Pembrolizumab Induced Grade 4 Skin irAEs with Non-Small Cell Lung Cancer: Case Report and Review of Literature

Case Report

Ann Hematol Oncol. 2021; 8(12): 1381.

Pembrolizumab Induced Grade 4 Skin irAEs with Non-Small Cell Lung Cancer: Case Report and Review of Literature

Pengyu Zhou1,2, Jing Zhang2, Zhaohua Tan2, Jianbing Tang2, Bin Li2, Haiqin Peng2, Jing Zhang2, Rongrong Zhou2* and Chuanyi Zhou1*

1Department of Oncology, Yueyang People’s Hospital, Yueyang, PR China

2Department of Oncology, Xiangya Hospital, Central South University, Changsha, PR China

*Corresponding author: Rongrong Zhou, Department of Oncology, Xiangya Hospital, Central South University, Changsha, PR China

Chuanyi Zhou, Department of Oncology, Yueyang People’s Hospital, Yueyang, PR China

Received: August 24, 2021; Accepted: October 30, 2021; Published: November 06, 2021


Objectives: Immune Checkpoint Inhibitors (ICIs), including pembrolizumab, have exhibited substantial benefits in the treatment of several types of cancers. However, treatment with ICIs is often accompanied by immune-related adverse events (irAEs), we report a rare case of pembrolizumab induced grade 4 skin irAEs with non-small cell lung cancer (NSCLC).

Materials and Methods: We report about an advanced NSCLC patient with 4 grade skin irAEs, after the treatment of pembrolizumab. We also compared statistical laboratory results and imageological examinations to discuss the relative factors of the patient’s curative effect and adverse reactions.

Results and Conclusion: This case is the first report of a 4-degree skin reaction with the pembrolizumab in patients with NSCLC, and the patient has the characteristics of good curative effect and severe adverse reactions. The patient experienced grade 4 skin irAEs after five cycles of pembrolizumab. Increased eosinophil levels are associated with increased skin irAEs in patients. However, CEA and Cytokeratin 19 fragment changes did not show a significant correlation with their skin irAEs and efficacy. The study of this case can provide some reference for efficacy evaluation and treatment after severe skin irAEs in patients with NSCLC.

Keywords: Non-small-cell lung cancer; Pembrolizumab; Immune-related adverse event; Grade 4 skin irAEs


At present, many clinical trials have confirmed that checkpoint inhibitors (ICPI) are a broad-spectrum, effective, long-lasting, and relatively safe anti-tumor drug [1]. It suppresses and kills tumor cells by enhancing the body’s anti-tumor immune function, and has shown significant clinical efficacy in the treatment of a variety of malignant tumors. Among them, anti-programmed cell death protein 1 (PD-1) and its ligand (PD-1 ligand, PD-L1) can block the binding of PD-1 and PD-L1, and block negative regulatory signals. To restore T cell activity. Therefore, it can enhance the immune response, recognize and kill tumor tissue, and thus achieve the role of anti-tumor therapy [2, 3]. PD-1 and PD-L1 antibodies have changed the treatment of Non-Small Cell Lung Cancer (NSCLC) [4]. Anti-PD1 antibody enhancing the immune responses against carcinoma by blocking immune escape from PD-1 [5]. Pembrolizumab is a PD-1 inhibitor that approved for metastatic melanoma therapy in September 2014 and for second line treatment of NSCLC with tumors expressing PDL1 in October 2015 [6,7]. The US FDA approved pembrolizumab as a first line therapy for metastatic NSCLC in October 2016 [8]. Increasing use of ICPI has appeared a discrete group of immune-related adverse reactions (irAEs) [9]. Various irAEs have been reported in patients with advanced melanoma after anti-PD1 antibodies therapy [10,11], but little is known about various skin irAEs associated with anti-PD1 therapy in patients with NSCLC [12]. We present a case about grade 4 Skin irAEs encountered in our hospital. It is hoped to play a role in the treatment of related skin adverse events in patients with NSCLC after anti-PD1 antibody treatment.

Case Presentation

In a 69-year-old male with right lung adenocarcinoma and a history of smoking, computerized tomography (CT) in October 2018 showed that lymph nodes near the right upper trachea and right hilum were enlarged (Figure 3). He was diagnosed with right lung adenocarcinoma (T2bN2M0 stage IIIA TMB-H, MSS, PD-1: 100%) by tracheoscopic fibroscope biopsy and received pembrolizumab (100mg every 3 weeks) as therapy.

The patient developed red erythema on the left lower limb after two doses of pembrolizumab; it was not painful and did not itch, and was not treated. CT scans in December 2018 clearly indicated that the enlarged lymph nodes near the right upper trachea and right hilum were smaller than in October 2018. The treatment assessment was partial response (PR), close to complete response (CR) (Figure 3). The patient continued to receive treatment with pembrolizumab. The skin area of the patient’s rash expanded to the lower extremity knee joint after three doses of pembrolizumab. Due to his short stay in our hospital, the patient was treated with traditional Chinese medicine and ointment at a local hospital, and the skin symptoms were not significantly relieved.

After five doses of pembrolizumab, the patient developed red, painful, pruritic erythema on the limbs and torso, with discoloration around the erythema (Figure 1a). Admission laboratory data indicated elevated eosinophils (1*109/L) and a negative skin fungal test. Histopathology showed irregular hypertrophy of the spinous layer, with infiltration of lymphocytes and eosinophils around the superficial dermis consistent with allergic lesions (Figure 2a and 2b). CT in June 2019 confirmed that the cancer had not progressed (Figure 3). According to these composite findings, a diagnosis of grade 4 skin immune-related adverse events (irAEs) was established. Pembrolizumab was discontinued, and the patient was treated with intravenous methylprednisolone for 3 days. At the same time, compound glycyrrhizin (80mg qd) was administered intravenously, levocetirizine (5mg qd) and bepotastine (10mg bid) were administered orally, and the itchy skin area was treated with mometasone cream. The area of epidermal desquamation was treated with urea cream. After 3 days of continuous treatment, the patient’s rash almost completely subsided, although pigmentation remained (Figure 1b). The patient’s rash and symptoms were significantly relieved and he was discharged.