Axicabtagene Ciloleucel for the Treatment of B-Cell Lymphoma- Gaps, Opportunities and Future Perspectives
Author(s)
Karanth D, Dutta B, Mahapatra S, John A
Evalueserve, Bangalore, KA, India
Presentation Documents
OBJECTIVES: Axicabtagene ciloleucel (axi-cel; KTE-C19) is an engineered autologous anti-CD19 chimeric antigen receptor T cell therapy (CAR T-cell therapy) being used for the treatment of relapsed or refractory B-cell lymphomas (BCLs). Axi-cel therapy has proven to be better compared to the standard of care (SOC) therapy, like a high dose of platinum-containing salvage regimens or autologous stem cell transplantation. To improve potency and reduce toxicity with axi-cel therapy, cell product composition can be tweaked. We aim to discuss the recent advances in axi-cel therapy and suggest future considerations.
METHODS: A comprehensive literature search across various publicly available databases.
RESULTS: The currently available treatment option with phosphatidylinositol 3-kinase (Pi3K) inhibitors or other novel agents have achieved some degree of clinical activity. However, short remission with cure remain elusive. Axi-cel when tested as a front-line therapy in ZUMA-12 trial has shown higher objective response and complete response compared to the ZUMA-1 trial. Axi-cel product with a higher proportion of naïve, central and effector memory T-cell has led to superior growth following infusion. To reduce resistance and improve CAR T cell antigen recognition, bispecific and trivalent CARs targeting Tumor-Associated Antigen (TAA) have been developed.
While axi-cel is promising, it has some challenges like manufacturing errors, product variation, contamination and high cost. This challenge can be mitigated by scaling up CART cell therapy manufacturing, facilitated by advances in automated technology. Shifting from autologous to allogeneic cell sources enhances accessibility to axi-cel therapy and lowers treatment administration complexity and time. Further, generating CAR-T cells through genome editing with CRISPR/Cas9 can overcome issues like allogeneic response, cell fatigue, and toxicity.CONCLUSIONS: Future long-term clinical trials and real-world data should be conducted to demonstrate T cells with optimal in vivo fitness, durable persistence and efficacy.
Conference/Value in Health Info
Value in Health, Volume 25, Issue 12S (December 2022)
Code
CO126
Topic
Clinical Outcomes
Topic Subcategory
Comparative Effectiveness or Efficacy
Disease
SDC: Oncology