P1883 - An Alternative Treatment Regimen in Chronic Pembrolizumab Use Induced Autoimmune Hepatitis

Atul Sinha, MD, Deepthi Kagolanu, MD, Nausheer Khan, MD, Kaleem Rizvon, MD
Nassau University Medical Center, East Meadow, NY

Introduction: Pembrolizumab is a monoclonal programmed death receptor-1 (PD-1)-blocking antibody used in the treatment of various cancers. Immune mediated hepatitis is a rare but serious adverse effect that occurs in 0.7% of patients receiving pembrolizumab therapy with median time of onset of 1.3 months. Despite the rarity and established timeline, clinicians should be cognizant of adverse events that may not follow the usual chronological patterns and be prepared to intervene to prevent further severity of treatment related complications.

Case Description/Methods: A 66-year-old female with history of stage IV non-small cell adenocarcinoma of the lung was admitted for asymptomatic transaminitis. ALT and AST were greater than 20 times the upper limit of normal. Patient had already received 15 cycles of intravenous pembrolizumab over the previous 16 months, last received 4 weeks prior to admission. She was diagnosed with grade 4 hepatitis (Table 1) and was started on methylprednisolone with the addition of mycophenolate mofetil (MMF) after 7 days due to worsening transaminases, as per guidelines. IV steroid tapering and de-escalation to oral steroids began while patient was in grade 3 hepatitis. She was discharged on oral prednisone and MMF, both of which were tapered and discontinued as transaminitis resolved.

Discussion: Our case is unique due to the delayed onset of pembrolizumab induced grade 4 autoimmune hepatitis along with a modified approach of accelerated steroid taper due to treatment related complication. We followed ASCO and ESMO guidelines with initial treatment of IV steroids for grade 4 hepatitis. Guidelines suggest beginning taper once hepatitis improves to grade 2 or less but guidelines were not strictly followed in part because hospital course was complicated by labile diabetes. Instead, steroid taper began once liver enzymes were consistently decreasing to decrease the patient’s insulin requirements. We have demonstrated that a patient with grade 4 hepatitis can safely begin steroid tapering while in grade 3 hepatitis, as opposed to the lower grades that guidelines suggest, with the use of steroid sparing agents. This is important for clinicians hoping to avoid or minimize the many side-effects of corticosteroids while treating the complications of PD-1 inhibitors.

1. V5. Common terminology criteria for adverse events (CTCAE) [Internet]. Cancer.gov. [cited 2021 Apr 26]. Available from: https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/ctcae_v5_quick_reference_5x7.pdf

Hepatitis Grade	Criteria
Grade 1	Asymptomatic (AST or ALT > ULN to 3.0 × ULN and/or total bilirubin > ULN to 1.5 × ULN)
Grade 2	Asymptomatic (AST or ALT > 3.0 to ≤ 5 × ULN and/or total bilirubin > 1.5 to ≤ 3 × ULN)
Grade 3	Symptomatic liver dysfunction, fibrosis by biopsy, compensated cirrhosis, reactivation of chronic hepatitis (AST or ALT 5–20 × ULN and/or total bilirubin 3–10 × ULN)
Grade 4	Decompensated liver function (eg, ascites, coagulopathy, encephalopathy, coma; AST or ALT > 20 × ULN and/or total bilirubin > 10 × ULN)

Table: Table 1: Immune Checkpoint Inhibitor Induced Autoimmune Hepatitis Grading.[1]


ULNf upper limit of normal
ALT= alanine aminotransferase
AST= aspartate aminotransferase


Disclosures:
Atul Sinha indicated no relevant financial relationships.
Deepthi Kagolanu indicated no relevant financial relationships.
Nausheer Khan indicated no relevant financial relationships.
Kaleem Rizvon indicated no relevant financial relationships.


Atul Sinha, MD, Deepthi Kagolanu, MD, Nausheer Khan, MD, Kaleem Rizvon, MD. P1883 - An Alternative Treatment Regimen in Chronic Pembrolizumab Use Induced Autoimmune Hepatitis, ACG 2021 Annual Scientific Meeting Abstracts. Las Vegas, Nevada: American College of Gastroenterology.