A panel of distinguished experts at Fred Hutchinson Cancer Center recently convened to examine the evolving landscape of CAR T-cell therapy in treating large-cell lymphoma, focusing particularly on two leading treatments: axicabtagene ciloleucel (Yescarta) and lisocabtagene maraleucel (Breyanzi).
Safety Profiles and Clinical Considerations
The discussion, led by Dr. Mazyar Shadman, Medical Director at the Bezos Family Immunotherapy Clinic, revealed important distinctions between the two CAR T-cell products. Experts noted that lisocabtagene maraleucel (liso-cel) appears to demonstrate a more favorable safety profile, though this observation comes with important caveats regarding study design differences.
Dr. Christina Poh highlighted that while liso-cel shows lower toxicity rates, the TRANSFORM trial's design allowed for bridging therapy, potentially affecting the adverse event profile. "Based on the data, it seems like liso-cel is safer and less toxic, but the study design is a little different," Dr. Poh noted.
Manufacturing and Logistics
Significant differences exist in manufacturing timelines between the two products. Lisa Getzendaner, MHS, PA-C, reported that axi-cel typically requires 2.5-3 weeks for manufacturing, while liso-cel takes 4-5 weeks. Production slot availability has not been a limiting factor for either product, though out-of-specification products can cause additional delays.
Disease Burden Impact
Recent research published in Blood has demonstrated the importance of metabolic tumor volume (MTV) in predicting treatment outcomes. The ZUMA-7 trial, which did not allow bridging therapy, showed that pre-treatment disease burden significantly influences patient outcomes. Dr. Brian Till explained that this finding provides valuable insights for patient selection and timing of therapy.
Treatment Selection Considerations
The panel emphasized that treatment selection involves multiple factors beyond just efficacy data:
- Patient location and access to care facilities
- Caregiver availability
- Social support systems
- Need for inpatient vs. outpatient administration
Outpatient Management
The discussion touched on the complexities of outpatient CAR T-cell therapy administration. Dr. Chaitra Ujjani noted that while outpatient delivery might improve access for some patients, it can create additional challenges due to caregiver requirements and the need for close monitoring of potential complications like cytokine release syndrome.
Quality Control and Product Specifications
Recent modifications to FDA specifications for liso-cel have improved manufacturing success rates. Dr. Till noted that comparative data between in-specification and out-of-specification products showed similar safety and efficacy profiles, leading to adjusted manufacturing parameters that now achieve approximately 90% specification compliance.
The experts concluded that both products remain valuable options for large-cell lymphoma treatment, with selection depending on individual patient factors, institutional experience, and specific clinical scenarios. The ongoing refinement of patient selection criteria and management protocols continues to optimize outcomes for both therapies.
