Ara Darzi: The promise of immunotherapy

I am proud to be a cancer surgeon: surgery accounts for half of all long-term cures in cancer and provides the cornerstone for the treatment of most solid cancers. 

But even I recognise that the most progress in tackling cancer in recent years has been in the development of new anti-cancer medicines that harness the immune system.

Advances in immunotherapy in the past decade have been spectacular. There are now 13 products licensed for use in Europe which are transforming the lives of patients with advanced cancer. Over 2000 trials of immunotherapeutic agents are underway, including several to treat covid. Research is revealing scores of new agents with action against conditions including rheumatoid arthritis, multiple sclerosis, Alzheimer’s disease, and infectious diseases.

However, there is a major barrier to further progress. The research needed to develop these treatments is costly, and a complex infrastructure is necessary to deliver them. There are just 10 centres in the UK able to administer cell therapies that involve taking the patient’s own cells, altering them, and returning them, and 200 in the US. 

There is currently great excitement around CAR (chimeric antigen receptor) T-cell therapy. It has been effective in treating some blood cancers and is undergoing trials for many other cancers. 

Gene therapy, another promising type of immunotherapy, involves correcting a faulty gene or introducing a new one to fight disease. Even though we have new drugs that are more effective than in the past, they target just 5% of the 500 cancer genes we know of. 

If we are to realise the immense promise of these agents, we have to confront this challenge. Governments, regulators, biotech companies, and institutions must come together so that we can harness innovations that could benefit millions of patients worldwide, as set out in a new report by a panel of international experts presented at the Qatar Foundation’s World Innovation Summit for Health (WISH) this month [15-19 Nov], which I chair.

One of the most famous recipients of immunotherapy is former US president Jimmy Carter, who was diagnosed as having metastatic melanoma in 2015 which had spread to his brain. The typical survival period for patients with this type of cancer is less than a year. Yet Carter is still alive, aged 96, and cancer-free.

Among the first patients to be treated in the UK were 53 year old Graham Threader and 18 year old Mahmoud Kayiizi in an experimental trial at University College Hospital, led by Martin Pule. Their tragic story was told in a BBC documentary, War in the Blood, broadcast in 2019. Both patients were terminally ill and had run out of options, but the experimental therapy failed and they died.

The knowledge gained from their cases was critical to the recovery of five other patients shown in the programme, however, who were successfully treated this way. 

An urgent need remains to develop more effective treatments, capable of improving survival and quality of life. Often multiple companies carry out trials on the same technology but with different measures of success, making it difficult to combine results and slowing down the validation of a treatment. Then there is cost. Novel immunotherapies can range from $100,000 to more than $1m per patient, including hospital costs for their administration. Yet patients who have run out of options should have access to effective therapies. 

The WISH report recommends new approaches to support research, the establishment of centres of excellence, and support for collaborative trials such as platform trials which test different compounds in parallel, using the same protocol and control arm, reducing the number of patients required, increasing flexibility and saving costs. 

It also calls for experiments with novel pricing mechanisms, such as payments dependent on the length of response (the epilepsy treatment Retigabine [ezogabine] in France), pricing linked to reduction in hospitalisation (the combination heart failure treatment Entresto [sacubitril/valsartan] in the US), and agreement to cover costs in excess of an annual cap (the macular degeneration treatment Lucentis [ranibizumab] in Germany).

Immunotherapies are revolutionary treatments. But we must act now to ensure they are available to patients who can benefit from them. We need a national strategy to identify the need, develop standards, and focus resources where they will make the largest difference to our patients.

Ara Darzi is a surgeon and Co-Director of the Institute of Global Health Innovation, Imperial College London. 

Competing interests: None declared