Immune checkpoint inhibitor-induced pancreatic enzyme elevation in melanoma patients: Incidence, management and therapy-A multicentre analysis.

Background: Immune checkpoint inhibitors (ICI) are considered standard-of-care in the systemic treatment of melanoma. However, management of certain ICI-associated adverse events (AE) can be challenging. Incidence, course and management of immune checkpoint inhibitor-induced pancreatic injury (ICIPI) are not well-documented and specific diagnostic and therapeutic algorithms are lacking. Current management includes serological monitoring of pancreatic enzymes, radiographic imaging and corticosteroid or further immunosuppressive treatment.

Objectives: Based on previous data regarding adjuvant ICI treatment, we suspected that elevation of pancreatic enzymes may occur more frequently than reported while the clinical relevance of-particularly asymptomatic-ICIPI is still unclear.

Methods: A collaboration of eight Austrian and Swiss dermato-oncology centres was established to retrospectively analyse a large cohort of ICI-treated patients regarding incidence and management of ICIPI. Additionally, a questionnaire-based survey concerning ICIPI-management was conducted.

Results: Among 1516 melanoma patients receiving ICI therapy, 204 patients exhibited ≥CTCAE II° lipase elevation. Of these patients, 41 (20.1%) had symptoms suggestive of pancreatitis. Immunotherapy was interrupted or discontinued due to pancreatic AE in almost half of the patients. Systemic corticosteroids were administered in 103 patients (50.5%), with higher doses reported in symptomatic cases. Six per cent of asymptomatic patients had radiographically proven pancreatitis. Maximum lipase elevation was >5xULN in all of these patients.

Conclusion: Routine lipase monitoring was conducted in all participating centres, although not recommended in respective guidelines. Elevation of serum lipase was observed more frequently than recently reported. Although radiographic findings indicating pancreatitis were rare in asymptomatic patients, ICI treatment was frequently paused or discontinued and systemic steroids were administered. To reduce the existing uncertainty in routine clinical practice reflected by our findings, we provide an algorithm to guide the monitoring and management of potential pancreatic adverse events. Lipase measurement should be limited to symptomatic patients and/or those with radiographic findings indicative of pancreatic injury.