Toxicity management for patients receiving novel T-cell engaging therapies

Curr Opin Pediatr. 2014 Feb;26(1):43-9. doi: 10.1097/MOP.0000000000000043.


Purpose of review: Recent clinical trials using T-cell engaging immunotherapies such as bispecific antibodies which target T cells and tumor cells, as well as engineered T cells that express targeting and activation molecules known as chimeric antigen receptors, have demonstrated powerful proof of concept. These therapies result in a significant degree of immune activation in the patient, which has correlated with greatly increased efficacy but also with notable toxicity. These therapies produce nonphysiologic T-cell activation, which is the hallmark of these new, highly active treatments.

Recent findings: We and others have noted cytokine activation profiles that correlate with both toxicity and efficacy in patients receiving T-cell engaging therapies. Effector cytokines such as interferon-γ are elevated, but so are cytokines that are associated with macrophage activation syndrome/hemophagocytic lymphohistiocytosis, such as interleukin (IL)-10 and IL-6. Although corticosteroids can control some of these toxicities, a targeted approach may produce superior toxicity control without interfering with efficacy. One approach we have developed targets IL-6, a key cytokine in the toxicity response, using the IL-6 receptor antagonist tocilizumab.

Summary: Detailed studies of the T-cell activation produced by these novel therapies has led to more targeted approaches that have the potential to control toxicity while maintaining efficacy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antibodies, Bispecific / adverse effects
  • Antigens, CD19 / immunology
  • Child
  • Cytokines / biosynthesis
  • Humans
  • Immune System Diseases / immunology
  • Immunotherapy / adverse effects*
  • Immunotherapy / methods
  • Lymphocyte Activation / immunology
  • Lymphohistiocytosis, Hemophagocytic / immunology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / immunology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy
  • Receptors, Antigen, T-Cell / immunology
  • Syndrome
  • T-Lymphocytes / immunology*


  • Antibodies, Bispecific
  • Antigens, CD19
  • Cytokines
  • Receptors, Antigen, T-Cell
  • blinatumomab