Refractory cytokine release reaction to Nivolumab: Following desensitization algorithms to optimize the management of drug hypersensitivity

Abstract

Introduction Nivolumab is a fully human IgG4 monoclonal antibody (moAb) against programmed cell death protein 1, approved for the treatment of over ten types of cancer. The use of this and other moAbs has augmented considerably in recent years and this in turn has caused an increase of hypersensitivity reactions (HSR). Case report We present the case of a patient with metastatic renal cell cancer (RCC) who developed a grade 3 cytokine release reaction (CRR) to nivolumab. The maintenance of the symptoms despite of the administration of symptomatic treatment and slowing down the infusion rate of nivolumab during the 1st and 2nd reaction required an allergy evaluation of our patient. Management and outcome Skin testing to Nivolumab with negative results and baseline tryptase within the normal range were observed during the allergy workout. A desensitization protocol with specific premedication was applied to reintroduce the moAb, with no further issues. Moreover, a follow up of the patient in the oncology setting was done showing disease stabilization. Discussion The CRR should be treated by desensitization, in contrast to infusion reactions. The diagnosis of CRR phenotype is based on the clinical presentation and recently, and elevation of IL-6 levels has been shown to be a useful biomarker along with negative skin testing. We can conclude that after a HSR and an appropriate allergy diagnosis of CRR, nivolumab can be safely reintroduced by desensitization without reducing the target dose or the appropriate dilution concentration.

Nivolumab Hypersensitivity Reactions a Myth or Reality in Solid Tumors—A Systematic Review of the Literature

“…Only two cases in our research of the literature continued desensitization to Nivolumab as an alternative to continuing therapy: a 57 years old female with kidney cancer who developed an infusion reaction to Nivolumab during her third cycle and another patient with kidney cancer [ 22 , 31 ]. In one of the 19 cases Nivolumab was switched with Pembrolizumab and in another one, the combination of Vemurafenib and Cobimetinib was changed to Trametinib and Dabrafenib.…”

“…In our literature research, 10.53% of the patients (2/19 patients) died of the complications of the hypersensitivity reactions and 15.79% of the patients (3/19 patients) presented progression to disease and died afterward [ 17 , 19 , 23 , 25 , 26 ]. Only 5.26% of the patients (1/19 patients) had a complete response to Nivolumab treatment after DRESS and 15.79% of the patients (3/19 patients) had stable disease [ 9 , 22 , 28 , 31 ].…”