Incidence and Management of Effusions during CD19-Directed Chimeric Antigen Receptor (CAR) T-Cell Receptor Therapy in B-Cell Lymphoma: A Single Institution Experience

Abstract

<h3>Background</h3> In patients with lymphoma, third space fluid accumulations may develop or worsen during cytokine release syndrome (CRS) associated with chimeric antigen receptor (CAR) T-cell therapy. Pre-existing symptomatic pleural effusions were excluded by the ZUMA-1 trial of axicabtagene ciloleucel (axi-cel) for large B cell lymphoma (LBCL) and variants. The optimal management of effusions that develop before or after axi-cel infusion in LBCL is unknown. <h3>Methods</h3> We performed a single center retrospective study evaluating 148 patients receiving CD19 CAR T-cell therapy for LBCL between 05/2015 and 09/2019. We identified all patients who developed pleural, pericardial and peritoneal effusions before (pre-CAR-T) or during the first 30 days after CAR T-cell infusion (post-CAR-T). Clinically relevant effusions were considered symptomatic based upon physician documentation. <h3>Results</h3> Total effusions and symptomatic effusions were noted in 24% (36/148) and 18% (27/148) of patients, respectively. Among 27 patients with symptomatic effusions, 59% (16/27) were pre-CAR-T effusions, 52% (14/27) persisted after day 30, and 44% (12/27) were malignant effusions. Overall, 67% of symptomatic effusions (18/27) were managed with diuretics, 44% (12/27) with a therapeutic thoracentesis or paracentesis and 33% (9/27) were observed with only supplemental oxygen provided. Six patients required pleural or abdominal catheters with a median indwelling duration of 54 (range, 29, 202) days, although 2 of these patients passed away with these indwelling catheters. Among symptomatic effusions developing only post-CAR-T (n=11), time to onset of effusion was median of 5 (range, 2-11) days and none of these patients required interventional drainage. Table 1 differentiates between effusions based on whether they were present (n = 19) or not (n = 17) prior to CAR T cell infusion. <h3>Conclusions</h3> Nearly half of all effusions diagnosed in patients receiving CAR T cell therapy develop after infusion but most can be medically managed. Patients with pre-CAR-T effusions may require procedural drainage or indwelling catheters, as these effusions may persist beyond the acute CRS period.