Recently, the single-cell metric termed polyfunctional strength index (PSI™) by IsoCode chip computed from preinfusion anti-CD19 chimeric antigen receptor (CAR)-T cell products has demonstrated a significant association with clinical response and cytokine release syndrome (CRS) of cancer patient to the therapy after cell product infusion.
In this review we describe CRS and neurotoxicity in patients with B cell malignancies treated with CD19 CAR-T cells in pivotal trials, and also provide insight into potential mechanisms associated with these toxicities based on studies conducted in a phase 1/2 clinical trial at the Fred Hutchinson Cancer Research Center.
These data support the contention that early intervention with tocilizumab and/or corticosteroids in subjects with early signs of CRS is without negative impact on the antitumor potency of CD19 CAR T cells.
CD19-targeting chimeric antigen receptor (CAR)-T cell therapy has shown great efficacy in patients with relapsed/refractory non-Hodgkin lymphoma (NHL) but has been associated with serious adverse effects, such as cytokine release syndrome (CRS).
Although the IL-6R antagonist tocilizumab is approved for treatment of CRS, there is no approved treatment of neurotoxicity associated with CD19-targeted CAR-T (CART19) cell therapy.
Although CART19-induced complications have been gradually recognized, local cytokine-release syndrome (CRS) at particular parts of the body has not been extensively studied.
Thus, therapy with the new CD19-BBz(86) CAR T cells produces a potent and durable antilymphoma response without causing neurotoxicity or severe CRS, representing a safe and potent anti-CD19 CAR T cell therapy.
Blinatumomab, a monoclonal antibody targeting CD19, is associated with cytokine release syndrome (CRS) and neurotoxicity, both of which require prompt recognition and management primarily with corticosteroids.
Blinatumomab, a monoclonal antibody targeting CD19, is associated with cytokine release syndrome (CRS) and neurotoxicity, both of which require prompt recognition and management primarily with corticosteroids.
Although cytokine release syndrome (CRS) and neurotoxicity have emerged as predominant noninfectious complications of CD19 CAR T-cell therapy, infections associated with this treatment modality have not been well documented.
Clinical experience with the anti-CD19 CAR T cell therapy tisagenlecleucel at the University of Pennsylvania (Penn) was used to develop the Penn grading scale for CRS.
In this report of our presentation at the 2018 Second French International Symposium on CAR-T cells (CAR-T day), we describe the clinical presentations of CRS and neurotoxicity in a cohort of 133 adults treated with CD19 CAR-T cells at the Fred Hutchinson Cancer Research Center, and provide insights into the mechanisms contributing to these toxicities.
We have demonstrated, in a humanized mouse model, that the inducible caspase-9 (iC9) safety switch can eliminate CD19.CAR-Ts in a dose-dependent manner, allowing either a selective containment of CD19.CAR-T expansion in case of CRS or complete deletion on demand granting normal B cell reconstitution.
Chimeric antigen receptor (CAR) T-cell therapy targeting CD19 has demonstrated remarkable success in targeting B-cell malignancies but is often complicated by serious systemic toxicity in the form of cytokine release syndrome (CRS).
Trials with second generation CD19 chimeric antigen receptors (CAR) T-cells report unprecedented responses but are associated with risk of cytokine release syndrome (CRS).