Exploration of immunotherapy in advanced pulmonary lymphoepithelioma‐like carcinoma

Abstract

Pulmonary lymphoepithelioma-like carcinoma (PLELC) is a rare and histologically distinctive subtype of nonsmall cell lung cancer (NSCLC). High expression of programmed death ligand 1 (PD-L1) and scarcity of druggable driver mutations raise the potential of immunotherapy for advanced PELEC. However, evidence on the clinical impact of immune-checkpoint inhibitors (ICIs) remained limited and unconvincing. The present study retrospectively enrolled advanced PLELC patients who received ICIs either as up-front or salvage therapy in SYSUCC between March 15, 2017 and March 15, 2022. The comparative efficacy of chemoimmunotherapy vs chemotherapy in the first-line setting and chemoimmunotherapy vs ICIs monotherapy in the ≥2 line setting was investigated. A total of 96 patients were finally enrolled; 49 PLELC patients received immunotherapy plus platinum-based chemotherapy, while 45 patients received platinum-based chemotherapy as first-line treatment. Patientswith chemoimmunotherapy significantly obtain more survival benefits than those receiving chemotherapy (median progression-free survival [PFS]: 15.6 vs 8.6 months, P = .0015). Additionally, patients with chemoimmunotherapy obtained more PFS benefits than those with ICIs monotherapy in the ≥2 line of therapy (median PFS: 21.7 months vs 7.8 months, P = .094). A significant correlation was observed between prognostic nutritional index (PNI) and favorable treatment outcomes in patients receiving first-line chemoimmunotherapy (median PFS: 17.8 months vs 7.6 months, P < .0001). Likewise, patients in the monocyte-to-lymphocyte ratio (MLR)-high group had significantly shorter PFS than the MLR-low group (median PFS: 11.2 months vs not reached, P = .0009). Our study elucidated the superior efficacy of ICIs therapy, especially chemoimmunotherapy in advanced PLELC, which may provide new insight into the role of immunotherapy in advanced PLELC.

Development of a haematological indices-based nomogram for prognostic prediction and immunotherapy response assessment in primary pulmonary lymphoepithelioma-like carcinoma patients

“…In recent years, there has been growing interest in utilizing routine laboratory tests, including both routine blood and biochemical assessments, as clinical tools to predict clinical responses and outcomes to immunotherapies ( 17 - 20 ). For instance, Pang et al observed that in PPLELC patients receiving first-line treatment with immunotherapy plus chemotherapy, those in the high monocyte-to-lymphocyte ratio (MLR) group had significantly shorter PFS compared to the MLR-low group ( 12 ). However, these factors have often been examined in relatively small patient cohorts and were not included in multivariate analyses.…”

“…Notably, Zhou et al ( 11 ) have demonstrated the significant therapeutic efficacy of PD-1/PD-L1 inhibitors in PPLELC patients. Additionally, findings from Pang et al ( 12 ) have further demonstrated that patients receiving first-line chemoimmunotherapy experience a longer progression-free survival (PFS) compared to those undergoing traditional chemotherapy alone. Nevertheless, it is crucial to recognize that not all PPLELC patients respond positively to immunotherapy, and some may develop resistance after experiencing initial benefits, primarily due to the tumor’s inherent heterogeneity.…”

Pulmonary squamous cell carcinoma and lymphoepithelial carcinoma – morphology, molecular characteristics and differential diagnosis

“…identifying patients most probably responding to first‐line anti PD‐1/PD‐L1 therapy 139 . The addition of immunotherapy to chemotherapy results in survival benefit in patients with advanced LEC 140–142 . LEC is documented to have better survival rates compared to conventional NSCLC in both early and advanced stages.…”

Successful management of Epstein‑Barr virus‑associated severe checkpoint inhibitor‑related pneumonitis: A case report

“…However, due to persistent EBV infection, pLELC tumors always involve a strong infiltration of lymphocytes in the tumor microenvironment and high expression of programmed cell death ligand 1 (PD-L1) in tumor tissue, providing a rationale for immunotherapy. Pang et al ( 4 ) found that patients who receive chemoimmunotherapy (the current first-line treatment for advanced pLELC) gain significantly more survival benefits compared with those receiving chemotherapy.…”