A recent study published in Blood Advances suggests that current FDA Risk Evaluation and Mitigation Strategy (REMS) mandates for CAR T-cell therapy may be more restrictive than necessary, potentially hindering patient access. The research, which assessed the onset and duration of toxicities post-CAR T infusion, indicates that a shorter, more flexible monitoring period could be implemented without compromising patient safety.
The study, led by Dr. Nausheen Ahmed from the University of Kansas Medical Center, retrospectively analyzed data from 475 patients with non-Hodgkin lymphoma who received axicabtagene ciloleucel (Yescarta), tisagenlecleucel (Kymriah), or lisocabtagene maraleucel (Breyanzi). The primary aim was to determine the incidence of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) beyond the initial weeks following CAR T-cell infusion.
Key Findings on Toxicity Onset
The analysis revealed that after the first two weeks post-infusion, the incidence of CRS was 0%, and ICANS occurred in approximately 1% of patients. These findings suggest that the most critical period for monitoring these toxicities is within the first 14 days. Dr. Ahmed noted that current REMS mandates require patients to remain within two hours of the treatment center for up to four weeks and avoid driving for eight weeks, which can create significant physical and financial burdens.
Proposed Changes to Monitoring Guidelines
Based on these data, the researchers propose a revised monitoring approach. They suggest a mandatory two-week monitoring period near the specialized care center, followed by a collaborative assessment to determine the patient's individualized needs beyond that period. This flexible approach aims to reduce the burden on patients while ensuring timely intervention if complications arise.
Impact on Patient Accessibility
The current REMS mandates can disproportionately affect patients from lower socioeconomic backgrounds, ethnic and racial minority groups, and those living far from treatment centers. By reducing the mandatory monitoring period, the financial and logistical challenges associated with CAR T-cell therapy could be alleviated, potentially improving access for these underserved populations. Dr. Ahmed's previous work has highlighted these disparities, demonstrating that patients living more than two hours from a treatment center are less likely to receive CAR T-cell therapy.
Causes of Death and Continuum of Care
The study also examined causes of death within the first 90 days post-CAR T infusion. Within the first four weeks, neurotoxicity and infections were the primary causes of death. Beyond four weeks, infections remained a significant concern. These findings underscore the importance of a collaborative approach between specialized care centers and referring physicians to ensure continuous and comprehensive patient care.
Broader Implications for CAR T-cell Therapy
While the study focused on lymphoma, Dr. Ahmed's group has also investigated toxicity profiles in multiple myeloma patients receiving idecabtagene vicleucel (Abecma) and ciltacabtagene autoleucel (Carvykti). Their findings indicate a similar pattern, with a low incidence of CRS and ICANS after the initial two-week period. Additionally, they identified hemophagocytic syndrome as a potential adverse event associated with CAR T-cell therapy in myeloma patients.
Addressing Concerns About Secondary Malignancies
Recent concerns have emerged regarding the potential for secondary malignancies following CAR T-cell therapy. While the study's follow-up period was limited to 90 days, Dr. Ahmed acknowledged the importance of long-term monitoring for the development of myelodysplasia, leukemia, and skin cancers. Despite these risks, she emphasized that the benefits of CAR T-cell therapy in lymphoma and myeloma often outweigh the potential risks, particularly when compared to other treatment options. Patients should be fully informed about these risks when considering CAR T-cell therapy.
The Path Forward
The next step is for the FDA to review the data and consider revising the REMS mandates. A more flexible, individualized approach to monitoring could significantly improve patient access to this potentially life-saving therapy while maintaining a strong focus on patient safety and outcomes.
