Durable Response to Immunotherapy With Antiangiogenic Drug in Large-Cell Lung Carcinoma With Multiple Fulminant Postoperative Metastases: A Case Report

Abstract

Immunotherapy alone or chemo-immunotherapy has recently been recommended for treating advanced lung carcinoma in patients without driver mutations. However, the efficacy of immunotherapy and molecular mechanism in large-cell lung cancer (LCLC) remains unclear. Here, we reported a rare case of multiple fulminant postoperative body and mouth metastases in LCLC treating with combination immunotherapy. Initially, the patient was diagnosed as early stage LCLC and underwent a radical resection of the right lower lobe. Just one month later, multiple fulminant body and mouth lesions appeared in the right upper arm, right elbow, right waist, and tongue root. Meanwhile, serum neuron specific enolase (NSE) concentration dramatically increased from 12.12 to 30.14 ng/ml. Immumohistochemistry findings demonstrated moderate PD-L1 expressions with tumor proportion score (TPS), while next-generation sequencing indicated moderate tumor mutational burden (TMB) levels and gene mutations in PBRM1 L1230P and TP53 L194R of both foci. Besides, loss of heterozygosity (LOH) at human leukocyte antigen (HLA) class I (HLA-A*02:03, HLA-B*55:02 and HLA-C*12:03) were detected in the right upper arm metastasis, which may facilitate malignant postoperative metastases in this case. Notably, this patient received combination therapy with anti-PD-1 antibody sintilimab plus anlotinib, and achieved a partial response for at least 12 months. Using an integrated computational method, the mutant peptide TEIPENDIPL derived from PBRM1 L1230P was predicted to be a specific neoantigen and could still be presented by HLA-B*40:01. This case suggests that immunotherapy plus antiangiogenic drug may provide an alternative therapeutic option for advanced LCLC patients without common gene mutations.

Keywords: antiangiogenic drugs; immunotherapy; large-cell lung carcinoma; loss of heterozygosity at HLA; multiple postoperative metastases.

Figure 1

Imaging findings, pathological results and PD-L1 expressions of primary lung tumor (A) and right upper arm metastasis (B) in this LCLC case. Initial CT scan revealed a primary lung tumor in right lower lobe, and color ultrasound scan at 1 month after operation presented a right upper arm metastasis. Pathological results of both foci were confirmed LCLC with microscope magnification at 400×. Immumohistochemistry findings demonstrated PD-L1 expression with TPS 60–70% for the primary tumor and TPS 40–49% for right upper arm metastasis.

Figure 2

Clinical outcomes of NSE level (A), mouth metastasis (B) and multiple organs (C) of this LCLC case. NSE level was detected before surgery or before each cycle treatment. After radical surgery, serum NSE level dramatically increased after surgery, and gradually decreased to normal levels after three cycle treatments of antiangiogenic-immunotherapy. In addition, mouth lesion appeared after surgery and disappeared after combination antiangiogenic-immunotherapy. Besides, there were no abnormity in multiple organs and PR lasted for more than 12 months.