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Leo I. Gordon, MD, FACP


AACR 2022: Pharmacologic Attributes of Axicabtagene Ciloleucel and Therapeutic Index in Lymphoma

By: Vanessa A. Carter, BS
Posted: Wednesday, April 27, 2022

Jason R. Westin, MD, FACP, of The University of Texas MD Anderson Cancer Center, Houston, and colleagues delved deeper into the phase III ZUMA-7 trial, evaluating the pharmacokinetics, pharmacodynamics, and product attributes of axicabtagene ciloleucel in patients with large B-cell lymphoma (LBCL) in an attempt to improve its therapeutic index. Previous results of this study demonstrated the superiority of this chimeric antigen receptor (CAR) T-cell therapy over standard second-line therapy in terms of both event-free survival and objective response rate, Details on the more recent pharmacologic analysis were presented during the American Association for Cancer Research (AACR) Annual Meeting 2022 (Abstract CT004).

“Preinfusion axicabtagene ciloleucel features and postinfusion pharmacokinetic/pharmacodynamic profiles in [this] trial were associated with safety and efficacy outcomes and supported that optimizing product composition toward a juvenile T-cell phenotype may improve [its] therapeutic index,” stated the investigators. “These findings could result in future trials to evaluate if preemptive interventions, including enrichment of naive T cells in the product, could improve outcomes.”

This global study focused on samples from 170 patients who received axicabtagene ciloleucel. The T-cell composition (naive, CCR7-positive CD45RA-positive; differentiated, CCR7-negative), pharmacokinetic, and pharmacodynamic profiles of this agent were assessed for efficacy and safety.

The median peak CAR T-cell level was 25.8 cells/μL, and it took 8 days to reach the peak. Interestingly, the 28-day area under the curve and CAR T-cell peak were associated with a higher objective response rate (P = .0224) and increased grade 3 neurologic events (P = .0006). Additionally, rapid transient increases in serum analytes occurred early and seemed to correlate with increased high-grade neurologic events and cytokine-release syndrome.

Increased objective response rate, event-free survival, and complete response were influenced by infusion products that were richer in naive-like T cells expressing CD27 and CD28. In contrast, products richer in differentiated T cells and with lower in CCR7-positive CD45RA-positive T cells were associated with higher peak levels after infusion of various proinflammatory and immunomodulatory serum analytes.

Disclosure: For full disclosures of the study authors, visit

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