Oral Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2021

Clinical and biological correlates of immune-related adverse events (#96)

Mitchell S von Itzstein 1 2 , Thomas Sheffield 3 , Michael C Burke 1 , David Hsiehchen 1 , Farjana Fattah 2 , Hong Mu-Mosley 2 , Jason Y Park 4 , Shaheen Khan 5 , Jared Ostmeyer 3 , Jonathan E Dowell 1 , Jade Homsi 1 , Jessica M Saltarski 2 , Yvonne Gloria-McCutchen 2 , Yang Xie 3 , Quan-Zhen Li 5 , Edward K Wakeland 5 , David E Gerber 1 2 3
  1. Department of Medicine/Division of Oncology, UT Southwestern Medical Center, Dallas, TX, United States
  2. Harold C Simmons Cancer Center, UT Southwestern Medical Center, Dallas, TX, United States
  3. Population and Data Sciences, UT Southwestern Medical Center, Dallas, TX, United States
  4. Department of Pathology , UT Southwestern Medical Center, Dallas, TX, United States
  5. Department of Immunology, UT Southwestern Medical Center, Dallas, TX, United States

Introduction: Immune checkpoint inhibitors (ICI) have revolutionised modern cancer treatment. However, they may cause toxicities known as immune-related adverse events (irAE), which are unpredictable and potentially severe. We therefore evaluated systemic immune markers, cytokines and antibodies, in a cohort of patients receiving ICI.

 

Methods: We identified clinical outcomes including overall survival (OS) and development of irAE in a cohort of patients enrolled in a prospective biospecimen collection protocol. Multiplex panels of 40 serum cytokines and 124 serum autoantibodies at baseline and 6 weeks after ICI initiation were analyzed. For differences in immune parameters, P <0.05 and false discovery rate (FDR) <0.2 were considered significant.

 

Results: A total of 327 patients were included in the cohort, of whom 205 (63%) developed an irAE. Development of irAE was associated with improved OS (HR 0.67; 95% CI, 0.49-0.93; P=0.015). In multivariate models, grade 1 irAE were associated with improved OS with HR 0.63 (95% CI 0.45-0.89; P<0.01). Dermatological irAEs (HR 0.58; P=0.012) and hyperthyroidism (HR 0.40; P=0.013) were also associated with improved OS. Levels of several cytokines were reduced at baseline (CXCL8, CXCL9, CXCL10, CCL20, IL-4, CXCL13, interferon-gamma, and CCL1; all P<0.05 and FDR<0.2) and increased at 6 weeks (CXCL10; FDR=0.1) in those that developed an irAE. Levels of cytokines between different irAE grades were similar.

 

Conclusions: Development of an irAE is associated with improved outcomes, with strongest correlation noted for grade 1, dermatological, and thyroid irAE. A characteristic pattern of dynamic changes including lower baseline levels of interferon gamma-inducible cytokines and greater increases in CXCL10 at 6 weeks is associated with development of irAE, regardless of irAE grade.