(L-R) Dr. Jennifer Bell, lead author of the study and Dr. Christine Chen, senior author of the study.
By: Mimi Yuejun Guo, Communication Specialist, Princess Margaret Cancer Centre, University Health Network and Robyn Rosenfeld, Communications Specialist, Research Communication at University Health Network
“A decision for CAR-T is a decision about patient access to a potentially life-saving therapy. It cannot be taken lightly," says Dr. Jennifer Bell, Senior Bioethicist at University Health Network.
Chimeric antigen receptor T-cell therapy (CAR-T) is a breakthrough therapy for the treatment of advanced blood cancers. It has the potential to cure or prolong the patient's life expectancy when facing a dire situation with no other treatment options. In 2023, 60 adult patients at Princess Margaret Cancer Centre (PM) received the therapy, and the demand for this therapy is on the rise.
However, barriers, such as a limited number of treatment centres, the steep cost, and the need for specialized resources, prevent CAR-T from being used widely.
In Ontario, only three centers provide CAR-T therapy for adult patients. Several CAR-T products, which cost about $500K, can be covered by Ontario Health funding if the patient meets the eligibility requirements set by Health Canada, but the clinical care cost remains substantial at the institutional level, with the need for inpatient beds, cell collection and laboratory facilities, specially trained clinical staff and more.
Apart from high institutional resource use, CAR-T manufacturing may also pose a challenge. Patient T cells are collected at one of the three centres and shipped to a manufacturing location in the U.S. to be genetically engineered into CAR-T cells that can target cancer cells, before they are shipped back and infused into patients.
As demand for CAR-T treatment outpaces manufacturing capabilities and healthcare infrastructure, this creates a dilemma for clinical care providers, forcing them to decide which patient receives the next coveted treatment spot.
“Currently, there is no clear prioritization framework. Oftentimes, the patient who gets pushed to the top of the list for the next spot is the one with the most vocal advocate," says Dr. Christine Chen, Clinical Director of the Cell Therapy Program at PM. “There is an urgent need to set up a formal process to review all the factors that should be weighed when deciding on priority."
Researchers at UHN led by Drs. Jennifer Bell and Christine Chen have identified these factors in a research paper and proposed a three-step ethical process to equitably prioritize patients in need of CAR-T.
The first step of the process starts with medical experts at the disease site assessing the medical benefits of receiving CAR-T based on specific patient conditions.
If there is any potential for any medical benefits, then the second step is to evaluate the patients' safety risk for potential adverse effects and identify psychosocial factors that might be barriers for patients to adhere to the therapy.
Since patients need to spend one to two weeks in the hospital after CAR-T infusion, and then stay close to the hospital for at least 30 days to monitor adverse effects. The psychosocial factors can include caregiver support and extra translation support etc.
The third step is a final discussion for prioritization, using the factors weighed in each prior step, but also incorporating medical urgency, such as how fast the patient is deteriorating. Performed by a multi-disciplinary Cell Therapy Review Committee, the discussion is to allow for a transparent process and fulsome consideration of all patients awaiting CAR-T.
“This process is not meant to determine access or exclusion from CAR-T, but rather to prioritize the order in which patients proceed. For example, someone with a high likelihood of cure with a rapid pace of disease who is fit and functional, might jump ahead of someone less fit, perhaps suffering from prior chemo toxicities, and requiring optimized care before CAR-T," Dr. Chen clarifies.
“It strengthens patient trust in the health care system by ensuring decision-making is fair and transparent, inclusive of patient input with the opportunity for appeals," adds Dr. Bell.
The researchers are sharing these decision-making tools openly, encouraging other institutions to adapt them for their unique circumstances. The goal is to promote justice in resource allocation for all potential CAR-T candidates in Canada and globally, fostering further research in this area to support fair access to life-saving therapies.
“We hope this framework can enhance a national discussion so that it doesn't matter if you are in northern Manitoba, or if you are in downtown Toronto, you have equitable access to CAR-T cell therapy in Canada," says Dr. Bell.
Acknowledgement
This research work was supported by UHN Foundation.
Scientist Affiliation
Dr. Jennifer Bell is a Clinician Investigator in the Supportive Care Department at Princess Margaret Cancer Centre, a Senior Bioethicist in the Department of Clinical and Organizational Ethics at University Health Network, Education Investigator 2 at The Institute of Education Research (TIER) and an Assistant Professor in Psychiatry and Member of the Joint Centre for Bioethics at the University of Toronto (UofT). Dr. Christine Chen is the Clinical Director of the Cell Therapy Program, a Clinician Investigator at Princess Margaret Cancer Centre, and an Associate Professor in the Department of Medicine at UofT.
Reference study
Bell JAH, Jeffries GA, Chen CI. Mitigating inequity: ethically prioritizing patients for CAR T-cell therapy. Blood. 2023 Oct 12;142(15):1263-1270. doi: 10.1182/blood.2023020703. PMID: 37540818.
Additional Information
Equity in cancer care is important in Canada and is the theme of 2024's World Cancer Day (Feb 4): “Closing the Care Gap". This feature was created to join the call to action and to promote health equity, enhance cancer service accessibility, and to close the care gap.
What can health system partners learn from this story?
The framework provides a tool for other cancer centres to adopt and adapt for allocating CAR-T resources.
What is the key takeaway, lesson learned or best practice?
This ethical framework in the research paper was built upon an approach called Accountability for Reasonableness (A4R). A4R can guide decision-making and bring procedural justice in the context of resource scarcity, not only for CAR-T.
“In a society where, different people have different values and it may be hard to come to an agreement, what we can do is to engage in a fair and democratic process to arrive at a decision," says Dr. Bell. “A4R is a process to make sure different voices and perspectives are being heard. It has been used extensively in other health care situations such as vaccine allocation during the coronavirus pandemic."