Association between pre-existing mental health history and higher risk of mental health outcomes post-CAR-t therapy in patients with hematologic malignancies

Abstract

Abstract Background: Chimeric Antigen Receptor T-cell Therapy (CAR-T) has emerged as a revolutionary immunotherapy that utilizes genetically modified T cells to target and eliminate malignant cells. The patient journey for this therapy is arduous and may significantly impact the mental health of those undergoing treatment. The specific relationship between pre-existing mental health disorders and the development of mental health issues following CAR-T therapy remains understudied. Understanding this knowledge gap is particularly crucial given the intense and often prolonged nature of CAR-T therapy, which can involve extended hospital stays, adverse events, and the psychological burden of managing a life-threatening illness. This present analysis aims to evaluate whether pre-existing mental health disorders influence the development of mental health issues after CAR-T therapy in patients with hematologic malignancies utilizing real-world data (RWD). Methods: A retrospective, multicenter RWD analysis was conducted using the TriNetX database on 03th July 2025. Two cohorts who received CAR-T therapy for hematologic malignancies were analyzed: 1) Patients without pre-existing mental health disorders and 2) Patients with pre-existing mental health disorders. CAR-T therapies included tisagenlecleucel, brexucabtagene autoleucel, axicabtagene ciloleucel, lisocabtagene maraleucel, idecabtagene vicleucel, and ciltacabtagene autoleucel. We analyzed the demographic characteristics of both cohorts. Cox Proportional Hazards Model Analysis was used to assess the primary outcome, which was the risk of development of mental health disorders. Results: We identified 3,290 patients with hematologic malignancies whose data regarding mental health disorders in the 3 years prior to, and in the 3 years after CAR-T treatment were available. The patients' mean age at the time of CAR-T therapy for Cohorts 1 (without pre-existing mental health disorders) and 2 (pre-existing mental health disorders, specifically mood disorders, anxiety and stress-related disorders, and behavior syndromes) was 59.6±18.8 years and 57±18.5 years, respectively. 67.3% of patients were male in Cohort 1, whereas 52.9% of patients were male in Cohort 2. Patients in Cohort 1 had an 83.2% lower risk of developing mental health outcomes compared to Cohort 2 (p<0.0001). Patients in Cohort 2 had a 69.6% higher risk of developing mental health outcomes, specifically mood disorders, after CAR-T therapy (p=0.0138). Patients in Cohort 2 also had a 12.3% higher risk of developing mental health outcomes related to anxiety and stress-related disorders (p=0.0530). There was a notable trend for Cohort 2 patients to develop behavior syndromes with psychological disturbances and physical factors (20.8% increased risk, p=0.0530). Male patients had a 19.6% lower risk of developing mental health outcomes compared to females (p<0.0001). Age at the time of CAR-T therapy did not significantly affect the risk of developing mental health outcomes (p=0.5682). A limitation of this analysis is the lack of data regarding specific details of diagnoses and whether the mental health disorders reported after CAR-T therapy were attributed to new onset or exacerbation of an existing disorder. Conclusions: This analysis offers a unique perspective on the mental health trajectories of CAR-T therapy recipients, considering their pre-treatment mental health status. The findings indicate that individuals without prior mental health disorders exhibited a substantially lower risk of developing mental health issues following CAR-T therapy. In contrast, patients with pre-existing mental health comorbidities demonstrated a statistically significant increase in the incidence of mood disorders, anxiety, and behavioral syndromes post-treatment. This stark difference underscores the importance of considering pre-existing mental health conditions when planning and administering CAR-T therapy. We acknowledge the need for further analyses, ideally incorporating detailed patient-level data, to validate and expand upon these findings. Treating CAR-T therapy patients requires a multidisciplinary approach to provide comprehensive care that addresses both the physical and psychological needs of patients undergoing this complex treatment. As CAR-T therapy continues to evolve as a promising treatment for hematologic malignancies, integrating robust mental health support will be paramount in optimizing patient care and quality of life.