Dataset Information

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

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.

SUBMITTER: Ruark J

PROVIDER: S-EPMC6951812 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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

Ruark Julia J Mullane Erin E Cleary Nancy N Cordeiro Ana A Bezerra Evandro D ED Wu Vicky V Voutsinas Jenna J Shaw Bronwen E BE Flynn Kathryn E KE Lee Stephanie J SJ Turtle Cameron J CJ Maloney David G DG Fann Jesse R JR Bar Merav M

Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation 20191009 1

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 ...[more]

PMID: 31605820

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Project description:Patient-reported outcomes (PROs) are an important tool to assess the impact of a new therapy on symptom burden and health-related quality of life (HRQoL). Chimeric antigen receptor T (CAR-T) cell therapies have been approved for use in relapsed or refractory leukemia and lymphoma based on promising efficacy in clinical trials. However, data are lacking on patient-reported toxicity and impact on HRQoL. This review provides an overview of the incorporation of PROs in CAR-T cell therapy and the specific challenges in this context. The first step is to demonstrate feasibility of PRO monitoring in the acute phase after CAR-T cell infusion. Apart from core PRO domains like physical functioning, disease-related symptoms, and symptomatic adverse effects, important measures to consider are cognitive functioning and financial toxicity. Because there are no validated PRO instruments in the setting of CAR-T cell therapy, universally validated measures like Patient-Reported Outcomes Measurement Information System (PROMIS) could be considered, which is also recommended in the setting of hematopoietic stem cell transplantation. Given the timeline of toxicities with CAR-T cell therapy, PRO instruments should be administered at baseline and at least weekly in the first 30 days. Subsequently, frequent monitoring of PROs in the first year might be helpful in identifying short- and intermediate-term toxicities, functional limitations, and neuropsychiatric effects. The major potential challenge in acute phase would be missing data when patients develop severe cytokine release syndrome or neurotoxicity. Designing a strategy for handling missing data is crucial. The long-term safety of CAR-T cell therapy is not well characterized because of short follow-up in most studies reported thus far. PROs should be measured at least yearly after the first year to identify potential late effects like cognitive deficit or autoimmune manifestations. Collaboration between institutions performing cellular therapy and engagement with patients, clinicians, and statisticians with expertise in PROs are crucial for setting a comprehensive agenda on integration of PROs with CAR-T cell therapy.

Project description:BackgroundThe effect of surgeon factors on patient-reported quality-of-life outcomes after breast-conserving therapy (BCT) is unknown and may help patients make informed care decisions.MethodsWe performed a survey study of women aged ≥ 67 years with non-metastatic breast cancer diagnosed in 2009 and treated with guideline-concordant BCT, to determine the association of surgeon factors with patient-reported outcomes. The treating surgeon was identified using Medicare claims, and surgeon factors were identified via the American Medical Association Physician Masterfile. The primary outcome was patient-reported cosmetic satisfaction measured by the Cancer Surveillance and Outcomes Research Team (CanSORT) Satisfaction with Breast Cosmetic Outcome instrument, while secondary outcomes included BREAST-Q subdomains. All patient, treatment, and surgeon covariables were included in a saturated multivariable linear regression model with backward elimination applied until remaining variables were p < 0.1.ResultsOf 1650 women randomly selected to receive the questionnaire, 489 responded, of whom 289 underwent BCT. Median age at diagnosis was 72 years and the time from diagnosis to survey was 6 years. The mean adjusted CanSORT score was higher for patients treated by surgical oncologists than patients treated by non-surgical oncologists (4.01 [95% confidence interval [CI] 3.65-4.38] vs. 3.53 [95% CI 3.28-3.77], p = 0.006). Similarly, mean adjusted BREAST-Q Physical Well-Being (91.97 [95% CI 86.13-97.80] vs. 83.04 [95% CI 80.85-85.22], p = 0.006) and Adverse Radiation Effects (95.28 [95% CI 91.25-99.31] vs. 88.90 [95% CI 86.23-91.57], p = 0.004) scores were better among patients treated by surgical oncologists.ConclusionsSpecialized surgical oncology training is associated with improved long-term patient-reported outcomes. These findings underscore the value of specialized training and may be useful to patients choosing their care team.

Project description:PURPOSE:For older women with breast cancer, local therapy options may include lumpectomy plus whole-breast irradiation (Lump + WBI), lumpectomy plus brachytherapy (Lump + Brachy), lumpectomy alone (Lump alone), mastectomy without radiation therapy (Mast alone), and mastectomy plus radiation therapy (Mast + RT). We surveyed a population-based cohort of older breast cancer survivors to assess the association of local therapy with long-term quality-of-life outcomes. METHODS AND MATERIALS:We used nationally comprehensive Medicare claims to identify women aged ?67 years in whom nonmetastatic breast cancer was diagnosed in 2009, who were treated with 1 of the 5 aforementioned treatment options, and who were still alive in 2015. From this cohort, 1650 patients (330 patients per treatment) were randomly selected. A survey that included the CanSORT (Cancer Surveillance and Outcomes Research Team) Satisfaction with Breast Cosmetic Outcome, BREAST-Q, Decisional Regret Scale, and EQ-5D-3L was mailed to potential participants. We used multivariable linear regression to assess associations between local therapy and outcomes after adjusting for patient, disease, and treatment covariates. RESULTS:Among the 489 women who returned the surveys (30% response rate), the median age at diagnosis was 72 years (range, 67-87 years). The interval from diagnosis to survey completion was approximately 6 years for all patients. Compared with Lump + WBI (adjusted score, 3.40), the CanSORT cosmetic satisfaction scores were higher for Lump + Brachy (score, 3.77; P = .007) and Lump alone (score, 3.80; P = .04) and lower for Mast + RT (score, 3.01; P = .006). Similar trends were seen for BREAST-Q cosmetic satisfaction. BREAST-Q psychosocial, sexual, and physical well-being and EQ-5D-3L global health status tended to be better in patients treated with less irradiation and less surgery. BREAST-Q adverse radiation effects were worse for Lump + WBI compared with Lump + Brachy. Decisional regret regarding surgery and radiation therapy did not differ across groups. Compared with patients treated with Lump + WBI, patients treated with Lump + Brachy and Lump alone reported slightly higher rates of in-breast recurrence (excess risk of 5.8% and 6.4%, respectively; P = .01). CONCLUSIONS:In this nationally diverse cohort, less irradiation and less surgery were associated with better long-term quality-of-life outcomes. However, patient regret regarding surgery and radiation therapy was similar across all groups.

Dataset Information

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

Publications

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

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