TOPLINE

Patients with relapsed/refractory large B-cell lymphoma (LBCL) who achieved optimal fludarabine exposure during lymphodepletion chemotherapy had better progression-free survival after chimeric antigen receptor (CAR) T-cell therapy than those who did not achieve optimal exposure.

METHODOLOGY

• Researchers conducted a prospective cohort study to assess whether fludarabine exposure during lymphodepletion chemotherapy was associated with CAR T-cell therapy outcomes in patients with LBCL.
• The final analysis included 54 patients with relapsed/refractory LBCL at a Spanish hospital between March 2021 and September 2022. The median age was 59 years, and 56% were men.
• Patients received manufacturer-recommended lymphodepletion with fludarabine and cyclophosphamide, with dosing that varied by CAR T-cell product (axicabtagene ciloleucel or tisagenlecleucel), followed by infusion after a 3- to 5-day washout period.
• Fludarabine exposure was measured using up to seven blood samples collected between the start of lymphodepletion and CAR T-cell infusion, with area under the curve (AUC) from time zero to last measurable concentration calculated using a population pharmacokinetics model.
• The primary endpoint was progression-free survival. Secondary endpoints included overall survival, response rates, and occurrence of toxicity-related events. The median follow-up duration was 24.5 months.

TAKEAWAY

• The optimal fludarabine exposure window was 17.5 to 21.5 mg·h/L for axicabtagene ciloleucel and 14.0 to 18.0 mg·h/L for tisagenlecleucel. Overall, 44% of patients fell within the optimal exposure window.
• Median PFS was not reached in the optimal exposure group compared with 13.3 months in the nonoptimal exposure group (P = .03).
• Optimal fludarabine AUC was associated with improved PFS in a multivariable analysis (hazard ratio, 0.31; P = .03).
• Overall survival, CAR T-cell expansion, and rates of cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, and hematologic toxicity did not differ significantly between the optimal and nonoptimal groups.

IN PRACTICE

"These findings highlight the importance of developing [pharmacokinetic] models in CAR T-cell patients and the need for accurate fludarabine concentration measurements to enable personalized dosing and optimize treatment outcomes," the authors wrote.

SOURCE

The study was led by Mario Andrés Sánchez-Salinas, Vall d'Hebron Institute of Oncology in Barcelona, Spain. It was published online on August 3 in Blood Advances.

LIMITATIONS

The study was conducted at a single center and had a relatively small sample size. Not all seven samples could be collected from every patient owing to scheduling challenges.

DISCLOSURES

The study was supported in part by the Carlos III Health Institute. Multiple authors reported receiving consulting fees, honoraria, or research support from pharmaceutical companies including Bristol Myers Squibb, Kite/Gilead, Janssen, Novartis, and others. Detailed author disclosures are reported in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.