At the 66th American Society of Hematology (ASH) Annual Meeting and Exposition, Pharmacy Times® sat down with Jason Wang, MD, assistant professor at the Ohio State University Comprehensive Cancer Center to discuss an abstract he is presenting at a session on Sunday, December 8. The abstract is focused on the significant decrease in the severity and duration of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) associated with axicabtagene-ciloleucel (axi-cel; Yescarta) therapy in patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL).
Wang elaborates on the results of the analysis and the real-world implications for pharmacists treating patients in this population, including the benefits stemming from a reduction in steroid treatment duration due to axi-cel's effectiveness in these patients.
Key Takeaways
1. Reduced Severity of CRS and ICANS: There's been a significant decrease in the severity of both CRS and ICANS associated with axi-cel therapy in real-world patients with R/R LBCL.
2. Improved Patient Outcomes: Lower severity of these side effects leads to better patient outcomes, including reduced need for intensive care and shorter hospital stays.
3. Potential for Longer-Term Benefits: While long-term data is still being collected, the reduced toxicity profile of axi-cel may have positive implications for overall survival and quality of life for patients with B-cell lymphomas.
Pharmacy Times: Could you elaborate on the changes in protocols and management strategies that may have contributed to the observed decrease in CRS and ICANS severity and duration?
Jason Wang: What we observed in our study is there is a significant decrease in severe CRS, which means grade 3 or higher CRS, from 11% initially to 3% in most recent years. The study doesn't investigate details about the specifics on why this has happened, because this is mostly a descriptive study. But there's a couple of things that give us hints. One is more patients are getting bridging therapy, which we know is associated with lower tumor burden, which is associated with lower incidence of severe CRS. The other thing we know in our practice, is that we use more and more preemptive use of steroids and toclizumab (Actemra; Genentech) in earlier settings such as prolonged grade 1 CRS, which also may contribute to the lower incidences of these complications. Just from this study alone, it's very hard to draw any conclusions for this question.
Pharmacy Times: How do you anticipate these trends will impact the overall risk-benefit profile of axi-cel therapy, particularly for patients with comorbidities or advanced disease stages?
Wang: 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.
Pharmacy Times: What are the long-term implications of these reduced toxicities on patient quality of life and overall survival outcomes?
Wang: In our study, we don't have the data to look at the quality of life, but we do look at the overall survival (OS). But just keep in mind that the follow-up time-period for the most recent study period from 2022-to-2023 is very short, because right now, it's 2024. But we do notice that the OS was no different for 3 study periods.
Pharmacy Times: How might these changes in trends impact health care resource utilization among pharmacists and patient outcomes, especially considering the costs associated with the management of CRS and ICANS?
Wang: 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.
The 66th ASH Annual Meeting and Exposition takes place from Saturday, December 7 to Tuesday, December 10 in San Diego, California. You can follow our continuing coverage here.
Pharmacy Times: What should pharmacists know about the evolving strategies for management of axi-cel-related toxicities? Are there any emerging strategies or novel agents that may further optimize patient outcomes?
Wang: I think the strategy mainly can be 2 categories. One is what we call prophylactic. We use things like steroids or tociluzumab before the onset of CRS and ICANS. The other strategy is called preemptive, which is, we start steroids and tocilzumab very early in lower-grade CRS, like grade 1 CRS. I think these 2 categories have really made a difference in the safety profile for axi-cel.
