학술논문
Optimal fludarabine lymphodepletion is associated with improved outcomes following CAR T-cell Therapy
Document Type
article
Author
Fabrizio, Vanessa A; Boelens, Jaap Jan; Mauguen, Audrey; Baggott, Christina; Prabhu, Snehit; Egeler, Emily; Mavroukakis, Sharon; Pacenta, Holly L; Phillips, Christine L; Rossoff, Jenna; Stefanski, Heather; Talano, Julie-An An; Moskop, Amy; Margossian, Steven P; Verneris, Michael R; Myers, Gary Doug; Karras, Nicole A; Brown, Patrick A; Qayed, Muna; Hermiston, Michelle L; Satwani, Prakash; Krupski, Christa; Keating, Amy K; Wilcox, Rachel; Rabik, Cara A; Chinnabhandar, Vasant; Kunicki, Michael; Goksenin, A Yasemin; Mackall, Crystal L; Laetsch, Theodore W; Schultz, Liora M; Curran, Kevin J
Source
Blood Advances. 6(7)
Subject
Language
Abstract
Chimeric antigen receptor (CAR) T cells provide a therapeutic option in hematologic malignancies. However, treatment failure after initial response approaches 50%. In allogeneic hematopoietic cell transplantation, optimal fludarabine exposure improves immune reconstitution, resulting in lower nonrelapse mortality and increased survival. We hypothesized that optimal fludarabine exposure in lymphodepleting chemotherapy before CAR T-cell therapy would improve outcomes. In a retrospective analysis of patients with relapsed/refractory B-cell acute lymphoblastic leukemia undergoing CAR T-cell (tisagenlecleucel) infusion after cyclophosphamide/fludarabine lymphodepleting chemotherapy, we estimated fludarabine exposure as area under the curve (AUC; mg × h/L) using a validated population pharmacokinetic (PK) model. Fludarabine exposure was related to overall survival (OS), cumulative incidence of relapse (CIR), and a composite end point (loss of B-cell aplasia [BCA] or relapse). Eligible patients (n = 152) had a median age of 12.5 years (range,