A Retrospective Study of Subtle and Chronic Neurological Findings from CART in an Ethnically Diverse, Real-world Cohort
Samantha Cheng1, Elizabeth Zeldin1, Kith Pradhan1, Nishi Shah2, Dennis Cooper2, Lauren Shapiro2, Kira Gritsman2, Katharine McNeill2, Mark Milstein3, R Alejandro Sica2
1Montefiore Medical Center/Albert Einstein College of Medicine, 2Medical Oncology, Montefiore Medical Center/Albert Einstein College of Medicine, 3Neurology, Montefiore Medical Center
Objective:
The objective was to identify risk factors, acute neurologic signs, and neurologic outcomes in a minority-rich cohort of patients treated with chimeric antigen receptor T-cell (CART) therapy.
Background:
Though CART has emerged as a revolutionary treatment for relapsed or refractory B-cell malignancies, immune effector cell-associated neurotoxicity syndrome (ICANS) remains a significant complication with little trial data in minority populations. There is also a lack of understanding of signs of acute neurotoxicity outside of ICANS grading criteria, as well as signs of prolonged neurotoxicity.
Design/Methods:
We conducted a retrospective study of patients with B-cell lymphoma who received axicabtagene ciloleucel CART between June 2018 and July 2022 at a minority-rich hospital. Demographics, baseline functional status, CNS involvement, progression-free survival (PFS), overall survival (OS), ICANS grade, neurological findings, and neurologic outcomes were recorded for analysis.
Results:
Our sample consisted of 49 patients with an ethnic composition of 17 Hispanic, 14 Caucasian, 13 African American, 2 Asian, and 3 unspecified/other patients. Median OS was 48 months and median PFS was 22.3 months. 19 (39%) patients had ICANS > 0. There was no association between ICANS and any of the following variables: ECOG, KPS, sex, age, ethnicity, CNS involvement.
Among the 19 patients with ICANS > 0, neurologic deficits were seen in attention (16), language (15), orientation (13), abnormal movements (6), and motor strength (4). 2 patients had persistent cognitive deficits, and 6 died during hospitalization. 4 patients with ICANS 0 had subtle findings including motor apraxia, decreased fine motor movements, tremors, and sensory changes. Of those patients, 2 reported persistent hand tremors.
Conclusions:
Out study supports a more nuanced neurological evaluation to identify subtle findings of neurotoxicity both peri-therapeutically and chronically. We also observed that 16% of cases experienced permanent neurotoxicity or death, a higher proportion than seen in clinical trials which do not traditionally enroll marginalized populations.
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