Impact of preexisting mental health disorders and psychiatric pharmacotherapy on hospital length of stay in immune effector cell therapy recipients

Abstract

Abstract Introduction Chimeric antigen receptor T-cell therapy (CAR-T) and bispecific T-cell engagers (BiTE) have revolutionized cancer treatment, but their administration is associated with increased healthcare resource utilization. While toxicities such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are well characterized, less is known about how psychiatric factors affect outcomes. Prior work (Gouni S. et al., Blood 2024) suggests that pre-existing mental health disorders (MHDs) may impact toxicity and hospital length of stay (LOS). This study aimed to evaluate the independent and combined effects of cellular therapy type, MHD, and psychiatric pharmacotherapy on LOS among patients receiving immune effector cell (IEC) therapies. Methods We conducted a retrospective review of all adults treated with IEC therapy at Dartmouth Cancer Center from 2020–2024. MHDs were defined as DSM-5 psychiatric diagnoses documented prior to IEC initiation. Variables were abstracted via chart review. Hospital LOS within 30 days of IEC initiation was recorded. A gamma regression with log link was used to examine the association between LOS and three predictors: therapy type (CAR-T vs. BiTE), presence of a pre-existing MHD, and receipt of psychiatric pharmacotherapy defined as at least 28 days prior to admission, throughout admission, and at least 28 days post admission. We also developed a grouped model combining MHD and pharmacotherapy status into a 4-level categorical variable to assess interactive effects. Results Eighty-four patients receiving CAR-T (n=45, 54%) or BiTE (n=39, 46%) therapy were included. Most patients were male (n=45, 54%) and had a median age of 65 years (range: 19-86) at IEC infusion. Axicabtagene ciloleucel was the most common cellular therapy product. Pre-existing MHDs were identified in 31 patients (37%). Among the 84 patients, 26 had insomnia, 23 had depression, 22 had anxiety, 2 had post-traumatic stress disorder, and 1 had bipolar disorder. A total of 34 patients (40%) received psychiatric pharmacotherapy. Regarding pharmacologic treatment, 18 received benzodiazepines, 12 selective serotonin reuptake inhibitors (SSRIs), 8 serotonin antagonist reuptake inhibitors (SARIs), 5 serotonin norepinephrine reuptake inhibitors (SNRIs), and 5 norepinephrine dopamine reuptake inhibitors (NDRIs). Less common classes included tricyclics, atypical tetracyclics, antipsychotics, mood stabilizers, and nonbenzodiazepine hypnotics. In total, 16 patients (19%) had MHDs without psychiatric pharmacotherapy, 19 (23%) had psychiatric pharmacotherapy without a formal MHD diagnosis, and 15 (18%) had both. Fourteen patients (17%) experienced prolonged hospital stays >30 days and 21 patients (26%) required intensive care. CRS occurred in 43 patients (52%) and ICANS in 27 patients (33%). In the main effects model, CAR-T (p<0.001) and the presence of a pre-existing MHD (p=0.02) were independently associated with prolonged LOS. The use of psychiatric pharmacotherapy (p=0.04) was associated with a shorter LOS. In the grouped model based on MHD and pharmacotherapy status, patients with MHDs not receiving pharmacotherapy had the longest estimated LOS. This group effect was statistically significant (p=0.02). No significant differences were observed between MHD and non-MHD patients in CRS or ICANS, response rates, or overall survival. Conclusion Pre-existing mental health disorders were associated with prolonged LOS among patients receiving CAR-T and BiTE. Patients receiving psychiatric pharmacotherapy had a LOS comparable to those without psychiatric comorbidity, suggesting a potential protective effect. These findings underscore the importance of psychiatric assessment and management in patients receiving IEC therapy. Future studies are needed to determine whether proactive mental health interventions can reduce hospitalization burden, minimize treatment-related complications, and optimize overall care delivery.