Author of

• 20156

  +

  P1.07 - Immunology and Immunotherapy (ID 693)

  • Event: WCLC 2017
  • Type: Poster Session with Presenters Present
  • Track: Immunology and Immunotherapy
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)

  • 22699

    +

    P1.07-031 - Autoantibodies Associated with Risk of Subclinical Autoimmunity and Immune-Related Adverse Events from Checkpoint Inhibitor Therapy (ID 10153)

    09:30 - 09:30  |  Author(s): Y.G. McCuthchen
    • Abstract

    Background:
    Immune checkpoint inhibitors have emerged as a highly promising treatment option for advanced lung cancer. However, a minority of patients develop unpredictable, potentially severe, and possibly permanent immune-related adverse events. We hypothesized that pre-existing subclinical autoimmunity predisposes patients to these toxicities.
    
    Method:
    We collected serum from patients treated with immune checkpoint inhibitors at multiple time-points: pre-treatment, 2-3 weeks, 6 weeks, 12 weeks, every 12 weeks thereafter, and at time of toxicity. We determined baseline and dynamic autoantibody profiles associated using an array panel of 125 antigens including nuclear, cytosolic, and tissue-specific antigens. Autoantibody levels between toxicity and no toxicity groups were compared using the quasi likelihood F test.
    
    Result:
    A total of 29 subjects were enrolled. Mean age was 69 years, 55% were women, and 83% had lung cancer. Immune-related adverse events occurred in 31% of cases as follows: pneumonitis (n=6), endocrinopathy (n=2), dermatitis (n=1). We also enrolled 11 healthy controls who underwent two blood draws 2-3 weeks apart. Across the entire cohort, there was substantial variation in baseline autoantibody levels. Patients receiving immunotherapy demonstrated a trend toward greater increase in autoantibody levels over time compared to the control group (P=0.23). In general, the greatest increases in autoantibody levels were noted among individuals with the highest baseline autoantibody levels. Broadly, elevated baseline levels of autoantibodies were associated with the development of immune-related adverse events, with 4 individual antibodies classically associated with systemic autoimmunity having significantly higher levels in the toxicity group (P<0.05). Immune-related adverse events were also more common among cases with greater post-treatment increase in antibody levels, with 10 individual antibodies having significant increases in the toxicity group (P<0.05).
    
    Conclusion:
    Subclinical autoimmunity occurs in a substantial proportion of patients with lung cancer and other malignancies. These clinically silent auto-antibodies may be associated with increased risk of immune-related adverse events from immune checkpoint inhibitor therapy.