Elevated Eosinophil Count Following Pembrolizumab Treatment for Non-Small Cell Lung Cancer

Abstract

Immune-related adverse events (IRAEs) are a common yet problematic phenomenon in patients who are treated with immune checkpoint inhibitors (ICIs). Current research efforts have explored the exact pathophysiology of IRAEs in the clinical setting. However, a rare subset of IRAEs that is less highlighted and may cause detrimental effects are hematological IRAEs (heme-IRAEs). Of note, immune-induced eosinophilia itself is a heme-IRAE that is worthy of further investigation. In this report, we present two cases of advanced staged non-small cell lung cancer (NSCLC) treated with single-agent pembrolizumab, and who subsequently sustained markedly elevated eosinophil counts (EEC) on laboratory findings. The two patients were Caucasian and both were diagnosed with NSCLC, although with differing histologies: a 76-year-old male with adenocarcinoma and a 66-year-old female with squamous cell carcinoma. Programmed death-ligand 1 (PD-L1) expression was detected via immunohistochemistry (IHC) and molecular tumor profiling did not show any actionable oncogenic mutations. Both patients were treatment-naïve and received pembrolizumab as first-line systemic therapy. The male patient, a former heavy smoker, underwent 18 months of pembrolizumab treatment before high eosinophil counts and was diagnosed with immunotherapy-related apoptotic colopathy after colonoscopy. Following pembrolizumab discontinuation, he remains under surveillance with good disease control and does not show any ongoing symptoms. The female patient, a never-smoker, underwent 15 cycles of pembrolizumab before the discontinuation of the treatment after consistently high levels of eosinophil counts. Both patients were treated with systemic corticosteroids after the discontinuation of immunotherapy, and their eosinophil levels returned to normal values. However, the female patient declined any further therapy and expired 24 months after the discontinuation of immunotherapy. Immune-induced eosinophilia is a rare event and reported in only 2.9% of NSCLC cases. Outcomes in the two patients differed, indicating that further research related to eosinophilia and its causes in the context of varying histologies and clinical profiles of patients is warranted.

Keywords: (pd-l1); heme-related iraes; immune markers; immune-checkpoint inhibitors; metastatic non-small cell lung cancer.

Figure 1. Diagnostic images and the absolute eosinophil count for patient A while on pembrolizumab

A. PET demonstrating hypermetabolic activity at the pleural lining of the right lung base and a pulmonary nodule at the left lung base prior to pembrolizumab, the treatment response to pembrolizumab after discontinuing therapy, and the significant pneumonitis in the posterior left lower lobe from XRT and its partial resolution. B. Patient A absolute eosinophil and white blood cell count during pembrolizumab therapy displaying elevated counts at C4 and C5. The red line indicates the upper threshold of normal for eosinophil count PET: positron emission tomography; P: cycle at the previous institution; C: cycle; D: lab draw after discontinuation

Figure 2. Patient A colonoscopy imaging of the appendiceal orifice

(A) ileocecal valve cecum (B) and rectum (C) were normal upon visual examination. Endoscopic diagnoses confirmed no evidence of colitis, obvious large polyps, masses, or cancer

Figure 3. Diagnostic images and the absolute eosinophil count for patient B while on pembrolizumab

A. CT demonstrating right hilar lymph node lymphadenopathy (arrow) at diagnosis and progression within the right hilar lymph node and development and progression of a segment 7 liver metastasis during pembrolizumab treatment. B. Patient B absolute eosinophil and white blood cell counts during pembrolizumab therapy displaying elevated counts at C2, C13, C14, and C15. The red line indicates the upper threshold of normal for eosinophil count CT: computed tomography; C: cycle; D: lab draw after discontinuation