학술논문
HLH-like toxicities predict poor survival following use of tisagenlecleucel in children and young adults with B-ALL
Document Type
article
Author
McNerney, Kevin Owen; Lim, Stephanie Si; Ishikawa, Kyle; Dreyzin, Alexandra; Vatsayan, Anant; Chen, John J; Baggott, Christina; Prabhu, Snehit; Pacenta, Holly L; Phillips, Christine L; Rossoff, Jenna; Stefanski, Heather E; Talano, Julie-An; Moskop, Amy; Verneris, Michael R; Myers, Doug; Karras, Nicole A; Brown, Patrick A; Bonifant, Challice L; Qayed, Muna; Hermiston, Michelle L; Satwani, Prakash; Krupski, Christa; Keating, Amy K; Baumeister, Susanne HC; Fabrizio, Vanessa A; Chinnabhandar, Vasant; Egeler, Emily; Mavroukakis, Sharon; Curran, Kevin J; Mackall, Crystal L; Laetsch, Theodore W; Schultz, Liora M
Source
Blood Advances. 7(12)
Subject
Language
Abstract
Chimeric antigen receptor-associated hemophagocytic lymphohistiocytosis (HLH)-like toxicities (LTs) involving hyperferritinemia, multiorgan dysfunction, coagulopathy, and/or hemophagocytosis are described as occurring in a subset of patients with cytokine release syndrome (CRS). Case series report poor outcomes for those with B-cell acute lymphoblastic leukemia (B-ALL) who develop HLH-LTs, although larger outcomes analyses of children and young adults (CAYAs) with B-ALL who develop these toxicities after the administration of commercially available tisagenlecleucel are not described. Using a multi-institutional database of 185 CAYAs with B-ALL, we conducted a retrospective cohort study including groups that developed HLH-LTs, high-grade (HG) CRS without HLH-LTs, or no to low-grade (NLG) CRS without HLH-LTs. Primary objectives included characterizing the incidence, outcomes, and preinfusion factors associated with HLH-LTs. Among 185 CAYAs infused with tisagenlecleucel, 26 (14.1%) met the criteria for HLH-LTs. One-year overall survival and relapse-free survival were 25.7% and 4.7%, respectively, in those with HLH-LTs compared with 80.1% and 57.6%, respectively, in those without. In multivariable analysis for death, meeting criteria for HLH-LTs carried a hazard ratio of 4.61 (95% confidence interval, 2.41-8.83), controlling for disease burden, age, and sex. Patients who developed HLH-LTs had higher pretisagenlecleucel disease burden, ferritin, and C-reactive protein levels and lower platelet and absolute neutrophil counts than patients with HG- or NLG-CRS without HLH-LTs. Overall, CAYAs with B-ALL who developed HLH-LTs after tisagenlecleucel experienced high rates of relapse and nonrelapse mortality, indicating the urgent need for further investigations into prevention and optimal management of patients who develop HLH-LTs after tisagenlecleucel.