Scientific Poster Session II - Original Research

Original Research
  Sunday, November 12, 2023
  12:45 PM–02:15 PM

Abstract

Introduction:

Pembrolizumab, an immune checkpoint inhibitor, was approved in 2014. It was studied at 200mg every three-weeks(Q3W) versus 400mg every six-weeks(Q6W). The Food and Drug Administration granted accelerated approval of 400mg-Q6W in 2020. Our 2021 study found both 200mg-Q3W or 400mg-Q6W was well-tolerated. We noted Q6W arm led to liver inflammation and faster onset of hepatotoxicity. Current published literature does not address management of changes in liver function tests(LFTs).

Research Question or Hypothesis:

Are there risk factors that lead to a rise in LFTs with Pembrolizumab Q6W regimens?

Study Design: Retrospective two-year study in patients with increased LFTs on Q6W-regimen.Two arms: GroupA-dosing and hepatotoxicity, GroupB-hepatotoxicity risk factors across a 5-hospital system.

Methods:

Patients included if they received one dose of pembrolizumab 200mg or 400mg with a rise in AST, ALT or bilirubin. Patients excluded for concomitant chemotherapy, oral anticancer agent or switched dosing frequency more than once.Demographic information, pembrolizumab indication, GroupA’s baseline LFTS and GroupB’s hepatotoxic risk factors analyzed. Numeric variables summarized as medians and interquartile ranges(IQR) by Mann-Whitney U Test. Categorical variables summarized as frequencies and compared by Chi-square, or Fisher-exact tests. All statistical differences considered significant if p<0.05.The Charlson Comorbidity Index(CCI) predicts patient mortality utilizing chronic conditions;Age-Adjusted Charlson Comorbidity Index (ACI)Score is modified from CCI Score.

Results:

Study evaluated 388 patients. Baseline characteristics and LFTs similar in non-hepatotoxic and hepatotoxic groups.Hepatoxicity noted in 22 patients on pembrolizumab monotherapy and compared to 30 non-hepatotoxic patients. GroupA showed higher rates of hepatotoxicity in the Q3W group.GroupB showed hepatotoxic patients had higher ACI scores and liver abnormality on imaging(p<0.05).

Conclusion:

Liver toxicity rates were similar between Q3W and Q6W patients. Patients with higher ACI scores and liver abnormalities were more likely to experience liver toxicity. Overall, no significant difference in liver toxicity or risk factors was noted between the Q3W and Q6W-groups.This is the first study to evaluate this safety signal.

Presenting Author

Harminder Sikand Pharm.D., FCSHP, FASHP, FCCP
Scripps Mercy Hospital

Authors

Inderpreet Bhatti DO
Scipps Mercy Hospital

Kathryn Bollin MD
Scripps Mercy Hospital

Yuri Kim PharmD
Scripps Mercy Hospital

John Garrett Pharm D.
Scripps Mercy Hospital

David Savage MD, PhD
Scripps Clinc