PMC7681247_01
The dynamic changes in number of B, T, and platelet pre- and post-rituximab in combination with lenalidomide treatment. (A, B) Whole blood cells, obtained from the patient before and after each cycle of treatment with rituximab plus lenalidomide, were stained with CD19 or CD3 monoclonal antibodies, and analyzed using flow cytometry. Shown are frequencies, which were expressed as a percentage of nuclear cells. (C) Routine blood examinations were performed before and after each cycle of treatment with rituximab plus lenalidomide. Shown are the number of platelets, which were expressed as cells/L.
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The platelet number resumed to normal level, the B cell number decreased to zero level, while the T cell number was unaffected ( Figure 1 ). Bone scans showed that bone metabolism was active in the right clavicle, the ninth and twelfth thoracic vertebra, and the first and second lumbar vertebrae, indicating bone metastasis ( Supplemental Figure 1 ).
Representative images of PD-L1 and PD-1 expression on tumor tissues. (A) Tumor sections were stained with the PD-L1 IHC 22C3 pharmDx (Agilent) and the IVD VENTANA PD-L1 (SP263). (B) Tumor sections were stained with the PD-1 antibody. Magnification (200x).
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Results from PD-L1 immunohistochemical staining showed that the rate of PD-L1 positive tumor cells was 90%, and that of PD-1 positive cells less than 1% ( Figure 2 ).
The radiological tumor evolution. Shown are two different views of chest computed tomography (CT) slices (A, C, E, G: Chest window; B, D, F, H: Lung window). (A, B) CT scan showing mass of the lung adenocarcinoma pre-treatment of PD-1 inhibitor. (C-H) CT scan shows a partial response after 2 (C, D), 4 (E, F), and 6 (G, H) cycles of immunotherapy. The arrow shows the changes of the left lung mass during the PD-1 administration.
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After four cycles, a CT scan revealed a 38.4% reduction in the soft tissue mass shadow in the lower lobe of the left lung to about 27 x 32 mm, reaching a partial response ( Figure 3 ).
A detailed clinical timeline is displayed. On October 20, 2017, the patient was hospitalized. After a series of examinations, the patient was diagnosed with advanced lung adenocarcinoma without driver gene mutations. In December, 2017, the patient was started on a chemotherapy regimen containing paclitaxel/carboplatin plus bevacizumab for 4 cycles. Due to grade III thrombocytopenia, the regimen was subsequently switched to pemetrexed plus bevacizumab for 3 cycles from February, 2018. Although a CT scan revealed a partial response after these cycles of treatments, progressive thrombocytopenia occurred. After extensive examination, the patient was diagnosed marginal zone lymphoma in June, 2018. After 5 cycles of rituximab in combination with lenalidomide treatment, lymphoma was in complete remission. However, a CT in February, 2019 demonstrated disease progression. From March, 2019 to October, 2019 the patient was treated with sintilimab, a PD-1 inhibitor, of 200 mg every 3 weeks. CT imaging demonstrated significant treatment responses.
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At the time of writing, treatment with immunotherapy is ongoing ( Figure 4 ).