Patient-reported outcomes and neurotoxicity markers in patients treated with bispecific LV20.19 CAR T cell therapy.

Background: With the rising number of chimeric antigen receptor (CAR) T cell treated patients, it is increasingly important to understand the treatment's impact on patient-reported outcomes (PROs) and, ideally, identify biomarkers of central nervous system (CNS) adverse effects.
Methods: The purpose of this exploratory study was to assess short-term PROs and serum kynurenine metabolites for associated neurotoxicity among patients treated in an anti-CD20, anti-CD19 (LV20.19) CAR T cell phase I clinical trial (NCT03019055). Fifteen CAR T treated patients from the parent trial provided serum samples and self-report surveys 15 days before and 14, 28, and 90 days after treatment.
Results: Blood kynurenine concentrations increased over time in patients with evidence of neurotoxicity ( p  = 0.004) and were increased in self-reported depression ( r  = 0.52, p  = 0.002). Depression improved after CAR T infusion ( p  = 0.035). Elevated 3-hydroxyanthranilic acid (3HAA) concentrations prior to cell infusion were also predictive of neurotoxicity onset ( p  = 0.031), suggesting it is a biomarker of neurotoxicity following CAR T cell therapy.
Conclusions: Elevated levels of kynurenine pathway metabolites among CAR T cell recipients are associated with depressed mood and neurotoxicity. Findings from this exploratory study are preliminary and warrant validation in a larger cohort.
Competing Interests: Competing interestsThe authors declare the following competing interests. P.H. reports receiving honoraria from Incyte, BMS, Legend, Jannsen, Takeda, Amgen, Karyopharm, GSK, Pfizer. C.J.H. is a member of the Scientific Advisory Boards of Phytecs, Inc, and has equity in Formulate Biosciences. B.J. reports receiving research support and honoraria and travel support from Miltenyi Biotec. D.S. and B.D. are authors on a patent for the 20.19 CAR. N.N.S. reports receiving honoraria and/or travel support from Incyte, Celgene, Lily, and Miltenyi Biotec; serving on scientific advisory boards for Lily, Kite, Celgene, Legend, Epizyme, Seattle Genetics, and TG therapeutics; equity ownership in Exelixis, Geron; receiving institutional research support for clinical trials from Miltenyi Biotec. The remaining authors declare no competing interests.
(© The Author(s) 2022.)