Immunotherapy and PD-L1 Tumor Expression in Moroccan Non-Small Cell Lung Cancer Patients with Various Metastasis.

inroductionThe question of whether tumor expression of PD-L1 and the presence of distant metastasis could influence the efficacy of immunotherapy represents a major challenge and needs to be further elucidated. The aim of this study is to evaluate the predictive significance of tumor expression of PD-L1 as well as the number and site of metastasis in non-small cell lung cancer (NSCLC) among Moroccan patients treated with immunotherapy. MATERIAL AND

methodsBetween January 2019 and February 2023, we recruited Moroccan patients with metastatic NSCLC. All were treated with immunotherapy, either as monotherapy or in combination with chemotherapy. Immunohistochemistry was used to assess PD-L1 (clone 22C3) and ALK (clone D5F3) status. EGFR status was established by qPCR. Tumor PD-L1 expression was classified into 2 levels: TPS <1% (negative expression) and TPS ≥1% (positive expression). Statistical analysis was performed using SPSS Statistics V.21 software.

resultsThe median age of patients (N=40) was 67 years (39- 92 years) and the sex ratio was 9. Disease dissemination revealed that 22.5% (N=9) of patients had a metastatic burden ≥ 3 (MB≥3). As for the sites of metastasis, the results showed that 20% (N=8), 10% (N=4), 42.5% (N=17), 22.5% (N=9), 27.5% (N=11), 45% (N=18) and 27.5% (N=11) of patients had developed lymph node, liver, bone, brain, pleural, contralateral lung and adrenal metastasis respectively. Positive PD-L1 expression was significantly associated with shorter overall survival (OS = 17.19 vs. 28.85 months, p=0.01). High metastatic burden (MB ≥ 3) was associated with lower objective response rate (ORR), shorter progression-free survival (PFS), and reduced OS, respectively (ORR = 0 vs. 58.06%, p=0.002; PFS = 10.23 vs. 25.27 months, p=0.001; and OS = 11.60 vs. 27.91 months, p=0.003). Only the presence of osseous metastasis was significantly associated with lower ORR, shorter PFS, and OS compared to other metastatic locations (ORR = 5.88 vs. 73.9%, p=0.000; PFS = 10.72 vs. 31.33 months, p=0.000; and OS = 11.39 vs. 36.17 months, p=0.000). Finally, the presence of hepatic metastasis was significantly associated with shorter PFS (10.75 months) compared to those without hepatic metastasis (22.53 months) (p=0.046). Finally, the results of the multivariate analysis revealed that the presence of bone metastasis was strongly correlated with a significant decrease in progression-free survival (p=0.001) as well as overall survival (p=0.002).

conclusionOur results suggest that tumor expression of PD-L1 and metastatic burden should play a significant role in predicting the response to immunotherapy. Furthermore, it is important to note that the presence of osseous and hepatic metastasis could negatively influence the clinical outcomes of immunotherapy.