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Pancreatic adverse events in patients treated with immune checkpoint inhibitors
Caroline Hana1, Tauseef Rehman1, Kyeeun Park1
1Memorial Healthcare System Pembroke Pines Florida USA.
Background And Aim:
The inhibition of cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) and programmed cell death-1 (PD-1) has been a target for multiple drugs to enhance the T-cell antitumor activity. However, these immune checkpoint inhibitors (ICIs) come with a panel of immune-related adverse events (irAEs) that include mainly endocrine, skin, and gastrointestinal effects. We report seven cases of pancreatic irAEs in patients treated with ICIs at our institute.
Methods:
This is a case series; data was collected through chart review by 3 different data collectors and was analyzed separately by 2 physicians.
Results:
Of these seven cases, two had diabetic ketoacidosis (DKA), while five had pancreatitis diagnosed by a substantial rise in serum lipase. Pancreatitis was asymptomatic in two cases. A pancreatic biopsy in one case revealed type 2 autoimmune pancreatitis. The ICIs used included pembrolizumab, nivolumab, durvalumab, and avelumab. Treatment included steroids and holding the ICI therapy: three cases had complete resolution of pancreatitis while two cases required either a prolonged taper or a second course of prednisone for recurrence of pancreatitis. On the other hand, the DKA cases were treated with withdrawal of the ICI and starting insulin with no steroid therapy.
Conclusions:
Pancreatitis and DKA are rare adverse events of ICIs that can be controlled by holding the ICI with or without starting steroids. Rechallenging the patient with the same ICI is possible in selected cases.
Insights
Immune checkpoint inhibitors (ICIs) targeting CTLA-4 and PD-1 can cause rare pancreatic adverse events like pancreatitis and diabetic ketoacidosis (DKA). Management involves holding ICI therapy, with steroids for pancreatitis and insulin for DKA, showing potential for ICI rechallenge.
Area of Science:
- Oncology
- Immunology
- Gastroenterology
Background:
- Immune checkpoint inhibitors (ICIs) targeting cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) and programmed cell death-1 (PD-1) enhance anti-tumor T-cell activity.
- However, ICIs are associated with immune-related adverse events (irAEs), predominantly affecting endocrine, skin, and gastrointestinal systems.
Purpose of the Study:
- To report and characterize rare cases of pancreatic irAEs in patients receiving ICIs.
- To describe the clinical presentation, management, and outcomes of these pancreatic irAEs.
Main Methods:
- A case series was conducted, involving chart review of seven patients who developed pancreatic irAEs.
- Data were collected by three data collectors and analyzed by two physicians.
Main Results:
- Seven cases of pancreatic irAEs were identified, including two cases of diabetic ketoacidosis (DKA) and five cases of pancreatitis.
- Pancreatitis was diagnosed via elevated serum lipase, with one case confirmed as autoimmune pancreatitis by biopsy. Two pancreatitis cases were asymptomatic.
- Treatment involved ICI discontinuation and/or steroids for pancreatitis, and ICI withdrawal with insulin for DKA. Three pancreatitis cases resolved completely, while two experienced recurrence.
Conclusions:
- Pancreatitis and DKA are rare but significant irAEs associated with ICI therapy.
- Management strategies include ICI cessation and supportive care (steroids for pancreatitis, insulin for DKA).
- Rechallenging patients with ICIs may be feasible in select cases following resolution of pancreatic irAEs.
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