Cytokine profiling, pretreatment with anakinra, and tolerance development in platinum-induced mixed hypersensitivity reactions

Ann Allergy Asthma Immunol. 2023 Oct;131(4):501-512.e9. doi: 10.1016/j.anai.2023.06.011. Epub 2023 Jun 14.

Abstract

Background: Cytokine-release reactions (CRR) induced by platinum-based chemotherapy, manifesting with fever, chills, and rigors, are poorly understood and not easily prevented by usual premedication or desensitization.

Objective: To gain a better understanding of platinum-induced CRR and to explore the use of anakinra as a tool to prevent its clinical manifestations.

Methods: A cytokine and chemokine panel was obtained before and after platinum infusion in 3 cases with a mixed (immunoglobulin E-mediated and CRR) platinum-induced hypersensitivity reaction and in 5 controls either tolerant or with an immunoglobulin E-mediated platinum-induced hypersensitivity reaction. Anakinra was given as premedication in the 3 CRR cases.

Results: Cytokine-release reaction was associated with a marked release of interleukin (IL)-2, IL-5, IL-6, IL-10, and tumor necrosis factor-ɑ in all cases whereas only IL-2 and IL-10 increased in some controls after platinum infusion, and to a lesser extent than in cases. Anakinra seemed to block CRR symptoms in 2 cases. In the third case, who initially had CRR symptoms despite anakinra, tolerance to oxaliplatin appeared to develop after repeated re-exposures, as suggested by the decreasing levels of cytokines after oxaliplatin, except IL-10, and the capacity to progressively shorten the desensitization protocol and taper the premedication, in addition to the negativization of the oxaliplatin skin test result.

Conclusion: In patients with platinum-induced CRR, anakinra could be a useful premedication to block its clinical manifestations, and monitoring of IL-2, IL-5, IL-6, IL-10, and tumor necrosis factor-ɑ could help predict tolerance development, thereby allowing safe adjustments to the desensitization protocol and premedication.

MeSH terms

  • Antineoplastic Agents* / adverse effects
  • Cytokines
  • Drug Hypersensitivity* / drug therapy
  • Humans
  • Hypersensitivity* / drug therapy
  • Immunoglobulin E
  • Interleukin 1 Receptor Antagonist Protein / therapeutic use
  • Interleukin-10
  • Interleukin-2 / therapeutic use
  • Interleukin-5
  • Interleukin-6
  • Organoplatinum Compounds / adverse effects
  • Oxaliplatin / adverse effects
  • Platinum / therapeutic use
  • Tumor Necrosis Factor-alpha

Substances

  • Oxaliplatin
  • Antineoplastic Agents
  • Interleukin 1 Receptor Antagonist Protein
  • Platinum
  • Interleukin-2
  • Interleukin-10
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Interleukin-5
  • Organoplatinum Compounds
  • Cytokines
  • Immunoglobulin E