Case Report: Therapeutic Response to Chemo-Immunotherapy in an Advanced Large Cell Lung Carcinoma Patient With Low Values of Multiple Predictive Biomarkers

Abstract

Immune checkpoint inhibitors have revolutionized the treatments of lung cancers, and multiple predictive biomarkers alone or in combination help clinicians with the appropriate therapeutic selections. Recently, chemo-immunotherapy has been recommended for treating advanced non-small cell lung cancers in patients without driver mutations. However, the clinical relevance of predictive biomarkers and the treatment efficacy of chemo-immunotherapy in large cell lung carcinoma (LCLC) remain unclear. Here, we reported a rare case of LCLC with none driver gene mutations and low values of multiple predictive biomarkers. These biomarkers included a low PD-L1 expression of 5-10%, a low tumor mutational burden (TMB) of 2.5 muts/mb, a low CD8(+) tumor-infiltrating lymphocyte density of 147.91 psc/mm². After one-cycle chemotherapy, the patient progressed rapidly and then was switched to pembrolizumab combining paclitaxel plus cisplatin. Interestingly, he achieved a partial response after two cycles of chemo-immunotherapy, showing multiple lymph nodes obviously shrunk on CT scan, and other clinical symptoms were relieved when compared with the baseline findings. After five cycles of chemo-immunotherapy, this advanced patient still benefited and was changed to maintenance immunotherapy monotherapy. This case suggests that chemo-immunotherapy may provide an effective therapeutic option for those LCLC patients with low values of multiple predictive biomarkers, particularly for those who progressed from first-line classical treatments.

Keywords: CD8(+) tumor-infiltrating lymphocytes; PD-L1 expression; chemo-immunotherapy; large cell lung carcinoma; predictive biomarker; tumor mutational burden.

Figure 1

Pathologic findings and CT findings. (A) H&E stain demonstrated poorly differentiated carcinoma (×100). (B) Immunohistochemical stain showed a low positive PD-L1 expression of TPS 5–10% (×400). (C) Immunohistochemical stain indicated a low CD8(+) TIL density of 147.91 psc/mm² (×400). (D) Pulmonary lesions progressed in CT chest after one cycle of chemotherapy. (E) Pulmonary lesions lessened after two cycles of chemo-immunotherapy. (F) Pulmonary lesions shrunk after four cycles of chemo-immunotherapy.

Figure 2

Time line and therapeutic regime. LCLC, large cell lung cancer; PR, partial response; PD, progressive disease; chemo, chemotherapy of pemetrexed (800 mg/kg, d1) plus lobaplatin (50 mg, d1) and endosta (30 mg/day, 7days); chemo-immu, chemo-immunotherapy of pembrolizumab (200 mg/kg, d1) combining paclitaxel (400 mg/kg, d1) plus cisplatin (120 mg/kg, d2); immu, immunotherapy monotherapy of pembrolizumab (200 mg/kg, d1). This patient was diagnosed as stage IV (cT4N3M1) LCLC for diseased lungs and multiple metastases or lymph node enlargements based on fiberoptic bronchoscopy and CT imaging, together with pathological findings showing poor differentiated large cell tumor. Due to no driver gene mutations, this patient was initiated with classical chemotherapy. After disease progression, he turned to chemo-immunotherapy regime for a positive PD-L1 expression (TPS 5–10%). Compared with the baseline findings of fiberoptic bronchoscopy and CT imaging, this advanced LCLC patient benefited from chemo-immunotherapy and the following maintenance immunotherapy monotherapy when rapidly progressed after classical chemotherapy till November 2020.