Personalized medicines, such as Chimeric Antigen Receptor -T cell (CAR-T) therapy, represent a significant leap in scientific innovation that was once thought to be almost impossible. This therapy has revolutionized cancer treatment and offered hope to patients who once had none. It is premised on re-engineering a patient’s T cells to specifically target cancer cells. But, with any jump in innovation comes inevitable growing pains – some new and some old, that were somewhat hidden or resolved but need to be re-evaluated for CAR-T therapies. These growing pains will need to be addressed as the use of these therapies expands.

Currently in Canada, there are six approved CAR-T therapies. These therapies are used to treat B-cell leukemia and lymphoma, mantle cell leukemia, and multiple myeloma.¹ They are also generally considered a last-line therapy, that is therapies that are used only after other, less expensive, treatments have failed.² Although six may seem like a relatively small number of approved therapies that are accessible to only a few patients, this number will grow exponentially in the coming years. Currently, there are 1,652 clinical trials involving CAR-T cells registered on clinicaltrials.gov. While it is easy to get lost in the promise of CAR-T therapy, clinicians and researchers need to take a step back to consider the ethical ramifications of these therapies. With any precision medicine comes concerns over how racial categories, geographical barriers, genetic differences, and more may overlap in ways that produce significant differences in medical outcomes and in availability of the technology. This blog post brings into focus race-disparate effects of CAR-T therapy, namely in the enrollment in clinical trials, the likelihood of seeking out the therapy due to systemic barriers, and adverse events upon treatment. It is important to keep these issues at the forefront as research continues and seeks to expand the reach of CAR-T therapies to other cancers and tumour types.

For a drug to be approved, clinical trials must be done. The issues with clinical trial enrollment is not a new topic, but has been the focus of criticism for CAR-T therapy trials. Overall, there is a lack of visibility, representation, and diversity. In a review of patients enrolled in CAR-T trials in 2022, the statistics were shocking. 71.2% of patients enrolled in these trials were white, with a mere 5.6% being African American, 5.3% being non-white Hispanic, and 3.7% being Asian.³ These numbers are far from the demographics in society. As CAR-T therapy is an individualized treatment, more needs to be done to understand how these treatments affect minority patients. This is all the more pressing as there is research that indicates that certain groups of patients are more likely to have severe adverse events while receiving CAR-T treatment than other groups. A prime example of this is the prominence of severe cytokine release syndrome (CRS) in Hispanic patients. In the study first revealing this, Hispanic patients were shown to have greater than three times the odds of experiencing grade 3 or higher CRS as compared to White patients.⁴

When CRS is severe, it often requires treatment in comprehensive intensive care units. This further serves to limit the availability to CAR-T therapies to patients not located in urban areas.⁵ In Quebec, the only CAR-T treatment centers are located in Montreal and Quebec City and in Ontario, the treatment centers are located in Toronto and Ottawa.⁶ There are other factors that hinder a patient’s likelihood to seek out CAR-T therapies, such as non-referral or lack of timely referral, patient hesitancy (a factor seen during the COVID-19 pandemic as well), poor understanding of the therapy, lack of caregiver support, and more. Even in the Canadian context where CAR-T therapies are covered as last-line therapies, it has been shown that individuals or families with an income under $40,000 almost never seek out the treatment.⁷

This quick overview of the race-disparate effects and availability of CAR-T therapy is not meant to depress, but rather to serve as a call to action for ethicists, policymakers, researchers, clinicians, and others. As CAR-T therapies expand to possibly treat cancers beyond blood cancers, clinical trial enrollment and issues with access and diversity should remain front of mind. This means ensuring wider recruitment efforts, remembering to consider language accessibility in clinical trial design, providing support to patient associations in discussions with policymakers and government officials regarding access to these therapies, and more. It is also important to keep in mind that hesitancy in healthcare affects patient recruitment for all clinical trials, not just CAR-T trials. After all, the more diverse the trials, the more data can be pointed to assure patients that clinicians know how these therapies work in all patients.