Managing Cytokine Release Syndrome Associated With Novel T Cell-Engaging Therapies

By S. Maude, D. Barrett, D. Teachey, S. Grupp. Cancer Journal, 2014

704 citations recorded by the source corpus.

AbstractChimeric antigen receptor (CAR)-modified T cells and bispecific T cell–engaging antibodies have demonstrated dramatic clinical responses in recent clinical trials. The hallmark of these novel highly active immunotherapies is nonphysiologic T cell activation, which has correlated not only with greatly increased efficacy but also with notable toxicity in some cases. We and others have observed a cytokine release syndrome (CRS), which correlates with both toxicity and efficacy in patients receiving T cell–engaging therapies. In addition to elevations in effector cytokines, such as interferon-&ggr;, cytokines associated with hemophagocytic lymphohistiocytosis or macrophage activation syndrome, such as interleukin (IL)-10 and IL-6, may also be markedly elevated. Whereas corticosteroids may control some of these toxicities, their potential to block T cell activation and abrogate clinical benefit is a concern. Detailed studies of T cell proliferation and the resultant immune activation produced by these novel therapies have led to more targeted approaches that have the potential to provide superior toxicity control without compromising efficacy. One approach we have developed targets IL-6, a prominent cytokine in CRS, using the IL-6R antagonist tocilizumab. We will review the pathophysiology and management options for CRS associated with T cell–engaging therapies.

Subfields: Hematology, Immunology, Oncology

View Paper: https://www.semanticscholar.org/paper/086e40f48b5a0b2ad09aa18b2bddfa5bf68c2f5f

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Immunology

1. S. Evers
2. P. Hegde
3. V. Karanikas

In Oncology

1. S. Grupp
2. S. Maude
3. D. Teachey
4. D. Porter
5. S. Evers
6. P. Hegde
7. V. Karanikas
8. J. Kochenderfer

Citations in the corpus

• CD19-targeted chimeric antigen receptor T-cell therapy for acute lymphoblastic leukemia. (2015, background): “C-reactive protein (CRP) has been proposed as an indicator of severe CRS;(25) however, while high CRP correlates with severity of CRS in several studies, its use as a predictive biomarker is still being assessed.(26,73) We are currently determining if cytokine levels may be better predictors of CRS ”
• The Where, the When, and the How of Immune Monitoring for Cancer Immunotherapies in the Era of Checkpoint Inhibition (2016, background): “Early blood sampling is particularly important when acute toxicity is expected, such as the cytokine increase that is the hallmark of the cytokine release syndrome, the most common toxicity associated with T-cell engaging therapies such as chimeric antigen receptor (CAR)-modified T cells (68).”
• Universal Chimeric Antigen Receptors for Multiplexed and Logical Control of T Cell Responses (2018, neutral): “As many patients treated with CAR T cell therapy face cytokine release syndrome, which can be life threatening (Maude et al., 2014b; Morgan et al., 2010), it is important to prevent CAR T cell activity when necessary.”