Rapid Fire Best of the Best Poster Oral Clinical Oncology Society of Australia Annual Scientific Meeting 2021

Antibiotic Use, Clinical Outcomes, and Systemic Immune Biomarkers in Patients Receiving Immune Checkpoint Inhibitor Therapy (#324)

Mitchell S von Itzstein 1 2 , Amrit S Gonugunta 3 , Thomas Sheffield 4 , Jade Homsi 1 , Jonathan E Dowell 1 , Andrew Y Koh 5 , Prithvi Raj 6 , Farjana Fattah 2 , Vijay S Basava 2 , Jason Y Park 7 , Vinita Popat 3 , Jessica M Saltarski 2 , Yvonne Gloria-McCutchen 2 , David Hsiehchen 1 , Jared Ostmeyer 4 , Shaheen Khan 6 , Yang Xie 4 , Quan-Zhen Li 6 , Edward K Wakeland 6 , David E Gerber 1 2 4
  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. School of Medicine, UT Southwestern Medical Center, Dallas, TX, United States
  4. Population and Data Sciences, UT Southwestern Medical Center, Dallas, TX, United States
  5. Department of Pediatrics, UT Southwestern Medical Center, Dallas, TX, United States
  6. Department of Immunology, UT Southwestern Medical Center, Dallas, TX, United States
  7. Department of Pathology , UT Southwestern Medical Center, Dallas, TX, United States

Background: Antibiotics are associated with worse clinical outcomes in patients receiving immune checkpoint inhibitors (ICI). While antibiotics are known to affect the gut microbiome, effects on systemic immune markers are unknown. We therefore evaluated the effects of antibiotics on systemic immune parameters in a cohort of patients receiving ICI.

 

Methods: We identified antibiotic exposure (6 weeks before to 6 weeks after ICI initiation) and clinical outcomes for 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 markers, P <0.05 and false discovery rate (FDR) <0.2 were considered significant.

 

Results: A total of 254 patients were included in the cohort, of whom 138 (54%) received antibiotics. Patients who received antibiotics had worse clinical outcomes: median overall survival (OS) 297 vs. 546 days (HR 1.69; 95% CI, 1.22-2.35; P=0.002); median progression-free survival (PFS) 154 vs. 305 days (HR 1.69; 95% CI, 1.07-2.06; P=0.02); radiographic response (P=0.05). Antibiotic use after ICI initiation was associated with the worst outcomes: median OS 187 vs. 550 days (HR 2.19; 95% CI, 1.58-3.04; P<0.001); median PFS 121 vs. 321 days (HR 1.83; 95% CI, 1.3-2.56; P<0.001). There were no differences in cytokine levels according to antibiotic exposure. Patients who received antibiotics prior to ICI initiation had lower levels of nucleolin, c-reactive protein, and MDA5 autoantibodies (all FDR 0.17), and higher levels of heparin sulfate autoantibodies (FDR 0.18) at ICI initiation. Six weeks after ICI initiation, antibiotic-exposed patients had lower levels of MDA5, CENP.B, and nucleolin autoantibodies (all FDR 0.05).

 

Conclusions: Antibiotics are associated with worse clinical outcomes with ICI. Antibiotic exposure was associated with modest differences in systemic immune parameters. Further research into the effects of antibiotics on immune function is warranted.