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HLH-like toxicities predict poor survival following use of tisagenlecleucel in children and young adults with B-ALL

  • 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
  • And 13 more
Publication Date
Jun 27, 2023
eScholarship - University of California
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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.

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