Cognitive and Psychological Recovery from the Immune Effector Cell Associated Neurotoxicity Syndrome Following Chimeric Antigen Receptor T-Cell (CAR-T) Therapy

Introduction:

Chimeric antigen receptor T-cell therapy has become standard of care treatment for several types of haematological malignancies. Immune effector cell associated neurotoxicity syndrome (ICANS) is a serious side-effect, with diverse neurocognitive symptom presentation. ICANS is typically considered an acute condition, however, the recovery trajectory has not been well-defined. The study aimed to investigate cognitive and psychological recovery from ICANS in adult haematology patients over 1 year after CAR-T therapy.

Methods:

Twenty patients completed a comprehensive cognitive assessment and a self-report measure of psychopathology and cognitive concerns before receiving commercial CAR-T for treatment of lymphoma (95%) or leukaemia (5%). The assessment was repeated 1-month, 6-months, and 1-year post-CAR-T. Seven (35%) patients experienced ICANS acutely. Bayesian repeated measures analysis of covariance examined the effect of interaction between ICANS group and time of the assessment on change in cognition and psychopathology. Models were adjusted for age, education, and sex.

Results:

ICANS patients declined in executive function post-CAR-T, while non-ICANS patients remained stable (BF₁₀=524.0). The ICANS group had lower mean scores at the 1-month review (BF₁₀=9.5, η²=0.4). No group difference was detected at 6-months or 1-year. Three (43%) ICANS patients had a clinically evident executive function impairment at 1-month, returning to baseline at 6-months and remaining normal at 1-year. In the non-ICANS group, all patients had normal executive function across all assessments. There was no evidence for an effect of ICANS group over time in any other cognitive domain. Analyses of individual psychometric measures, revealed evidence for an effect of ICANS group over time for tests of strategic lexical retrieval (BF₁₀=8.1), verbal memory (BF₁₀=67.3), and auditory attention span (BF₁₀=9.2). The lowest mean scores were observed at 1-month in the ICANS group. There was no change in patient-reported cognitive concerns or symptoms of psychopathology over time, irrespective of ICANS group.

Conclusions:

ICANS patients had a reduction in executive function, verbal memory, and the auditory attention span 1-month post-CAR-T. There was no effect of ICANS on cognitive change at 6-months or 1-year, suggesting complete resolution of cognitive manifestation of ICANS. Stable self-reported symptoms of psychopathology indicate good psychological tolerance of neurological toxicity. Our findings provide a positive outlook for long-term cognitive recovery following CAR-T therapy. Cognitive monitoring, however, is indicated for ICANS patients for up to 6-months post-infusion.

van der Linde:Kite: Honoraria. Roos:Roche: Consultancy, Honoraria, Other: conference travel support ; MS Australia and the Trish Multiple Sclerosis Research Foundation: Research Funding; Novartis: Consultancy, Honoraria, Other: conference travel support; Merck: Consultancy, Honoraria, Other: conference travel support; Biogen: Consultancy, Honoraria, Other: conference travel support. Loi:Otsuka: Honoraria; National Health and Medical Research Council: Research Funding; Lundbeck: Honoraria. Dowling:Abbvie: Patents & Royalties; Novartis: Consultancy; Kite/Gilead: Consultancy. Dickinson:Adicet Bio: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Speakers Bureau; Gilead: Consultancy, Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria, Speakers Bureau; Genmab: Consultancy, Honoraria, Speakers Bureau; Kite: Consultancy, Honoraria, Speakers Bureau. Kalincik:MS International Federation and World Health Organisation: Consultancy; WebMD Global: Honoraria, Other: conference travel support; Genzyme: Research Funding; BMS: Consultancy; Roche: Consultancy, Honoraria, Other: conference travel support; Janssen: Consultancy; Sanofi Genzyme: Consultancy, Honoraria, Other: conference travel support; Novartis: Consultancy, Honoraria, Other: conference travel support, Research Funding; Merck: Consultancy, Honoraria, Other: conference travel support, Research Funding; Biogen: Consultancy, Honoraria, Other: conference travel support, Research Funding; Eisai: Honoraria, Other: conference travel support; Teva: Honoraria, Other: conference travel support; BioCSL: Honoraria, Other: conference travel support ; Celgene: Research Funding. Harrison:Celgene/BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen Cilag: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Haematologix: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Genetech: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Eusa: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Terumo BCT: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Malpas:Merck: Other: conference travel support ; the National Health and Medical Research Council: Research Funding; Biogen: Other: conference travel support; Novartis: Other: conference travel support; Dementia Australia: Research Funding; Multiple Sclerosis Australia: Research Funding; The Royal Melbourne Hospital Neuroscience Foundation: Research Funding. Anderson:ALLG CLL Working Group Co‐Chair: Membership on an entity's Board of Directors or advisory committees; Sobi: Membership on an entity's Board of Directors or advisory committees; BeiGene: Honoraria; Janssen: Honoraria; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support; Kite Gilead: Honoraria; Sanofi: Honoraria; CSL: Honoraria; Takeda: Honoraria; Novartis: Honoraria; Roche: Honoraria; NHMRC: Research Funding.