Obinutuzumab-associated Infusion-related Reactions May Be Due to Cytokine Release

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Cytokine release may be part of the pathophysiology of infusion-related reactions in patients with chronic lymphocytic leukemia.
Cytokine release may be part of the pathophysiology of infusion-related reactions in patients with chronic lymphocytic leukemia.

Cytokine release may be part of the pathophysiology of infusion-related reactions as a result of obinutuzumab administration in patients with chronic lymphocytic leukemia (CLL), according to a letter to the editor published online ahead of print in the journal Blood has shown.1

Infusion-related reactions commonly occur with rituximab administration, a type I anti-CD20 monoclonal antibody often used for the treatment of CLL.

The pathophysiology of the reactions has been attributed to cytokine release with patients experiencing infusion-related reactions found to release higher levels of IL-8, IL-6, and TNF-α than those who did not. Patients with baseline absolute lymphocyte count ≥50 x 109/L are at the greatest risk of developing a reaction.

Obinutuzumab, a type II anti-CD20 monoclonal antibody used for the treatment of CLL, has been associated with a greater incidence and severity of infusion-related reactions than with rituximab.

Therefore, researchers sought to evaluate whether the underlying pathophysiology of obinutuzumab-associated infusion-related reaction is similar to that of rituximab.

For the study, researchers analyzed data from 38 patients with CLL who participated in two phase 1/2 trials. All participants were treated with obinutuzumab monotherapy.

RELATED: Supplemental NDA Submitted to FDA for Ibrutinib in Treatment-Naïve CLL

Results showed that 92% of patients developed symptoms of infusion-related reaction with the first infusion. Three patients discontinued treatment permanently due to infusion-related reaction.

The researchers found that the first obinutuzumab administration triggered immediate and strong release of IL-6, IL-8, TNF-α, IFN-γ, and IL-10.

The findings suggest that intervention strategies targeting cytokines may be a potentially effective strategy to reduce the incidence and severity of infusion-related reactions caused by obinutuzumab.

Reference

  1. Freeman CL, Morschhauser F, Sehn L, et al. Cytokine release in patients with CLL treated with obinutuzumab and possible relationship with infusion related reactions [published online ahead of print October 7, 2015]. Blood. doi: 10.1182/blood-2015-09-670802.

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