By Aisling McMahon, Alanna Kells and Sinéad Masterson

CAR-T therapies (Chimeric Antigen Receptor T-Cell Therapy) have demonstrated remarkable potential for the treatment of certain blood cancers. CAR-T therapy is a cellular immunotherapy which involves the extraction of a sample of a patient’s white blood cells (T-cells) which are then modified outside the body to increase their ability to target and eradicate cancer cells more effectively These modified cells are subsequently reinfused into the patient’s body. When the therapy is successful, it has in some cases led to remission of cancer for patients who were previously terminally ill with no alternative treatment options. There, are however, side effects to CAR-T therapies which can prove fatal, and must be carefully managed.

CAR-T Therapy in Europe

The first CAR-T therapies were approved for use in Europe in 2018. Currently, six main CAR-T therapies are approved for the treatment of blood cancers including certain types of leukaemia, lymphoma, and multiple myeloma. These therapies are approved for use for specific clinical indications – which differ depending on the CAR-T therapy –  and in certain circumstances e.g. where the disease has returned and existing treatment options such as chemotherapy have been tried and failed.  Recent studies have suggested that CAR-T therapies may offer promise in the treatment of a range of other cancers, including solid tumours, and beyond cancers such as for autoimmune conditions such as lupus.

Given such developments, it is plausible that CAR-T therapies may be clinically indicated for a range of cancers and other conditions in future. If this happens, it will likely increase the numbers of patients that could clinically benefit from such therapies.

CAR-T Therapies: Access for Patients in Europe?

However, despite the significant and potential health benefits, currently in Europe these therapies as provided under commercial pathways can cost on estimate over €300,000 per patient in direct costs alone, with further additional indirect costs including the costs of hospital stays, intensive care treatment etc. As a result of these high costs, public health systems may in some cases be unable to offer these therapies to all patients who may clinically benefit from them, and such costs are currently a key barrier to providing access.

Furthermore, where any therapies are funded by national public health systems at high costs, given finite national health budgets, this can give rise to ethical issues, including ‘opportunity costs’ as funding high-cost therapies such as CAR-T therapy can mean other therapies cannot be funded within a national public health system. Yet, for patients for whom CAR-T therapies are clinically indicated, this therapy may be their last and only treatment avenue, and therefore potentially lifesaving. This gives rise to difficult ethical considerations.

If the costs of CAR-T therapies remain at the same level, these issues could likely be exacerbated if the numbers of patients who may benefit from these therapies increase as is currently expected. It is, of course, plausible costs may reduce if there are more patients being treated with such therapies in future, however, this is not guaranteed.

Maximising Patient Benefits: Developing Further Pathways for Sustainable Access and Provision of CAR-T Therapies

To maximise the benefits these therapies can bring for patients, it is vital that there is deeper national and international consideration around how to develop more sustainable and affordable pathways to develop and provide CAR-T therapies in a safe and effective manner. As part of such discussions, two issues must be considered: 1) developing further novel reimbursement models to change the way public health systems reimburse these therapies at a national level; and alongside this, it is vital that we consider 2) developing sustainable longer-term strategies to reduce costs and provide such therapies in a more affordable manner. This latter avenue could include de-centralised production of CAR-T therapies which may also reduce time lags between cell extraction and re-infusion for patients; and providing greater funding and support for in-house academic development and production of CAR-T therapies in Europe. Furthermore, there needs to be greater consideration of issues which can affect the prices that can be charged for such therapies, including considering: how intellectual property rights over elements of CAR-T therapies and related technologies are operating and how such rights are being licensed and enforced currently, the extent to which IP licensing policies could be leveraged by funders and other groups to ensure greater equitable downstream accessibility and affordability of therapies developed, in a manner that also maintains incentives for the development of such therapies; and having greater transparency around the prices paid in each State for CAR-T therapies which is not currently in place.

In short, CAR-T therapies hold significant potential for healthcare, including, for previously untreatable or difficult to treat cancers. They are lifesaving for some patients. However, if we are to fully realise the benefits such therapies can offer for patients, as a matter of urgency, there needs to be much deeper consideration of novel reimbursement models, and of how we can develop and deliver more sustainable and affordable pathways to provide such therapies in all countries and to all patients who may benefit clinically from their use.

Authors: Aisling McMahon, Alanna Kells, and Sinéad Masterson

Affiliations: Maynooth University

Competing interests/acknowledgments:  This article is based on research conducted as part of the Irish Research Council funded, ‘Patients’ Access to Advanced Cancer Therapies: Ethics and Equity of Access’ (PAACT) project conducted in collaboration with Breakthrough Cancer Research. Views expressed and any errors or omissions are authors’ alone.