Immune Checkpoint Inhibitor-Induced Pancreatic Injury (ICI-PI) in Adult Cancer Patients: A Systematic Review and Meta-Analysis

Abstract

Background: Immune checkpoint inhibitor-induced pancreatic injury (ICI-PI) is a rare immunotoxicity, with limited data on treatment and long-term outcomes. Methods: PubMed, EMBASE, and Cochrane Library were systematically searched for studies reporting ICI-PI in patients with solid malignancies. ICI-PI was defined as pancreatic inflammation post-ICI exposure, diagnosed via radiologic changes or elevated lipase/amylase levels without other underlying causes. The CTCAE grading system was used. The primary objectives were to assess the frequency, severity, serum abnormalities, management, and long-term outcomes. We conducted a proportional single-arm meta-analysis with a random effects model. Results: The analysis included 25 retrospective studies involving 48,704 patients. Tumor types included thoracic/head and neck (38%), skin (26%), genitourinary/gynecological (18%), gastrointestinal (12%), and others (6%). The median age ranged from 56 to 73 years, with a follow-up from 2.5 to 45.9 months. ICI-PI occurred in 3.60% (95% CI: 1.64–6.28%) of patients, with grade ≥ 3 toxicity in 59.45% (95% CI: 35.32–81.37%). The frequency rates of ICI-PI were 1.99% for CTLA4 inhibitors, 5.01% for PD(L)1 inhibitors, and 7.44% for combination ICI therapy (p < 0.01). The median time to onset from treatment initiation ranged from 30 to 390 days, and symptom resolution ranged from 55 to 84 days. Management included corticosteroids (30.20%), intravenous fluids (22.82%), and hospitalization (30.46%). Chronic complications affected 63.54% (95% CI: 29.03–91.56%), including primarily diabetes mellitus (DM 89.45%; 95% CI: 61.88–100.0%) and exocrine pancreatic insufficiency (EPI 10.55%; 95%: 0.0–38.12%). ICI-PI recurrence occurred in 27.2% of those resuming ICI therapy. The objective response rate was 61.7% (95% CI: 55.08–68.17%). Conclusions: ICI-PI, though infrequent, is severe and predisposes patients to chronic complications, including DM and EPI.