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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2758-2771 |
| Number of pages | 14 |
| Journal | Blood Advances |
| Volume | 7 |
| Issue number | 12 |
| DOIs | |
| State | Published - Jun 2023 |
Funding
Research (C.L.M.) and the V Foundation (K.O.M). K.I. and J.J.C. are partially supported by a grant from the NIH (U54MD007601 [Ola HAWAII]). S.P. is partially supported by a grant from the Food and Drug Administration (grant number U01 FD004979/U01 FD005978), which supports the UCSF-Stanford Center of Excellence in Regulatory Sciences and Innovation. The authors acknowledge the following individuals for their roles in supporting the successful institution of this study with administrative support from Anika Dove and Daisy Torres and the clinical investigators, Eugenia H. Cho and Benjamin R. Oshrine participated in technical editing of the manuscript. The authors acknowledge the Stanford REDCap platform developed and operated by Stanford Medicine Research information technology team. The REDCap platform services at Stanford are subsidized by Stanford School of Medicine Research Office and the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health (NIH), through grant UL1 TR001085. This work was supported by a grant from the St. Baldrick’s/Stand Up 2 Cancer Pediatric Dream Team Translational Cancer Research (C.L.M.). Stand Up 2 Cancer is a program of the Entertainment Industry Foundation administered by the American Association for Cancer Research. C.L.M. is a member of the Parker Institute for Cancer Immunotherapy, which supports the Stanford University Cancer Immunotherapy Program. The work was also supported by the Virginia and D.K. Ludwig Fund for Cancer Research (C.L.M.) and the V Foundation (K.O.M). K.I. and J.J.C. are partially supported by a grant from the NIH (U54MD007601 [Ola HAWAII]). S.P. is partially supported by a grant from the Food and Drug Administration (grant number U01 FD004979/U01 FD005978), which supports the UCSF-Stanford Center of Excellence in Regulatory Sciences and Innovation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH, HHS, or Food and Drug Administration. The authors acknowledge the following individuals for their roles in supporting the successful institution of this study with administrative support from Anika Dove and Daisy Torres and the clinical investigators, Eugenia H. Cho and Benjamin R. Oshrine participated in technical editing of the manuscript. The authors acknowledge the Stanford REDCap platform developed and operated by Stanford Medicine Research information technology team. The REDCap platform services at Stanford are subsidized by Stanford School of Medicine Research Office and the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health (NIH), through grant UL1 TR001085. This work was supported by a grant from the St. Baldrick’s/ Stand Up 2 Cancer Pediatric Dream Team Translational Cancer Research (C.L.M.). Stand Up 2 Cancer is a program of the Entertainment Industry Foundation administered by the American Association for Cancer Research. C.L.M. is a member of the Parker Institute for Cancer Immunotherapy, which supports the Stanford University Cancer Immunotherapy Program. The work was also supported by the Virginia and D.K. Ludwig Fund for Cancer
ASJC Scopus subject areas
- Hematology
