Complete and durable response of pulmonary large‐cell neuroendocrine carcinoma to pembrolizumab

Abstract

Background Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a rare and aggressive tumor with a poor prognosis and standard therapy has not yet been established. Case A 65‐year‐old male with a cough for 2 months presented to our hospital. He was clinically diagnosed with non small cell lung cancer cT3N1M0 stage IIIA and underwent right pneumonectomy. The final diagnosis was pulmonary LCNEC pT3N1M0 stage IIIA. Multiple subcutaneous masses were detected 4 months after surgery, and biopsy revealed postoperative recurrence and metastasis. Chemotherapy with carboplatin plus etoposide was initiated. Subcutaneous masses increased and multiple new brain metastases developed after two cycles. Additional tests revealed that epidermal growth factor receptor and anaplastic lymphoma kinase were negative, and the programmed death ligand 1 (PD‐L1) expression rate in tumor cells was 40% (22C3 clones). The primary cells infiltrating the tumor were CD3‐positive T cells and CD138‐positive plasma cells. Second‐line treatment with pembrolizumab was started. The shrinkage of subcutaneous masses was observed after one cycle, and the tumor had completely disappeared after six cycles. Treatment was continued for approximately 2 years. This response has been maintained for 4 years and is still ongoing. Conclusion Pembrolizumab may be used as a treatment option for pulmonary LCNEC.

A single dose of pembrolizumab treatment causing a profound and durable response in lung cancer

“…The same case report has been made for lung cancer. 9 , 10 Tumor‐infiltrating plasma cells are a favorable prognostic factor in lung cancer. 11 , 12 In various cancer types, the presence of B cells and tertiary lymphoid structures is associated with longer disease‐free and overall survival in patients treated with ICI.…”

Large cell neuroendocrine carcinoma of the lung controlled for 4 years by a single administration of pembrolizumab: A case report

“…PD‐L1 expression on tumor cells, TILs, TLSs, and the tumor mutation burden has been reported as possible predictive biomarkers for ICI efficacy. In fact, some tumors that respond to therapy show high lymphocyte infiltration 4 . PD‐L1 is reportedly expressed in ~10% to 20% of pulmonary LCNECs 9 .…”

“…However, a recent study indicated that there may not be an accurate correlation between the PD‐L1 expression level and effect of ICIs 10 . Among the reported patients with LCNEC who achieved CR by ICIs, many CD138‐positive plasma cells were observed in their tumors 4 . Tumor‐infiltrating plasma cells are regarded as a favorable prognostic factor in lung cancer 11 .…”

“…In fact, some tumors that respond to therapy show high lymphocyte infiltration. 4 PD‐L1 is reportedly expressed in ~10% to 20% of pulmonary LCNECs. 9 However, a recent study indicated that there may not be an accurate correlation between the PD‐L1 expression level and effect of ICIs.…”

“…LCNEC is generally reported to have a poor prognosis, and its treatment is challenging because the only definitive therapy is complete resection. Immune checkpoint inhibitors (ICIs) were recently approved for treatment of lung cancer and have reportedly had remarkable clinical effects in some patients with LCNEC 4 . We describe a patient with postoperative recurrence of LCNEC who achieved long‐term survival without relapse after just one dose of pembrolizumab.…”