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Biol Blood Marrow Transplant. 2020 Jan;26(1):34-43. doi: 10.1016/j.bbmt.2019.09.037. Epub 2019 Oct 9.

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

Author information

1
Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, Washington.
2
Clinical Research division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
3
Clinical Research division, Fred Hutchinson Cancer Research Center, Seattle, Washington; Public Health division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
4
Immunotherapy Integrated Research Center, Fred Hutchinson Cancer Research Center, Seattle, Washington.
5
Department of Medicine, University of Washington, Seattle, Washington.
6
Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin.
7
Clinical Research division, Fred Hutchinson Cancer Research Center, Seattle, Washington; Immunotherapy Integrated Research Center, Fred Hutchinson Cancer Research Center, Seattle, Washington.
8
Clinical Research division, Fred Hutchinson Cancer Research Center, Seattle, Washington; Immunotherapy Integrated Research Center, Fred Hutchinson Cancer Research Center, Seattle, Washington; Centro Paulista de Oncologia, Sao Paulo, Brazil.
9
Clinical Research division, Fred Hutchinson Cancer Research Center, Seattle, Washington; Immunotherapy Integrated Research Center, Fred Hutchinson Cancer Research Center, Seattle, Washington. Electronic address: mbar@fredhutch.org.

Abstract

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.

KEYWORDS:

CD19-targeted CAR T cells; Late events; Patient-reported outcomes

PMID:
31605820
PMCID:
PMC6951812
[Available on 2021-01-01]
DOI:
10.1016/j.bbmt.2019.09.037

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