Advanced anaplastic thyroid carcinoma with positive expression of PD-L1 response to immune checkpoint inhibitors: A case report

Abstract

Anaplastic thyroid carcinoma (ATC) is one rare type of thyroid carcinoma without standard systemic treatment for advanced disease. Recent evidence has demonstrated promising efficacy of immune checkpoint inhibitors, particularly those targeting programmed death-1 (PD-1)/programmed death ligand 1 (PD-L1), in a variety of solid tumors. However, there have been no research of immune checkpoint inhibitors plus chemotherapy in ATC. Here, we present the case of a 37-year-old man with metastatic ATC with positive PD-L1 expression, who achieved long-term remission of 34 months after later-line treatment with zimberelimab (a PD-1 inhibitor) and nab-paclitaxel, followed by single-agent zimberelimab maintenance therapy. After three cycles of the combination treatment, the thyroid lesion and the liver metastases shrank dramatically, leading to the best overall response of partial remission. PD-L1 expression may serve as a potential biomarker for tumor response to immune checkpoint inhibitors in ATC. Our review highlights the need for further studies investigating the role of PD-L1 status as biomarker to predict the prognosis of immunotherapy in the treatment of ATC.

Keywords: Case report; PD-1/L1; anaplastic thyroid carcinoma; immune checkpoint inhibitor; immunotherapy biomarker; zimberelimab.

Figure 1.

Entire treatment process of the patient with poorly differentiated thyroid cancer.

Figure 2.

Pathologic diagnosis of poorly differentiated thyroid squamous cell carcinoma. (a, b) Hematoxylin and eosin staining (magnifications 200× and 400×); (c–h) immunohistochemistry staining: CK5/6 (magnifications 200× and 400×); P40 (magnifications 200× and 400×); P63 (magnifications 200× and 400×). CK5/6: cytokeratin5&6.

Figure 3.

The TPS of PD-L1 immunohistochemical staining (200×) from the patient. TPS: tumor proportion score; PD-L1: programmed death ligand 1.

Figure 4.

CT imaging of thyroid (a–e) and liver metastases (f–j) before and after zimberelimab plus nab-paclitaxel in the patient with ATC; arrows: the thyroid lesion and liver metastases. (a) Thyroid lesion before the first-line chemotherapy (tumor size: 5.2 × 7.1 cm). (b) Thyroid lesion after three cycles of gemcitabine+S-1 and one cycle of S-1 (tumor size: 3.4 × 1.9 cm). (c) Thyroid lesion before zimberelimab plus nab-paclitaxel (tumor size: 3.3 × 1.9 cm). (d) Thyroid lesion after three cycles of zimberelimab plus nab-paclitaxel (tumor size: 2.3 × 2.2 cm). (e) Thyroid lesion after nine cycles of zimberelimab plus nab-paclitaxel (tumor size: 3.0 × 1.6 cm). (f) Liver metastases before the first-line chemotherapy (tumor size: 4.8 × 5.8 cm). (g) Liver metastases after three cycles of gemcitabine+S-1 and one cycle of S-1 (tumor size: 1.3 × 1.1 cm). (h) Liver metastases after three cycles of gemcitabine+S-1 and one cycle of S-1 (tumor size: 2.8 × 1.8 cm). (i) Liver metastases after three cycles of zimberelimab plus nab-paclitaxel (tumor size: 1.5 × 1.4 cm). (j) Liver metastases after nine cycles of zimberelimab plus nab-paclitaxel (tumor size: 1.5 × 1.4 cm). ATC: anaplastic thyroid carcinoma; CT: computed tomography.

Figure 5.

Results of five thyroid function tests of the patient from December 2021 to August 2022. The left vertical axis reflects TSH, T4, and FT4 values, whereas the right vertical axis shows the values for T3 and FT3. T3, triiodothyronine (normal range: 1.30–3.10); T4, thyroxine (normal range: 66.00–181.00); FT3, serum-free triiodothyronine (normal range: 3.10–6.80); FT4, free thyroxine (normal range: 12.00–22.00); TSH, thyroid-stimulating hormone (normal range: 0.27–4.20).