Case Presentation: A 96-year-old male with a history of type 2 diabetes mellitus, hypertension, coronary artery disease, and recurrent skin malignancies (melanoma and squamous cell carcinoma) presented with acute epigastric abdominal pain radiating to the back accompanied by nausea and anorexia. He had two previous episodes of similar presentation at another healthcare facility. His recent medical history included starting immunotherapy with Pembrolizumab for recurrent metastatic melanoma of the scalp, with a new hepatic lesion noted on a recent PET–CT scan. His first episode of pancreatitis occurred two weeks after initiating therapy; no clear etiology was found after initial laboratory and imaging was done. For concern of immune-related adverse events (IrAE), immunotherapy was delayed for a month and restarted after being asymptomatic for almost four weeks. After receiving four cycles of Pembrolizumab, he had his second episode of pancreatitis, and immunotherapy was stopped for the second time. His third episode happened after discontinuing therapy for two months. This time, laboratory workup revealed a lipase level in the 800s. CT of the abdomen and pelvis ruled out pseudocysts or complications of pancreatitis, while ultrasound showed mild gallbladder sludge without biliary duct dilation. After supportive measures, the patient resumed diet with no recurrence of pain. Surgery was consulted, which did not recommend any surgical intervention considering the patient’s age and the low likelihood that his episodes of pancreatitis were caused by biliary disease. Immunotherapy was halted indefinitely by his oncologist due to recurrent pancreatitis.
Discussion: As clinicians, we frequently encounter pancreatitis in our daily practice. Pembrolizumab-induced pancreatitis is becoming increasingly prevalent as immune checkpoint inhibitors (ICI) are increasingly employed to treat various types of cancer. According to our literature search, the incidence of pancreatitis related to immune checkpoint inhibitors (ICI) is rare, with a report of less than 1% and it is actually associated with combination therapy of CTL-4 and PD-1 agents (1), but our case shows a single agent is enough to cause pancreatitis. Regarding treatment, management still depends on the severity but generally includes discontinuation of ICI and systemic steroids. (3) However, our patient did not receive steroids and was treated successfully with supportive care; other studies showed that there is no value of steroids in the management of pancreatitis, nor did it prevent short or long-term adverse effects. (4) Lastly, the literature describes some patients who are at increased risk of IrAEs – like patients with autoimmune disease or even advanced age. (5) A recent meta-analysis showed that the benefit of treatment did not appear to be dependent on age, and even carefully selected patients older than 90 years of age were safely treated. (5) Unfortunately, in most trials, elder adults are underrepresented.
Conclusions: Immune checkpoint inhibitors have revolutionized cancer treatment and are used in multiple types of cancers, including metastatic melanoma. Although IRAEs are rare, as clinicians, we have to be aware of the variety of adverse events, including their risk of morbidity and mortality, to make appropriate decisions for our patients. Our case also emphasizes the need for metanalysis with the inclusion of all types of patient populations to make final decisions on the safety profile of these medications.