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Papers of the Week

2020 Jan

Biol Blood Marrow Transplant



Patient-Reported Neuropsychiatric Outcomes of Long-Term Survivors after Chimeric Antigen Receptor-T Cell Therapy.


Ruark J, Mullane E, Cleary N, Cordeiro A, Bezerra ED, Wu V, Voutsinas J, Shaw BE, Flynn K, Lee SJ, Turtle CJ, Maloney DG, Fann JR, Bar M
Biol Blood Marrow Transplant. 2020 Jan; 26(1):34-43.
PMID: 31605820.


CD19-targeted chimeric antigen receptor modified T-cell immunotherapy (CAR-T cell therapy) is a novel treatment with promising results in patients with relapsed/refractory lymphoid malignancies. CAR-T cell therapy has known early toxicities of cytokine release syndrome (CRS) and neurotoxicity, but little is known about long-term neuropsychiatric adverse effects. We have utilized patient-reported outcomes (PROs), including PROMIS® measures, to assess neuropsychiatric and other patient-reported outcomes of 40 patients with relapse/refractory chronic lymphocytic leukemia (CLL), non-Hodgkin lymphoma (NHL), and acute lymphoblastic leukemia (ALL), one to five years after treatment with CD19-targeted CAR-T cells. Mean T scores of PROMIS domains of Global Mental health, Global Physical Health, Social Function, anxiety, depression, fatigue, pain and sleep disturbance were not clinically meaningfully different from the mean in the general US population. However, 19 patients (47.5%) reported at least one cognitive difficulty and/or clinically meaningful depression and/or anxiety, and 7 patients (17.5%) scored ≤ 40 in Global Mental Health, indicating at least one standard deviation worse than the general population mean. Younger age was associated with worse long-term Global Mental Health (p=0.02), anxiety (p=0.001) and depression (p=0.01). Anxiety prior to CAR-T cell therapy was associated with increased likelihood of anxiety after CAR-T cell therapy (p=0.001). 15 patients (37.5%) reported cognitive difficulties post CAR-T cell therapy. Depression prior to CAR-T cell therapy was statistically significantly associated with higher likelihood of self-reported post CAR-T cognitive difficulties (p=0.02) and there was a trend for association between acute neurotoxicity and self-reported post-CAR-T cognitive difficulties (p=0.08). Having more post-CAR-T cognitive difficulties was associated with worse Global Mental Health and Global Physical Health. Our study demonstrates overall good neuropsychiatric outcomes in 40 long-term survivors after CAR-T cell therapy. However, nearly 50% of patients in the cohort reported at least one clinically meaningful negative neuropsychiatric outcome (anxiety, depression or cognitive difficulty), indicating that there is a significant number of patients who would likely benefit from mental health services following CAR-T cell therapy. Younger age, pre-CAR-T anxiety or depression, and acute neurotoxicity may be risk factors for long-term neuropsychiatric problems in this patient population. Larger studies are needed to confirm these findings.