1. HLH-like toxicities predict poor survival following use of tisagenlecleucel in children and young adults with B-ALL
- Author
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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, and Schultz, Liora M
- Subjects
Biomedical and Clinical Sciences ,Clinical Sciences ,Hematology ,Pediatric ,Rare Diseases ,Humans ,Child ,Young Adult ,Lymphohistiocytosis ,Hemophagocytic ,Retrospective Studies ,Receptors ,Antigen ,T-Cell ,Receptors ,Chimeric Antigen ,Precursor B-Cell Lymphoblastic Leukemia-Lymphoma ,Burkitt Lymphoma ,Chronic Disease ,Cardiovascular medicine and haematology - 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.
- Published
- 2023