{
  "abstract": "Background Tertiary lymphoid structures containing B cells and plasma cells correlate with improved immunotherapy outcomes across various solid tumor types. However, it remains unclear whether these cells play a direct role in tumor immunity or simply act as markers of a robust anti-tumor immune response. Studying patients with naturally occurring or therapeutically induced B cell deficiencies may provide insight into the necessity of B cells for response to immune checkpoint inhibitors (ICIs).Methods We analyzed the Flatiron Health Research Database, including electronic health records from adults aged 40–85 years diagnosed with primary NSCLC between 2011 and 2023. Patients with any history of B cell malignancy were excluded. Individuals with documented B cell or IgG deficiency, including hereditary and nonfamilial hypogammaglobulinemia, common variable immunodeficiency (CVID) and other immunodeficiencies with predominantly antibody defects, and those who underwent rituximab-based B cell depletion therapy within five years prior to lung cancer diagnosis, were identified. Each patient was matched to four controls by sex, age, race, smoking status, socioeconomic status, practice type and baseline ECOG performance status. Overall survival (OS) was compared between the B cell deficient/depleted patients and matched controls using Cox proportional hazards models stratified by matched set and adjusted for the presence of chronic obstructive pulmonary disease (COPD) and pneumonia diagnoses from five years prior to lung cancer diagnosis onward, and advanced or metastatic cancer stage.Results Patients with B cell deficiencies had a higher prevalence of comorbidities, including lung infections and COPD, compared to matched controls. Nevertheless, B cell deficiency was not associated with a significant difference in OS among patients treated with ICIs ( figure 1). Notably, among patients who did not receive ICIs, B cell deficiency was associated with improved OS (hazard ratio [0.45–0.80], P<0.001). Therapeutic B cell depletion was not associated with significant OS differences, irrespective of lung cancer treatment modality.Conclusions This retrospective analysis did not observe inferior OS among B cell-deficient NSCLC patients, even though they exhibited more comorbidities expected to increase mortality. A limitation of this study is that these outcomes may have been influenced by unmeasured confounding, such as differences in concomitant medications or healthcare utilization. Additionally, the extent of B cell levels reduction in our cohort is not precisely known, and likely represents partial rather than complete deficiency or depletion. Despite these limitations, our findings motivate continued investigation of the mechanistic role of B cells in anti-tumor immunity and the necessity of B cells for ICI benefit.Abstract 751 Figure 1OS in B cell-deficient patients compared to matched controls. (A) Hazard ratios and 95% CI for OS associated with health conditions, estimated from a multivariate Cox proportional hazards model stratified by matched set. (B) Kaplan-Meier curves for OS",
  "authors": [
    {
      "affiliations": [
        "Genentech, South San Francisco, CA, USA"
      ],
      "name": "Anna Obraztsova"
    },
    {
      "affiliations": [
        "F. Hoffmann-La Roche Ltd, Basel, Switzerland"
      ],
      "name": "Laura Perez"
    },
    {
      "affiliations": [
        "Genentech, South San Francisco, CA, USA"
      ],
      "name": "Meng Xiao He"
    }
  ],
  "title": "751 B cell deficiency or therapeutic depletion is not associated with impaired immunotherapy outcomes in NSCLC in real world data",
  "uid": "116406aa-85b9-57f6-ae0e-2528ef664417"
}