The University of Texas Health Science Center at Houston Houston, TX
Introduction: Immune checkpoint inhibitor (ICI) therapy has revolutionized cancer care and the management of advanced malignancies. Despite the efficacy of ICI therapy, this class of medications is often associated with immune-related adverse events (irAEs). Recent case reports have raised concern that acute appendicitis may be a possible irAE. Conventional appendicitis usually occurs in a younger population (age 5-45 years) and is characterized by acute right lower quadrant abdominal pain with a perforation rate of 20-30%. In this study, we aim to describe the disease course of appendicitis after ICI exposure and its associated complications.
Methods: We retrospectively studied adult patients who had an ICD code of appendicitis between their 1st dose of ICI and up to 2 years after during 01/2020-04/2021 and imaging evidence of appendicitis. Patients were excluded if the appendicitis diagnosis was prior to ICI exposure.
Results: Forty-four out of the 13,991 ICI patients had the ICD diagnostic code for appendicitis during the study period, among whom 10 patients met the inclusion criteria. The median age at the time of appendicitis diagnosis was 59 years (IQR=55-60). Seven patients (70%) were male. The most common malignancies were melanoma (n=4, 40%) and genitourinary cancers (n=3, 30%). Nine patients (90%) had stage IV cancer. Most patients received treatment with anti-PD-1/L1 monotherapy (60%). The median time from ICI initiation to appendicitis onset was 188 days (IQR=46-386). The median doses of ICI received was 4 (IQR=2-15). The most common presenting symptoms were abdominal pain (70%) and fever (40%). Abscess was present on imaging in two patients (20%) and a perforation was found in one patient (10%). No patients had symptoms or evidence of concurrent colitis. All ten patients had received antibiotic treatment. Five patients (50%) required surgical or IR intervention. Nine patients (90%) had resolution of appendicitis symptoms after treatment. Three patients (30%) had their ICI terminated after the episode of appendicitis.
Discussion: Appendicitis after ICI therapy is extremely rare. Compared to conventional appendicitis it occurs at an older age but with similar clinical presentations and comparable complication rates. Management strategies are comparable to conventional appendicitis, with appendectomy being the mainstay of treatment. Appropriateness of continuing ICI therapy after episode of appendicitis has yet to be delineated and is often determined by clinical judgement.
