Impact of Neurotoxicity and Steroid Therapy on Cancer Progression-Free Survival in Lymphoma Patients Treated with anti-CD19 CAR T-cells

Abstract Background Immune effector cell-associated neurotoxicity syndrome (ICANS) is a frequent complication of CAR T-cell therapy. Most patients achieve complete symptom resolution without long-term neurological sequelae, yet the impact of ICANS and steroid therapy on oncological outcomes remains inadequately explored. We investigated the association between ICANS and steroid therapy with progression-free survival (PFS). Methods We included large B-cell lymphoma patients treated with anti-CD19 CAR T-cells. The primary outcome was 90-day PFS. The secondary outcomes included PFS, complete response, and overall survival (OS) at 30-day, 90-day, 180-day, and 365-day. The association between outcomes and ICANS and steroid treatment was assessed using logistic regression analyses adjusted for baseline factors. Results Overall, 241 patients were included. The median age was 60 years (IQR=51-66), 81 (33.6%) were females, 67 (27.8%) developed ICANS, and 142 (58.9%) achieved 90-day PFS. There was no association between ICANS development (adjusted odds ratio [aOR] 1.39 [95%CI=0.75-2.61]), maximum grade (aOR 1.24 [0.97-1.59]), duration (aOR 1.00 [95%CI=0.95-1.05] per 1-day increase), or day of onset (aOR 0.98 [95%CI=0.86-1.11] per 1-day increase) and 90-day PFS. There was no association between steroid therapy (aOR 1.25 [95%CI=0.73-2.14]) or cumulative dose (aOR 1.00 [95%CI=0.98-1.01] per 100-mg increase) and 90-day PFS. Similar results were observed for secondary outcomes, except for an association between ICANS and OS at 30-day (aOR 0.05 [95%CI=0.01-0.54]) and 90-day (aOR 0.35 [95%CI=0.15-0.80]), Conclusions Our findings suggest that ICANS and steroid therapy do not adversely impact the PFS in lymphoma patients receiving anti-CD19 CAR T-cells. Yet, ICANS might be associated with reduced early overall survival.