Abstract
Abstracts From
JADPRO Live at APSHO 2017
Marriott Marquis, Houston, Texas • November 2–5, 2017
The posters for the abstracts below can be found at:
eventscribe.com/2017/posters/JADPROLIVE/home.asp
JL516. Management of Cytokine Release Syndrome and Neurologic Events in ZUMA-1: Anti-CD19 CAR T-Cell Therapy, Axicabtagene Ciloleucel (axi-cel), in Patients With Refractory, Aggressive Non-Hodgkin Lymphoma
Background: Chimeric antigen receptor (CAR) T-cell therapy is a promising treatment option for patients with refractory aggressive non-Hodgkin lymphoma (NHL). ZUMA-1, a pivotal, multicenter trial of axi-cel resulted in an objective response rate of 82% (54% complete responses; Locke et al., 2017). CAR T-cell therapy is associated with cytokine release syndrome (CRS) and neurologic events (NE). Advanced practitioners (APs) should be familiar with the clinical presentation and management of CAR T cell-associated AEs.
Methods: Eligible patients were leukapheresed and received low-dose conditioning chemotherapy followed by axi-cel administration as inpatients. Patients were monitored for at least 7 days post-infusion in the hospital. APs at sites reviewed cases to compare multicenter approaches and collate experiences into informative, best practices.
Results: Ninety-three percent of patients experienced CRS (13% grade ≥ 3) and 64% experienced NE (28% grade ≥ 3). Nearly all CRS and NE was reversible. Thorough and consistent physical, laboratory, and neurologic assessments from baseline to discharge allowed for early identification of symptoms. For CRS, pyrexia was a common early symptom (76%), followed by hypotension (41%), hypoxia (22%), and tachycardia (21%). Familiarity with standardized CRS grading by unit nurses enabled rapid escalation to APs in cases of CRS progression. Current axi-cel CRS management guidance (Lee et al., 2014) recommends continuous cardiac telemetry and pulse oximetry for patients with grade 2 CRS; and grade ≥ 3 CRS requires management in a monitored care or intensive care unit. Patients requiring vasopressors (13%) for hypotension required telemetry monitoring. If available, telemetry was monitored within the treatment unit to reduce transfer to the intensive care unit for telemetry alone. Daily monitoring for elevated C-reactive protein and ferritin levels may identify patients at greater risk for severe CRS and hemophagocytic lymphohistiocytosis. NE onset was generally later than that of CRS. For NE, handwriting impairment often preceded common symptoms of encephalopathy (34%), confusion (29%), and tremor (29%). Case reports will be presented illustrating real-world experiences managing patients treated with CAR T-cell therapy.
Summary: Axi-cel has demonstrated significant clinical benefit but with a distinct toxicity profile associated with this class of therapy. While toxicities could be severe, they were generally manageable and reversible.
Implications: Close patient monitoring by unit nurses and early AE interventions by APs was critical to optimizing safety. Collaboration between departments and across sites allows continued refinement of management strategies, further optimizing care and improving the benefit:risk ratio of CAR T-cell therapy.
