The U.S. Food and Drug Administration (FDA) recently lifted its Risk Evaluation and Mitigation Strategies (REMS) designation for CAR T-cell therapies, a move that reflects growing confidence in the safety protocols developed around these treatments. Despite this regulatory shift, access to CAR T therapies remains limited, with only about 30% of eligible patients able to receive them.
A clinical pharmacist and biotech executive, currently serving as CEO of CytoAgents, commented on the significance of the FDA's decision and the ongoing challenges facing CAR T therapy: "As a clinical pharmacist and biotech executive with more than 20 years of experience in healthcare, I’ve seen the transformative impact of CAR T—and the risks that can keep patients from fully benefiting from it. In my current role as CEO of CytoAgents, which develops therapies to manage cytokine-driven toxicities, I’m focused on finding safer, more-effective ways to mitigate CAR T’s most serious side effects. This role has given me a frontrow seat to observe why the FDA’s action is important, and what action is still needed."
CAR T-cell therapy has provided durable remissions for some cancer patients but is also associated with significant risks such as cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS). These complications are both common and severe; approximately 70% to 95% of CAR T recipients develop CRS, while about half experience ICANS. Up to one-third of those affected by these side effects require intensive care unit admission.
Current management strategies rely on intravenous corticosteroids and monoclonal antibodies like tocilizumab, but these interventions can lead to additional health problems such as infections or muscle weakness caused by steroids. The CEO noted: "Clinicians use intravenous corticosteroids and tocilizumab, a monoclonal antibody that inhibits interleukin-6, to fight CRS and ICANS. However, these treatments present their own risks, including serious infections and steroid-induced myopathies. We need better alternatives, and quickly."
Access barriers are further compounded by the complexity of managing toxicities associated with CAR T therapy. Treatment is often restricted to academic medical centers equipped for intensive monitoring—an arrangement that limits availability due to bed space constraints and geographical distance for many patients.
"There has been limited investment in finding better ways to control them," said the CEO regarding efforts to address side effects. "In some ways, CAR T suffers from its own success... But it’s incredibly important that the biopharma industry take a hard look at what goes wrong with CAR T and develop better therapeutic responses."
One potential solution involves developing oral treatments that could reduce reliance on steroids—such as CTO1681 being trialed by CytoAgents—which might allow for broader use in community hospitals or outpatient settings.
Looking ahead, experts anticipate increased demand for effective toxicity management solutions as research continues into expanding CAR T applications beyond blood cancers into solid tumors. Hundreds of new cell therapies are currently under investigation in clinical trials.
"Ultimately, by minimizing CAR T’s associated toxicities, we can open up bed space, move some of these therapies into outpatient and community settings and, most importantly, maximize patient access," concluded the CEO.
