PMC8082155_01
(A) Mediastinal needle biopsy indicated type WHO type B3 thymoma (hematoxylin and eosin; original magnification, x50), with negative staing of CD117, but positive sating of KI67 and CK19 (immunohitochemistry; original magnification, x50). (B) PD-L1 was strongly expressed by 80% of all neoplastic thymic epithelial cells (immunohitochemistry; original magnification, x50).
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In March 2019, a 53 year-old woman was diagnosed at our institution as WHO type B3 thymoma with pleural dissemination ( Figure 1A ), and her clinical stage was Masaoka stage IVA. Immunohistochemistry showed 80% expression of PD-L1 in neoplastic thymic epithelial cells ( Figure 1B ).
Timeline scheme of major clinical event of the patient since diagnosis.
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On May 24, 2019, the patient received 200 mg of pembrolizumab, combined with paclitaxel and platinum ( Figure 2 ).
(A) Mild irAEs occurred three weeks (D21) post the administration of 200 mg pembrolizumab, which includes grade 2 to 3 liver abnormality, grade 1 kidney dysfunction, grade 1 hypothyroidism and grade 2 myocarditis. Steroids were tapered slowly over a 5-month (D150) period with gradual recovery. (B) Grade 1 liver and kidney deficiencies, grade 1 hypothyroidism and grade 2 myocarditis presented as a consequence of 100 mg pembrolizumab (D14). The irAEs reversed following immunotherapy discontinuation and steroids treatment. (Fold change was calculated as a ratio relative to upper limit of normal).
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The blood test indicated liver (grade 2-3) and kidney (grade 1) dysfunction, with ALT of 154 U/L, AST of 225 U/L, urea nitrogen of 8.50 mmol/L, and creatinine of 119 micromol/L ( Figure 3A ). TSH of 27.92 miu/L, and FT4 of 7.34 pmol/L ( Figure 3A ). Therefore, the patient was injected 40 mg methylprednisolone daily, and took 50 euthyrox once and 60 mg pyridostigmine three times daily. Besides, Troponin T (2.210 ng/ml), creatine kinase (731 U/L) and creatine kinase-MB (72 U/L) was increased ( Figure 3A ). The clinical symptoms disappeared soon, and by the end of July 2019, serum myocardial enzyme is nearly back to normal ( Figure 3A ). The patient was administered with steroid therapy, and blood levels gradually returned to normal approximately two months later ( Figure 3B ).
(A) In March 2019, the patient was diagnosed as type B3 thymoma with pleural dissemination, and her clinical stage was Masaoka stage IVA. (B) In May 2019, the evaluation of tumor response to chemotherapy is SD (RECIST). (C) In August 2019, the tumor responded to pembrolizumab. (D) In October 2019, a near complete response was achieved following a dose of pembrolizumab. (E) In March 2020, the disease progressed and 100 mg of pembrolizumab was administered. (F) The patient responded to 100 mg pembrolizumab with partial regression. (G) In September 2020, progression of the disease was found. (H) The patient responded to 100 mg pembrolizumab again.
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A rapid and dramatic response to one dose of pembrolizumab was observed and a near complete response (CR) was achieved by the end of October 2019 ( Figures 4A-D ). CT scan indicated disease progression ( Figure 4E ). Considering the potential benefit and risk of pembrolizumab, the patient was administered only 100 mg of pembrolizumab, and she presented with grade 1 liver and kidney dysfunction, grade 1 hypothyroidism and grade 2 myocarditis. Excitedly, she responded to pembrolizumab again with partial regression ( Figures 4F, G ). One hundred mg of pembrolizumab was administered to patient and the disease partially regressed ( Figure 4H ).