Impact of Neurological and Psychiatric Comorbidities on Toxicity and Outcomes of Patients with DLBCL Who Receive Axicabtagene Ciloleucel

• Published in: Blood 2024-11, Vol.144, p.7734-7734
• Main Authors: Albuquerque, Rebecca, Shamis, Anna, Tsalatsanis, Athanasios, Kumar, Ambuj, Ahmad, Zain, Ovais, Hasiq, Lazaryan, Aleksandr, Khimani, Farhad, Faramand, Rawan, Freeman, Ciara Louise, Shah, Bijal D, Gaballa, Sameh, Chavez, Julio C., Perna, Fabiana, Ochoa-Bayona, Jose L., Locke, Frederick L., Jain, Michael D., Nishihori, Taiga, Mirza, Abu-Sayeef
• Format: Article
• Language: English
• ISSN: 0006-4971
• DOI: 10.1182/blood-2024-208905

Introduction: Axicabtagene ciloleucel (axi-cel) is a CD-19-directed chimeric antigen therapy (CAR) T-cell therapy that has demonstrated efficacy in several malignancies including relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). However, cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) remain significant treatment related adverse events. In particular, the predictors of ICANS remain elusive. We hypothesized that neurological or psychiatric comorbidities may impact post-CAR-T toxicities and outcomes. Methods: We conducted a retrospective study of patients with R/R DLBCL who received commercial axi-cel at Moffitt Cancer Center in 2015-2023. Information on clinically significant pre-existing neurological and psychiatric comorbidities requiring medical management prior to axi-cel infusion were captured. Neurological comorbidities included cerebrovascular disease, demyelinating disorder, migraine, neurological infection, epileptic disorder, neurological neoplasms, neuromuscular disorder, and neuropathy. Psychiatric comorbidities included neurodevelopmental disorder, psychotic disorder, mood disorder, anxiety disorder, neurocognitive disorder, and insomnia. Cumulative incidences of toxicities were calculated for patients with and without comorbidities. Cox proportional hazards model and Kaplan Meier estimates were used to study survival post-CAR-T cell therapy. Results: From 279 patients with R/R DLBCL, the median age was 65 years (range: 20-86 years) and 61% were men. Nearly 50% of patients (139/279) had neurological comorbidities and 35% of patients (98/279) had psychiatric comorbidities. Incidence of any grade CRS for patients with neurological comorbidities was 86%, with 6% experiencing grade 3-5 CRS compared to patients without neurological comorbidities with an incidence of 93% any grade CRS with 4% experiencing grade 3-5 CRS. Incidence of any grade ICANS for patients with neurological comorbidities was 60%, with 25% experiencing grade 3-5 ICANS, compared to patients without neurological comorbidities had an incidence of any grade ICANS of 56%, with 22% patients experiencing severe ICANS. Median duration of ICANS was 5 (range: 1-92) days compared to 3 (range: 1-59) days for patients with and without neurological comorbidities, respectively (p=0.27). Having a history of neurological comorbidity did not predict for development of CRS (p=0.07) or ICANS (p=0.45). Incidence of all grades of CRS fo