Preemptive mitigation of CD19 CAR T-cell cytokine release syndrome without attenuation of antileukemic efficacy

Abstract

Gardner et al report that early intervention with tocilizumab and steroids at the first signs of mild cytokine release syndrome (CRS) following CD19 chimeric antigen receptor (CAR) T-cell infusion for B-cell acute lymphocytic leukemia reduces the development of life-threatening severe CRS without having a negative impact on antileukemic effect.

Corticosteroids do not influence the efficacy and kinetics of CAR-T cells for B-cell acute lymphoblastic leukemia

“…The possibility of our results differing from previous observation could be: we used high-dose steroids for short term (average 4 days; 91.3% ≤ 7 days) whereas they used longer time (Davila ML et al mentioned 3 cases accepted 7-21 days of high-dose steroids 7 ). Very recently, two studies showed that early intervention with corticosteroids for CRS 16 or neurotoxicity 17 does not impact on the antitumor potency of CD19 CAR -T cells, which support our results, the potential mechanisms need to be further explored.…”

The earlier the better: timely mitigation of CRS

“…In this issue of Blood, Gardner et al demonstrate that early pharmacologic mitigation of cytokine release syndrome (CRS) can reduce the severity of this commonly encountered syndrome without diminishing responses to CD19 chimeric antigen receptor (CAR) T cells. 1 As the use of CD19 CAR T cells has transitioned from early trials to commercial use, the number of patients experiencing CRS is now estimated at .2000 in total. [2][3][4][5] Practitioners and patients alike often refer to the syndrome as a "necessary evil," because its symptoms coincide with expansion/activation of CAR T cells as they come into contact with CD19 1 targets.…”

“…The authors also showed that these lymphomas display distinct prognostic and morphologic features (see figure). 1 Previous GEP studies have defined 2 major molecular subtypes within the group of PTCL-NOS diseases. 2,3 One subtype was identified by the expression of GATA3 and its target genes and was designated as the PTCL-GATA3 subtype; the other was identified by the expression of T-box 21 (TBX21) and its target genes and was designated as the PTCL-TBX21 subtype.…”

Clinical course of COVID-19 in a liver transplant recipient on hemodialysis and response to tocilizumab therapy: A case report

“…14 However, this was a single-arm trial with some patients receiving other therapies, thus, further data are awaited regarding the efficacy of tocilizumab. With regard to another recognized use of tocilizumab for cytokine release syndrome (CRS) associated with the administration of chimeric antigen-receptor T cells for leukemia, Gardner et al reported that early preemptive administration of tocilizumab might abrogate progression from mild CRS to severe CRS 15.…”