Neurocognitive testing to predict ICANS post-CAR T.
Authors: Wesson William , Scott Lauren , Suleman Nahid , DeJarnette Shaun , Abdallah Al-Ola A. , Lutfi Forat Umair , Abhyankar Sunil H. , Shune Leyla , Mushtaq Muhammad Umair , Singh Anurag Kumar , Abdelhakim Haitham , McGuirk Joseph , Nashatizadeh Muhammad , Muenks Elizabeth M , Katz Hannah , Ahmed Nausheen 
Published: June 2024

e19003

Background: Since the approvals of chimeric antigen receptor T-cell (CAR T) therapy in acute lymphoblastic leukemia (ALL), non-Hodgkin lymphoma (NHL), and multiple myeloma (MM), it has been increasingly offered in centers nationwide. Immune effector cell-associated neurotoxicity syndrome (ICANS) poses a potentially fatal risk with CAR-T. Identifying patients at risk of having high grade ICANS is a thus a priority. Scoring systems such as the EASIX scores have accounted for disease and comorbidity factors but haven’t addressed neurocognitive function. The St. Louis University Mental Status (SLUMS) Exam and the Montreal Cognitive Assessment (MoCA) have not been examined for validity and reliability in this population, so we performed a retrospective review of CAR T patients at the University of Kansas Medical Center to identify if incidence or severity of ICANS could be correlated with neurocognitive testing performed in the pre-infusion period. Methods: Patients receiving CAR T targeting CD19 or BCMA between December 2017 and December 2023 were included. Neurocognitive testing was performed by trained onco-psychology, neurology, or hematology-oncology staff. The SLUMS exam is an 11 question exam scored on a 30 point scale to predict normal neurocognitive function (27-30 points), mild neurocognitive disorders (21-26 points), and dementia (0-20 points). The MoCA is an 11 question exam scored on a 30 point scale to predict normal cognition (26-30 points), mild cognitive impairment (18-25 points), moderate cognitive impairment (10-17 points), and severe cognitive impairment (<10 points). Incidence of ICANS and severity of ICANS were compared between patients who had any detected cognitive dysfunction and those who had none, as well as between the tiered result system unique to each test. Results: We included 360 patients in this analysis, (257 NHL, 84 MM and 19 ALL) leading to comparisons of 276 CD19-directed CAR T patients and 84 BCMA-directed CAR T patients. In CD19-directed patients, there were no differences in ICANS incidence according to the SLUMS scores. There was a significant increase in ICANS incidence for patients who had a positive MoCA exam, p=0.006. Additionally, ICANS incidence was correlated with more severe MoCA results, p=0.01. No differences in ICANS severity were observed using any neurocognitive test. In BCMA-directed patients, no differences in ICANS were observed using the SLUMS or MoCA. Conclusions: Our results suggest that while the SLUMS exam does not predict ICANS, the MoCA may independently predict incidence of ICANS. Patients with a higher score correlating with normal cognition are less likely to develop ICANS and may be appropriate for outpatient therapy. For those with lower scores correlating with more severe neurocognitive disorders, inpatient monitoring and early intervention will continue to be important.