Shares RELATIVITY-047, Relatlimab + nivolumab, CheckMate 067, LAG-3.
Shares ASCO 2021 guideline: how to recognise and manage the immune-related side effects of checkpoint inhibitors, CheckMate 067, CTLA-4, Advanced melanoma (unresectable stage III and stage IV).
Shares RELATIVITY-047, Relatlimab + nivolumab, LAG-3, Advanced melanoma (unresectable stage III and stage IV).
Shares Relatlimab + nivolumab, CheckMate 067, LAG-3, CTLA-4.
Shares John Haanen, Immune-related adverse events (irAEs), CTLA-4, Ipilimumab.
Shares John Haanen, Hodi 2010: ipilimumab, the first checkpoint inhibitor, extends survival in metastatic melanoma, CheckMate 067, Immune-related adverse events (irAEs).
Shares F. Stephen Hodi, Hodi 2010: ipilimumab, the first checkpoint inhibitor, extends survival in metastatic melanoma, Immune-related adverse events (irAEs), No one can predict who responds to immunotherapy.
Shares Relatlimab + nivolumab, Advanced melanoma (unresectable stage III and stage IV), Bristol Myers Squibb, Nivolumab.