Clinical Pharmacology of Lisocabtagene Maraleucel in B-cell Malignancies

Chimeric antigen receptor (CAR) T-cell therapies represent a distinct therapeutic modality whose clinical activity is governed by in vivo cellular kinetics. Lisocabtagene maraleucel (liso-cel) is an autologous CD19-directed, 4-1BB CAR T-cell product in which in vivo expansion plays an important role in clinical pharmacology assessments. Across B-cell malignancies, characterization of liso-cel cellular kinetics demonstrates substantial interindividual variability in expansion, with no single evaluated clinical covariate exerting a clinically meaningful effect. Higher in vivo expansion has been associated with both efficacy and safety outcomes; however, interpretation of these relationships requires careful consideration of end point selection, baseline confounding, and outcome-specific biological context. Particularly, expansion–efficacy relationships are associative rather than causal and are influenced by baseline clinical characteristics and how efficacy end points are defined and assessed. Expansion–safety relationships are end point-dependent, reflecting dynamic immune interactions in the setting of cytokine release syndrome and predominantly downstream toxicity for neurological events. Other clinical pharmacology considerations, including retreatment, persistence, B-cell aplasia, and immunogenicity, further inform the interpretation of liso‑cel expansion within a broader clinical and biological framework. Collectively, these findings indicate that assessing in vivo liso-cel expansion provides important contextual clinical pharmacology information but does not establish it as an independent or deterministic driver of clinical outcomes.