Patient-Reported Neuropsychiatric Outcomes of Long-Term Survivors after Chimeric Antigen Receptor T Cell Therapy. Biol Blood Marrow Transplant 2020 Jan;26(1):34-43
Date
10/13/2019Pubmed ID
31605820Pubmed Central ID
PMC6951812DOI
10.1016/j.bbmt.2019.09.037Scopus ID
2-s2.0-85075482768 (requires institutional sign-in at Scopus site) 141 CitationsAbstract
CD19-targeted chimeric antigen receptor (CAR) modified T cell immunotherapy 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 and neurotoxicity, but little is known about long-term neuropsychiatric adverse effects. We have used patient-reported outcomes, including Patient-Reported Outcomes Measurement Information System (PROMIS) measures, to assess neuropsychiatric and other patient-reported outcomes of 40 patients with relapse/refractory chronic lymphocytic leukemia, non-Hodgkin lymphoma, and acute lymphoblastic leukemia 1 to 5 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 1 cognitive difficulty and/or clinically meaningful depression and/or anxiety, and 7 patients (17.5%) scored ≤40 in global mental health, indicating at least 1 standard deviation worse than the general population mean. Younger age was associated with worse long-term global mental health (P = .02), anxiety (P = .001), and depression (P= .01). Anxiety before CAR T cell therapy was associated with increased likelihood of anxiety after CAR T cell therapy (P = .001). Fifteen patients (37.5%) reported cognitive difficulties after CAR T cell therapy. Depression before CAR T cell therapy was statistically significantly associated with higher likelihood of self-reported post-CAR T cognitive difficulties (P = .02), and there was a trend for an association between acute neurotoxicity and self-reported post-CAR T cognitive difficulties (P = .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 1 clinically meaningful negative neuropsychiatric outcome (anxiety, depression, or cognitive difficulty), indicating that a significant number of patients 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.
Author List
Ruark J, Mullane E, Cleary N, Cordeiro A, Bezerra ED, Wu V, Voutsinas J, Shaw BE, Flynn KE, Lee SJ, Turtle CJ, Maloney DG, Fann JR, Bar MAuthors
Kathryn Eve Flynn PhD Vice Chair, Professor in the Medicine department at Medical College of WisconsinBronwen E. Shaw MBChB, PhD Center Director, Professor in the Medicine department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
Adoptive TransferAdult
Aged
Female
Follow-Up Studies
Humans
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, Non-Hodgkin
Male
Middle Aged
Neurocognitive Disorders
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Self Report
