Impact of autonomic dysfunction on function, toxicity, and survival in patients with lymphoma treated with CART.

Abstract

e19010 Background: Autonomic dysfunction (AD) is a phenomenon that has been identified in subsets of patients (pts) treated with chimeric antigen receptor T-cell therapy (CART) for hematologic malignancies. AD manifests as parasympathetic dysfunction with hypotension and tachycardia, unique from cytokine release syndrome, and often requires pharmacologic support with midodrine and/or the discontinuation of antihypertensives. The impact of AD on survival in CART pts has not been well studied. Our objective was to investigate the relationship between the presence of AD on survival outcomes and other toxicities in pts with lymphoma treated with CART. Methods: This retrospective single-institution study included adult pts with aggressive B-cell lymphomas (B-NHL) who received autologous CD-19 directed CART between 2018-2024. AD was defined by the addition of midodrine and/or the permanent discontinuation of antihypertensives after CART. CART-associated toxicities such as cytokine release syndrome (CRS) and neurotoxicity (NT) were measured. Median progression-free survival (mPFS) and overall survival (mOS) were determined by Kaplan-Meier. Results: Our study included 174 pts. Sex, race, presence of primary refractory disease, double hit lymphoma status, elevated LDH at apheresis, and use of bridging therapy were similar between AD and non-AD cohorts. Pts with post-CART AD were younger (58 vs 62 yrs in AD vs non-AD; p=0.03) more likely to receive axi-cel (p=0.03) and experience a higher incidence of CRS (p=0.047) and NT (p=0.01). Grade of CRS and NT were similar between AD and non-AD pts. AD pts had longer lasting CRS and required tocilizumab more often (p=0.01). Despite being younger, AD pts were twice as likely to be discharged with home physical therapy (p=0.05) and three times as likely to be discharged to a rehabilitation facility (p=0.01). Median follow-up for surviving pts was 18 months. Median PFS and OS were not different between AD and non-AD groups. However, mOS was significantly lower among pts who required midodrine (without changes to antihypertensives), as a marker of AD (p=0.01). Conclusions: The presence of AD in pts with B-NHL was associated with a higher incidence of CART toxicities including CRS and NT and a higher likelihood to require physical rehabilitation to improve functional outcomes post CART. The need for midodrine to manage AD post-CART was associated with decreased OS in B-NHL. Our findings support the consideration of AD as a predictor of functional, toxicity, and survival outcomes and should guide supportive care in the post-CART setting.