Longitudinal Patient-Reported Outcomes in Patients Receiving Chimeric Antigen Receptor (CAR) T-Cell Therapy

Abstract

Background: CAR T-cell therapy is a novel treatment for patients with hematologic malignancies that carries risk of unique toxicities such as cytokine release syndrome (CRS) and immune effector cell-associated neurologic toxicity (ICANS). Patients are at risk for quality of life (QOL) deterioration and immense physical and psychological symptom burden given these toxicities, their illness, and the need for a prolonged hospitalization. Yet, data that comprehensively depict the longitudinal patient-reported outcomes (PROs) of patients receiving CAR T-cell therapy are limited. Methods: We conducted a longitudinal cohort study of 100 consecutive adult patients with hematologic malignancies receiving CAR T-cell therapy at Massachusetts General Hospital (MGH) between 4/2019 and 11/2021. Patients completed baseline questionnaires prior to receipt of CAR T-cell therapy about sociodemographic data, QOL (Functional Assessment of Cancer Therapy-General), physical symptoms (Edmonton Symptom Assessment Survey-revised [ESAS-r]), and psychological distress (Hospital Anxiety and Depression Scale and Post-Traumatic Stress Checklist) and completed PRO questionnaires at 1 week, 1 month, 3 months, and 6 months after CAR T-cell infusion. We used descriptive statistics to summarize patient characteristics and PROs at each timepoint and rates of clinically significant depression, anxiety, and post-traumatic stress disorder (PTSD) based on establish cutoffs. We conducted paired t-tests analyzing changes in QOL, physical, and psychological symptoms from baseline to 1 week, 3 months, and 6 months. We used multivariable linear regression models to examine factors associated with QOL at three months after CAR T-cell infusion. Results: We enrolled 71.4% (100/140) of eligible patients (median age 66 years; 63% male sex; 77% married/living with partner). The most common diagnosis was lymphoma (71%) followed by multiple myeloma (28%); A plurality (34%) received tisagenlecleucel, followed by lisocabtagene maraleucel (16%), axicabtagene ciloleucel (13%), and idecabtagene vicleucel (12%). The overall response rate was 80%, and with a median follow up of 14 months after CAR T-cell infusion, 38% died. CRS and ICANS occurred in 76% and 33% of patients, respectively. At baseline, median QOL score was 77.9 (range: 34-107), and was 70.0 (35-107) at 1 week, 76.0 (46-106) at 1 month, 83.5 (29-108) at 3 months, and 83.7 (34-107) at 6 months. Severe physical symptoms (ESAS-r score >=7) were reported by 47%, 52%, 35%, 28%, and 28% of patients at baseline, 1 week, 1 month, 3 months, and 6 months, respectively. The rates of clinically significant anxiety, depression, and PTSD symptoms at each time point are depicted in figure 1. Patient's QOL decreased at 1 week (mean difference [md]=5.1, p=0.04), but increased at 3 months (md -5.2, p=0.04) and 6 months (md=-5.3, p=0.07) compared to baseline. Patient's physical symptoms increased at 1 week, but decreased at 3 months (md 5.1, p=0.03) and 6 months (md=4.5, p=0.07), compared to baseline. There was no significant difference in anxiety symptoms from baseline to 1 week, 1 month, or 3 months. Anxiety symptoms improved at 6 months compared to baseline. There was no significant difference in depression or PTSD symptoms across all time points compared to baseline. In univariate linear regression, older age (β=0.4; p=0.01) and undergraduate or graduate degree (β=7.53, p=0.04) were associated with better QOL, whereas baseline anxiety symptoms (β=-14.3, p<0.01), baseline depression symptoms (β=-16.6, p<0.01), and baseline PTSD symptoms (β=-18.8, p<0.01) were associated with worse QOL at 3 months. In separate multivariable models including age, sex, education, marital status, and Eastern Cooperative Oncology Group performance status given collinearity among baseline PROs, anxiety (β=-10.6, p<0.01), depression (β=-12.6, p<0.01), and PTSD symptoms (β=-16.2, p<0.01) were the only factors associated with QOL at 3 months. Conclusion: Patients receiving CAR T-cell therapy experience significant QOL impairment and physical and psychological symptom burden, which peaks 1 week after cell infusion and improves by 6 months post-infusion. Given high rates of persistent severe symptoms and clinically significant psychological distress, interventions to improve the QOL of these patients are warranted. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal