Successful Application of Tocilizumab in a Patient With Neoadjuvant Immunochemotherapy-Induced Cytokine Release Syndrome

Abstract

Background: The expansion of preoperative immunochemotherapy has led to an increase in the number of patients with lung cancer receiving immune checkpoint inhibitors (ICIs). Therefore, oncologists should manage a variety of immune-related adverse events (irAEs). One of the rare, life-threatening, and recently proposed irAEs is cytokine release syndrome (CRS). Although the standard treatment of irAE is systemic administration of steroids, it has been suggested that tocilizumab may be an effective treatment option for CRS.

Case: This case describes a 69-year-old man with stage IIIA lung adenocarcinoma who received chemotherapy and nivolumab, which is an ICI, as neoadjuvant immunochemotherapy. After the first administration, the patient developed severe skin rash, fever, and arthralgia. We suspected irAEs and administered systemic steroids. However, fever and arthralgia did not improve, although the skin rash disappeared. These were also significant challenges for surgery. Noting the elevated levels of inflammatory cytokines, we consulted a rheumatologist. Finally, we decided to terminate neoadjuvant therapy after one cycle and administer tocilizumab. Tocilizumab dramatically improved the patient's symptoms and allowed him to undergo radical surgery. Pathological findings revealed that the patient achieved a major pathological response.

Conclusion: This indicates the potential effectiveness of early tocilizumab administration for ICI-induced CRS, even in mild cases.

Keywords: adenocarcinoma; cytokine release syndrome; neoadjuvant therapy; nivolumab; tocilizumab.

FIGURE 1

Only one course of nivolumab and chemotherapy resulted in significant shrinkage of the tumor.

FIGURE 2

After the surgery, the residual tumor cells represented less than 5% of the primary lung lesion and were not detected in the lymph nodes.

FIGURE 3

A brief diagram of the patient. Twenty‐one days after the first cycle of immunochemotherapy, the patient developed grade 3 skin rash, grade 1 fever, and grade 1 arthralgia. Prednisolone treatment at a dosage of 60 mg (1 mg/kg body weight) was initiated. Although the skin rash had resolved, the patient still had slight fever, arthralgia, and anemia. After consultation with the rheumatologist, the patient was diagnosed with ICI‐induced CRS and treated with a subcutaneous injection of tocilizumab on days 64 and 72 after the first cycle of immunochemotherapy. With tocilizumab treatment, the patient's symptoms substantially improved. On day 85 after the first cycle of immunochemotherapy, he underwent radical surgery. CDDP, cisplatin; PEM, pemetrexed; PSL, prednisolone.