IntroductionWe evaluated the efficacy and safety of first-line treatment with a programmed death-ligand 1 (PD-L1) inhibitor plus platinum-based chemotherapy versus chemotherapy alone in patients aged ≥75 years with extensive-stage small cell lung cancer (ES-SCLC).MethodsWe retrospectively analyzed the patients with ES-SCLC treated within the Niigata Lung Cancer Treatment Study Group between August 2019 and April 2024.ResultsAmong 364 consecutive patients were enrolled. After excluding 21 patients with prior treatment or ineligible histological types, 343 patients were included in the analysis. Of these, 133 were aged ≥75. Compared with chemotherapy alone, administering a PD-L1 inhibitor with chemotherapy significantly improved the median overall survival among elderly patients (13.9 vs. 8.4 months; hazard ratio, 0.543; P = 0.0277). The median progression-free and overall survivals were similar between the ≥75-year and <75-year groups treated with PD-L1 inhibitor plus chemotherapy (4.9 vs. 4.8 months; P = 0.7611 and 13.6 vs. 15 months; P = 0.732, respectively). Immune-related adverse events (irAE) of ≥grade 3 occurred in 4 and 12 patients (P = 0.7823), and non irAE of ≥grade 3 occurred in 47 and 103 patients (P = 0.5247) in the ≥75-years and <75-years subgroups, respectively.ConclusionsIn this retrospective study, among patients aged ≥75 with ES-SCLC, the addition of a PD-L1 inhibitor to platinum-based chemotherapy was associated with significantly longer overall survival. Progression-free and overall survival outcomes were comparable between elderly and younger patients, and the incidence of adverse events of ≥grade 3 did not differ according to age.

RATIONALE AND OBJECTIVES:Immune checkpoint inhibitors (ICIs) have improved survival in non-small cell lung cancer (NSCLC); however, predicting immune-related adverse events (irAEs) remains a clinical challenge. We previously showed that high 18F-fluorodeoxyglucose (18F-FDG) uptake in the non-cancerous lung (NCL) on PET/CT is associated with the risk of interstitial lung disease. This study further investigated whether NCL FDG uptake predicts the risk of irAEs, including both ILD and non-ILD events, as well as survival outcomes in patients with lung cancer receiving ICIs. MATERIALS AND METHODS:We retrospectively analyzed 165 patients with lung cancer who underwent PET/CT before ICI therapy. FDG uptake in the NCL, defined as the lung contralateral to the primary tumor and free of metastatic lesions, was quantified using AI-based segmentation. Total glycolytic activity in the NCL (NCL-TGA1.0) was calculated as the product of the mean SUV and the lung volume, both measured within regions with SUV ≥1.0. Associations of NCL-TGA1.0 with irAE incidence and survival outcomes were assessed using multivariable and Kaplan-Meier analyses. RESULTS:High NCL-TGA1.0 (≥149.45) was independently associated with increased risk of irAEs in multivariate analysis (odds ratio [OR]: 6.910; p=0.005), including non-ILD irAEs (OR: 4.244; p=0.020). In survival analysis of 84 unresectable NSCLC patients, high NCL-TGA1.0 was associated with significantly shorter progression-free survival (median: 4.30 vs. 9.90 months, p=0.007) and overall survival (median: 6.93 vs. 22.03 months, p=0.029). CONCLUSION:High FDG uptake in the NCL is a predictor of irAEs and poor survival in patients with lung cancer receiving ICIs. These results may help to identify high-risk patients prior to treatment.

Although programmed cell death-1 (PD-1) inhibitors have shown promising and durable responses in patients with several types of cancer, many patients show resistance to PD-1 inhibitors. Recent evidence has demonstrated that immunosuppressive cells are induced in tumor microenvironment and inhibit the anti-tumor effects of anti-PD-1 monoclonal antibody (αPD-1 mAb). To investigate whether nintedanib-a multi-tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor, fibroblast growth factor receptor, and platelet-derived growth factor receptor-suppresses immunosuppressive cells and enhances the anti-tumor effects of αPD-1 mAb in preclinical models, flowcytometry, immunohistochemistry, and RNA sequencing of tumor-tissue, tumor-draining lymph nodes, spleens were conducted. RNA sequencing of murine tumor tissues revealed that nintedanib decreased the gene signatures related to myeloid-derived suppressor cells (MDSCs) and cancer-associated fibroblasts (CAFs). Flow cytometry showed that nintedanib significantly decreased the MDSC and CAF percentage in tumor-bearing hosts and increased IFN-ϒ+CD4+ and CD8+ T cells infiltrating into tumors. Immunohistochemical analysis demonstrated that nintedanib treatment significantly increased the number of CD8+ T cells in the internal area of the tumor. Adding nintedanib to anti-PD-1 mAb therapy significantly inhibited in vivo tumor progression. These results indicate that nintedanib suppresses MDSCs and CAFs by inhibiting VEGFR-, PDGFR-, and FGFR-mediated signaling, thereby increasing effector T-cell infiltration into tumors and enhancing the anti-tumor effects of αPD-1 mAb therapy.

Introduction Immunosuppressive cytotoxic chemotherapy for malignant tumors may activate underlying nontuberculous mycobacteria (NTM) infections. However, chemotherapy-induced NTM pulmonary disease exacerbations have not been systematically evaluated. Thus, in this novel study, we aimed to evaluate the effects of chemotherapies on patients with concomitant NTM pulmonary diseases and malignant tumors. Methods In this single-center study, we retrospectively reviewed medical records of patients with histopathologically proven malignant tumors and concurrent NTM pulmonary disease between September 2012 and September 2022. Data, including clinical history, imaging, tumor type, NTM etiological data, and treatment course, were collected. Results Of the 193 patients diagnosed with NTM pulmonary diseases, 54 (28%) had concurrent malignant tumors. Eighteen of these patients received at least one chemotherapeutic agent, and two (11%) developed NTM pulmonary disease exacerbations. One patient with early-stage breast cancer developed an NTM pulmonary disease exacerbation after receiving two cycles of adjuvant paclitaxel therapy. Another patient with malignant lymphoma developed an NTM pulmonary disease exacerbation 81 months after receiving rituximab-containing chemotherapy. Both patients responded to anti-NTM therapy. The patient with malignant lymphoma received ethambutol and clarithromycin during chemotherapy. Conclusions Despite the small sample size, this hypothesis-generating study suggests that chemotherapy may exacerbate NTM pulmonary disease. As the first to investigate this interaction in patients with both conditions, the findings highlight the need for large prospective studies.

BACKGROUND:The definition of clinical remission has not been fully standardized. The Japanese guideline adopts a criterion of Asthma Control Test (ACT) score ≥23, compared with the global threshold of ≥20. In this study, we focused on patients with ACT scores of 20-22 to clarify their clinical characteristics. METHODS:We analyzed asthma survey data from Niigata and Kumamoto for 2021 and 2023, respectively. A total of 611 patients with complete clinical data were included. Japanese clinical remission (jCR) was defined as ACT ≥23, no OCS use, no exacerbations, and %FEV1 ≥80%. Patients who met any of the criteria ACT <20, OCS use, exacerbations in the previous year, or %FEV1 <80% were classified as non-clinical remission (nCR). Patients with an ACT of 20-22 who otherwise met the remission criteria were defined as global-clinical remission (gCR). RESULTS:In 2021, 248, 276, and 87 patients achieved jCR, nCR, and gCR. Compared with the jCR group, the gCR group showed no significant differences in severity, but had significantly higher Patient Health Questionnaire (PHQ-9) and Nijmegen Questionnaire (NQ) scores, similar to the nCR group. The frequency of exacerbations in the following year was lower in the gCR group than in the nCR group. CONCLUSIONS:Although patients with gCR had a lower disease severity than those with nCR, their PHQ-9 and NQ scores were higher than those with jCR, suggesting that psychological factors may hinder remission. Specific management of strategies for patients with gCR may be required in addition to pharmacological care.

ABSTRACT Background Durvalumab maintenance following concurrent chemoradiotherapy (CCRT) is the standard treatment for unresectable stage III non‐small cell lung cancer (NSCLC); however, some patients discontinue treatment before completing 12 months. We explored whether pretreatment peripheral blood inflammatory and nutritional markers are associated with durvalumab non‐completion. Methods We retrospectively reviewed patients with locally advanced NSCLC who initiated durvalumab between August 2018 and April 2024. Laboratory data obtained within 7 days before the first dose were analyzed. Completion was defined as 12 months (365 days) of treatment. Routine laboratory parameters and inflammatory/nutritional indices were compared between completers and non‐completers. Exploratory multivariable logistic regression and clinically adjusted sensitivity analyses were performed. Results Eighty patients were included: 36 completers and 44 non‐completers. Durvalumab was discontinued because of disease progression (n = 24), radiation pneumonitis (n = 14), immune‐related adverse events (n = 5), and aspiration pneumonia (n = 1). Conventional inflammatory indices did not differ between groups. In the primary exploratory multivariable model, a higher albumin‐to‐globulin (A/G) ratio was associated with durvalumab completion (OR, 9.74; 95% CI, 1.01–93.9; p = 0.048), whereas RDW‐SD showed a non‐significant inverse association with completion (OR, 0.942; 95% CI, 0.883–1.01; p = 0.076). After adjustment for age, ECOG performance status, and histology, these associations were not statistically significant. Conclusions Lower A/G ratio and higher RDW‐SD before durvalumab initiation may be associated with non‐completion. Given the exploratory design, limited sample size, attenuation after clinical adjustment, and heterogeneous reasons for discontinuation, these findings require external validation.

Pulmonary pleomorphic carcinoma (PPC) is a subtype of sarcomatoid carcinoma that accounts for 0.1-0.3% of all lung cancer cases. PPC is typically resistant to chemotherapy and radiotherapy, and no standard treatment protocols are currently established. Moreover, to the best of our knowledge, the effectiveness of the MET inhibitor tepotinib in the treatment of PPC has not yet been reported. Herein, the present study describes the case of a 75-year-old woman with PPC harbouring a MET exon 14 skipping mutation who was successfully treated with tepotinib as first-line systemic therapy, followed by pembrolizumab as subsequent immune checkpoint inhibitor therapy. Although the tumour relapsed 4 months postoperatively, treatment with tepotinib resulted in a favourable response and subsequent pembrolizumab therapy achieved a durable response. This case suggests that patients with sarcomatoid carcinoma, which is generally associated with a poor prognosis, may experience improved outcomes with the use of molecular targeted therapies and immune checkpoint inhibitors.

INTRODUCTION:Mycobacterium avium lung disease (MA-LD) poses significant challenges in predicting disease progression. This study aimed to characterize the genomic diversification of M. avium and define its relationship to disease progression. METHODS:We investigated the whole-genome sequence data of 36 M. avium clinical strains. Comparative analyses of genomic structure and sequence were undertaken between subjects with progressive disease (PD) and those with stable disease (SD). RESULTS:M. avium strains were classified into two types: type A and type nonA, according to the 1.4-Mb genomic inversion. All type A strains (n = 15) were isolated from PD subjects, and type nonA strains were referred to as type B and type C strains and were isolated from PD subjects (n = 10) and SD subjects (n = 11), respectively. The three strain types (A/B/C) were mainly distributed in distinct clusters of the amino acid identity-based phylogenetic tree. We further identified the specific set of single-nucleotide variations discriminating between type B and type C strains. The three M. avium genotypes were associated with disease progression in an independent validation cohort of 32 subjects. CONCLUSIONS:The genomic types of M. avium may represent a valuable biomarker for estimating the risk for MA-LD progression.

Sarcopenia has been reported that as a prognostic factor in patients with non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs), mainly based on retrospective, imaging-based analyses. However, its prognostic value has not been prospectively evaluated. In this prospective study we investigated the clinical impact of sarcopenia and explored circulating proteins associated with muscle loss and ICI outcomes. Patients with advanced NSCLC who received ICIs as first-line therapy were enrolled. Before treatment initiation, muscle mass was assessed using bioelectrical impedance analysis, together with grip strength, walking speed, and physical activity. Pretreatment plasma samples were subjected to comprehensive protein profiling. Between October 2019 and August 2022, 41 patients were enrolled. Bothe overall survival and progression-free survival were significantly shorter in patients with sarcopenia. Notably, patients with pre-sarcopenia, defined as reduced muscle mass without impairment of muscle strength or physical performance, also exhibited poor clinical outcomes. Protein analysis identified penraxin-3 as being significantly associated with muscle loss and overall survival. These findings demonstrate, for the first time in a prospective setting, that even pre-sarcopenia is associated with poor prognosis in NSCLC patients treated with ICIs, and suggest that pentraxin-3 may serve as a biomarker linking sarcopenia to unfavorable outcomes.

There is no effective treatment for KRASG12D-mutant tumors. Immune checkpoint inhibitors (ICIs) have improved survival rates for lung cancer patients, but they are less effective in non-small cell lung cancer (NSCLC) with KRASG12D mutations. MRTX1133 is a selective inhibitor of KRASG12D undergoing early clinical trials. This study aimed to investigate the immune landscape of a KRASG12D-mutant lung cancer mouse model and evaluate whether MRTX1133 could induce antitumor immunity. We also assessed whether MRTX1133 has anti-proliferative effects and can promote antitumor immunity in human KRASG12D-mutant lung cancer cell lines. We generated conditional KRASG12D-mutant mice by crossing CCSP-rtTA/TetO-Cre and LSL-KRASG12D knock-in mice, inducing lung-specific tumors with doxycycline-containing food. MRTX1133 was administered intraperitoneally at 10 mg/kg once daily for 4, 8, or 12 days. After treatment, lungs and spleens were collected for flow cytometry analysis, and lung cells from the 4-day treatment group underwent RNA sequencing. Human KRASG12D-mutant lung cancer cell lines (A427 and SK-LU-1) were treated with MRTX1133 for RNA-Seq, differential gene expression analysis, and gene set enrichment analysis (GSEA). CCL20 protein levels were further validated by Western blotting and ELISA. Longer doxycycline exposure increased regulatory T cell (Treg) infiltration in lung tumors. Additionally, immune checkpoint molecules (ICMs) such as PD-L1, PD-1, TIGIT, TIM-3, and LAG-3 were upregulated in CD4+ and CD8+ T cells. MRTX1133 treatment inhibited KRASG12D tumor progression, reduced Treg percentages, and decreased PD-1 expression in CD4+ and CD8+ T cells. It also increased tumor-specific CD8+ effector T cell infiltration in lung tumors, and interferon-gamma was enriched in MRTX1133-treated lung cells. In human KRASG12D-mutant lung cancer cells, MRTX1133 increased immune-related gene expression and decreased cell division-related genes in both cell lines. GSEA showed enrichment of interferon-gamma and interferon-alpha in MRTX1133-treated SK-LU-1 cells, while DMSO-treated cells showed enrichment of cell division genes. Elevated CCL20 levels were confirmed in the SK-LU-1 MRTX1133-treated group. KRASG12D-mutant lung tumors in mice exhibited T cell exhaustion. MRTX1133 showed therapeutic efficacy in the preclinical KRASG12D-mutant lung cancer model, possibly by enhancing antitumor immune responses along with oncogenic signaling inhibition. In human KRASG12D-mutant lung cancer cell lines, MRTX1133 reduced cell proliferation and increased antitumor cytokine expression, especially in SK-LU-1 cells. These findings may support the development of new immunotherapeutic strategies for patients with KRASG12D-mutant lung cancer. Kunihiro Shono, Satoshi Watanabe, Takaaki Masuda, Tomoya Wakabayashi, Ryo Yamazaki, Yumi Ando, Ryo Suzuki, Susumu Tanaka, Tomohiro Tanaka, Koichiro Nozaki, Yu Saida, Naohiro Yanagimura, Masashi Arita, Miyuki Sato, Riuko Ohashi, Kenjiro Shima, Yosuke Kimura, Nobumasa Aoki, Yasuyoshi Ohshima, Toshiyuki Koya, Toshiaki Kikuchi. The effects of MRTX1133 on antitumor immunity in KRASGD-mutant lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4531.

Our previous prospective study demonstrated that non-small cell lung cancer (NSCLC) patients (pts) with pre-sarcopenia or sarcopenia exhibited poor responses to immune checkpoint inhibitors (ICIs). In this study, we evaluated the relationship between immune status and the efficacy of ICIs in NSCLC pts with sarcopenia. Pts with stage IV or recurrent NSCLC receiving ICI as first-line treatment at Niigata University Medical and Dental Hospital were eligible. Sarcopenia and pre-sarcopenia were diagnosed with physical performance and skeletal muscle mass. Before ICI treatments, peripheral mononuclear blood cells (PBMCs) were collected, and immune phenotypic data was obtained by flow cytometry. PBMCs were obtained from 34 pts from December 2021 through September 2024. Six patients and 7 patients were diagnosed with sarcopenia and pre-sarcopenia, respectively. Pts with a higher percentage of Lineage-CD11b+CD14+CD33+DRlow monocytic myeloid-derived suppressor cells (M-MDSCs) or Lineage-CD11b+CD15+CD33+DRlow polymorphonuclear (PMN)-MDSCs significantly shorter OS (median, 12 months (95% CI, 2.9-26.5) vs 33.1 months (95% CI, 11.4-NR); HR 2.7; P=0.035) after ICI treatments. Further, pts with PD-L1+ cells in MDSCs also had poor OS (median, 12 months (95% CI, 2.9-26.5) vs 33.1 months (95% CI, 11.4-NR); HR 2.6; P=0.0387). The higher percentage of M-MDSC (P=0.0534) and the presence of PD-L1+ cells in MDSCs (P=0.0473) tended to be associated with pts with sarcopenia or pre-sarcopenia. MDSCs may play a critical role in immune suppression in NSCLC pts with sarcopenia and could be associated with poor OS following ICI treatment. To improve the survival outcome of pts with sarcopenia, it is essential to establish strategies to overcome MDSC-mediated immune suppression. Ryo Yamazaki, Satoshi Watanabe, Takaaki Masuda, Tomoya Wakabayashi, Yumi Ando, Kunihiro Shono, Naohiro Yanagimura, Masashi Arita, Miyuki Sato, Tomohiro Tanaka, Koichiro Nozaki, Yu Saida, Kenjiro Shima, Yosuke Kimura, Nobumasa Aoki, Yasuyoshi Ohshima, Toshiyuki Koya, Toshiaki Kikuchi. The correlation between immune status and the therapeutic efficacy of immune checkpoint inhibitors in patients with non-small cell lung cancer with sarcopenia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 7127.

INTRODUCTION:The safety of administering immune checkpoint inhibitors (ICIs) after talc pleurodesis, particularly the impact of talc on the development of immune-related interstitial lung disease (ILD), remains unclear. METHODS:We retrospectively analysed patients with primary lung cancer or malignant pleural mesothelioma who received ICIs within 90 days of talc pleurodesis at facilities participating in the Niigata Lung Cancer Treatment Study Group between November 2016 and June 2023. RESULTS:A total of 52 cases were included, with 17 patients (32.7 %) developing ILD following ICI administration. The median time to ILD onset after ICI administration was 62 days. The median overall survival was 6 months in patients who developed ILD and 16.4 months in those who did not (P = 0.081). Among the five patients with pre-existing interstitial changes, four (80.0 %) developed ILD after ICI administration, identifying a high-risk subgroup. CONCLUSION:A high incidence of ILD was observed in patients who received ICI therapy after talc pleurodesis. Additionally, overall survival tended to be shorter in patients who developed ILD.

Background:Immune checkpoint inhibitors (ICIs) in combination with chemotherapy have demonstrated efficacy in the treatment of non-small cell lung cancer (NSCLC) with a programmed death ligand 1 (PD-L1) tumor proportion score (TPS) of 1-49%. However, older patients remain underrepresented in clinical trials, and optimal treatment strategies for this population remain unclear. This study sought to evaluate the efficacy and safety of first-line treatment with either platinum-based chemotherapy alone (Chemo) or in combination with ICIs (ICI/Chemo) in older patients with NSCLC who have low PD-L1 expression. Methods:This retrospective multicenter study included patients diagnosed with advanced NSCLC (stage IIIB-IV) with a PD-L1 TPS of 1-49% from 19 Japanese institutions. We examined the relationship between baseline patient characteristics and treatment outcomes within each group. Propensity score matching (PSM) was used to balance patient characteristics between the ICI/Chemo and Chemo groups. Results:We evaluated data from 613 patients, finding that the ICI/Chemo group (n=370) exhibited significantly longer median progression-free survival (PFS) and overall survival (OS) compared to the Chemo group (n=243). Among the 613 patients, 152 were aged ≥75 years. Of these, 63 received Chemo, while 89 underwent ICI/Chemo as first-line treatment. In this older cohort, ICI/Chemo significantly improved median PFS; however, no significant difference was observed in OS. Nonetheless, the incidence of grade ≥3 adverse events and pneumonitis of any grade was higher in the ICI/Chemo group compared to the Chemo group among older patients. Multivariate analysis using Cox proportional hazards models indicated that Eastern Cooperative Oncology Group performance status (ECOG PS) was significantly associated with PFS and OS. In older patients with ECOG PS 0, ICI/Chemo showed significant PFS benefits; in those with ECOG PS 1, both the PFS and OS were similar between the two groups. Conclusions:ICI combined with chemotherapy may be a potentially effective treatment strategy for older patients with NSCLC and low PD-L1 expression. However, compared with the overall population, the benefits of adding ICI to chemotherapy were decreased, while the risk of toxicity may increase, making appropriate patient selection crucial for this population. Particularly, in patients with ECOG PS 1, the additional benefit of ICI over chemotherapy was minimal in terms of efficacy, suggesting that the introduction of ICI combined with chemotherapy should be carefully considered for this patient population.

Chemoimmunotherapy is recommended for patients with non-small cell lung cancer (NSCLC) with low PD-L1 expression, but the effect of additional immunotherapy is heterogeneous in this population. To identify patients who do not benefit from the addition of immune checkpoint inhibitors (ICI) to chemotherapy, we conducted a retrospective study at 19 institutions in Japan. We analyzed 851 patients with advanced NSCLC with a PD-L1 tumor proportion score of 1% to 49% who received chemoimmunotherapy (n = 504) or chemotherapy (n = 347) between March 2017 and June 2022. After adjustment by propensity score matching, the median overall survival (OS) was 22.3 months in the chemoimmunotherapy group and 17.0 months in the chemotherapy-alone group (P = 0.01). Multivariate analysis showed that among 12 clinical factors, liver metastases (P = 0.001) and history of antibiotic use (P = 0.02) were independently associated with shorter OS in the chemoimmunotherapy group. Patients with liver metastases (OS, P = 0.4; progression-free survival, P = 0.06) or history of antimicrobial use (OS, P = 0.24; progression-free survival, P = 0.09) did not benefit from the addition of ICI to chemotherapy. Patients with a history of antimicrobial use experienced more severe pneumonitis with chemoimmunotherapy than all patients (P = 0.04). This cohort study showed that liver metastases and prior antimicrobial therapy are the most important clinical factors that attenuate the efficacy of chemoimmunotherapy in patients with low PD-L1 expression.Significance: This study shows that liver metastases and prior antibiotic use are key factors for chemoimmunotherapy in advanced NSCLC cases with low PD-L1 expression. They reduce the benefit of adding ICIs to chemotherapy, underscoring the need for new strategies to improve ICI efficacy in patients.

Background:Severe immune-related adverse events (irAEs) are often associated with combined immunotherapy and chemotherapy in patients with non-small cell lung cancer (NSCLC). However, their effect on clinical outcomes has yet to be fully elucidated. In this study, we investigated the impact of irAEs, particularly pneumonitis, on clinical outcomes in patients receiving combined immunotherapy and chemotherapy for NSCLC. Methods:We retrospectively enrolled 850 patients with programmed cell death ligand-1 (PD-L1) 1-49% advanced NSCLC who were treated with chemotherapy alone or with combined immunotherapy and chemotherapy as first-line treatment at 19 different institutions in Japan between March 2017 and June 2022. Using data from their medical records, we examined the type and severity of irAEs and their association with clinical outcomes, including overall survival (OS) and progression-free survival (PFS). Results:OS and PFS were not significantly different between patients with and without severe irAEs. However, in the group receiving combined immunotherapy and chemotherapy, those who developed pneumonitis within 42 days of treatment initiation had shorter OS and PFS, irrespective of the pneumonitis grade, and a worse prognosis than those who received chemotherapy alone. Additionally, early-onset pneumonitis was more likely in patients aged >75 years, those with high lactate dehydrogenase levels, and those receiving steroids or immunosuppressants, suggesting that these factors may contribute to the risk of early-onset pneumonitis. Conclusions:Early-onset pneumonitis is a poor prognostic factor in patients with PD-L1 1-49% advanced NSCLC receiving combined immunotherapy and chemotherapy. Further large-scale observational studies are warranted to confirm these findings. Keywords:Non-small cell lung cancer (NSCLC); severe immune-related adverse events (irAEs); pneumonitis.