The 66th American Society of Hematology (ASH) Annual Meeting and Exposition featured discussions on the evolving landscape of CAR-T cell therapy, particularly regarding the management of toxicities associated with axicabtagene ciloleucel (axi-cel; Yescarta) in patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL). Jason Wang, MD, from the Ohio State University Comprehensive Cancer Center, presented findings on the decreased incidence and severity of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) following axi-cel treatment.
Decreased Severity of CRS and ICANS
Wang's analysis revealed a significant reduction in the severity of CRS, with grade 3 or higher CRS decreasing from 11% to 3% in recent years. This improvement is attributed to several factors, including increased use of bridging therapy to reduce tumor burden and the preemptive use of steroids and tocilizumab in earlier stages of CRS. “More patients are getting bridging therapy, which we know is associated with lower tumor burden, which is associated with lower incidence of severe CRS,” Wang noted. He also added, “The other thing we know in our practice, is that we use more and more preemptive use of steroids and toclizumab in earlier settings such as prolonged grade 1 CRS, which also may contribute to the lower incidences of these complications.”
Impact on Patient Outcomes and Healthcare Resource Utilization
The reduced severity of CRS and ICANS has a positive impact on patient outcomes and healthcare resource utilization. Patients experiencing less severe toxicities require less intensive care, shorter hospital stays, and reduced use of prolonged steroid courses. This not only benefits patients but also reduces healthcare costs. “Especially for high-grade CRS, like grade 3 or higher, is they are usually associated with ICU admission, use of prolonged course of steroids, which increase the cost for the patients. Right now, what we observe is a dramatic decrease in severe CRS, which means the patient doesn't have to stay in the ICU, they don't have to be on prolonged steroids for a long time, which is a benefit for us and for the patient as well,” Wang explained.
Long-Term Implications and Evolving Management Strategies
While long-term data on quality of life is still being collected, initial overall survival (OS) data suggests no significant difference across study periods. This indicates that the reduced toxicity profile of axi-cel does not compromise its effectiveness. Evolving management strategies focus on prophylactic and preemptive interventions. Prophylactic strategies involve using steroids or tocilizumab before the onset of CRS and ICANS, while preemptive strategies involve initiating these treatments early in lower-grade CRS. According to Wang, “I think the strategy mainly can be 2 categories. One is what we call prophylactic...The other strategy is called preemptive...I think these 2 categories have really made a difference in the safety profile for axi-cel.”
Implications for Patients with Comorbidities
The improved safety profile of axi-cel broadens its applicability to patients with comorbidities or advanced disease stages. With a lower incidence of severe CRS and ICANS, more patients can safely receive this potentially life-saving therapy. When axi-cel was first approved by the FDA in 2017, it had about a 90% incidence of CRS and 11% incidence of grade 3 or higher. But in recent years, we saw a steady decrease in the trend of that, which means more patients can more safely get this medication for B-cell lymphoma, which is great progress for the field.
