Risk of Immune-Related Pancreatitis in Patients with Solid Tumors Treated with Immune Checkpoint Inhibitors: Systematic Assessment with Meta-Analysis

Su, Qiang; Zhang, Xiaochen; Zhang, Chenguang; Hou, Yanli; Yuxia, Yao; Cao, Bangwei

doi:10.1155/2018/1027323

Cited by 50 publications

(36 citation statements)

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“…The incidence of ICIPI in our cohort was 2% for anti-CTLA-4 monotherapy, 4% for anti-PD-1/L1 monotherapy, and 8% for combination therapy. Our findings corroborate those of a meta-analysis showing that the incidence of ICIPI was 0.9–3% in patients receiving anti-CTLA-4 monotherapy, 1.2–2.1% in patients receiving combination therapy of anti-CTLA-4 and anti-PD-1, and 0.5–1.6% in patients receiving anti-PD-1 monotherapy [22]. Freeman-Keller et al found that 1.35% of patients with resected and unresectable metastatic melanoma treated with nivolumab had asymptomatic grade 3 amylase/lipase elevation [30].…”

Section: Discussionsupporting

confidence: 90%

Clinical characteristics and outcomes of immune checkpoint inhibitor-induced pancreatic injury

Abu-Sbeih

Tang

Lü

et al. 2019

j. immunotherapy cancer

109

103

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BackgroundImmune checkpoint inhibitor (ICI)-induced pancreatic injury (ICIPI) is not well documented in the literature. We aimed to describe the clinical characteristics and outcomes of patients who developed ICIPI.MethodsWe reviewed the medical records of consecutive patients who had a confirmed diagnosis of ICIPI (Common Terminology Criteria for Adverse Events grade ≥ 3 lipase elevation with or without clinical symptoms) from April 2011 through April 2018.ResultsAmong the 2,279 patients received ICI and had lipase values checked thereafter, 82 (4%) developed ICIPI. Overall, 65% of patients received inhibitors of programmed death protein-1 or its ligand. Compared with asymptomatic presentation, patients who had clinical symptoms of pancreatitis (n = 32) had higher levels of lipase (P = 0.032), more frequent imaging evidence of pancreatitis (P = 0.055), and more frequent hospitalization (P < 0.001) and received intravenous fluids (P < 0.001) and steroids more frequently (P = 0.008). Twelve patients (15%) developed long-term adverse outcomes of ICIPI; three had chronic pancreatitis, four had recurrence of ICIPI, and six had subsequent diabetes. Among 35 patients who resumed ICI therapy, four (11%) had recurrence of lipase elevation. Logistic regression revealed that smoking and hyperlipidemia were associated with increased risk for long-term adverse outcomes of ICIPI, and intravenous fluids were associated with reduced risk. Patients who resumed ICI therapy survived longer than patients who discontinued ICI therapy permanently, statistically not significant (P = 0.0559). Patients who developed long-term adverse outcomes of ICIPI survived significantly longer than those who did not (P = 0.0295). The highest proportion of patients (6/21, 29%) developed long-term adverse outcomes of ICIPI was among those without typical symptoms of pancreatitis, continued ICI therapy after ICIPI, and did not receive intravenous fluids.ConclusionICIPI can present as typical acute pancreatitis, with risk of the development of a pseudocyst, diabetes, and chronic pancreatitis. ICI resumption after ICIPI may lead to recurrence of lipase elevation without increased risk of long-term adverse outcomes, and can increase survival duration. Intravenous fluids may prevent long-term adverse outcomes, but steroids do not appear to affect outcomes of ICIPI. Asymptomatic ICIPI presentation may lead to undertreatment of ICIPI owing to underestimation of its degree, and therefore, intravenous fluid administration could potentially could potentially be benificial to prevent long-term adverse outcomes even in asymptomatic patients.Electronic supplementary materialThe online version of this article (10.1186/s40425-019-0502-7) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 90%

Clinical characteristics and outcomes of immune checkpoint inhibitor-induced pancreatic injury

Abu-Sbeih

Tang

Lü

et al. 2019

j. immunotherapy cancer

109

103

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“…However, neither monotherapy nor combination therapy are seen to potentiate the risk of immune-induced pancreatitis. The precise and specific mechanism for such observed differences are still unknown [33]. Consistent with previous results of Wang et al, about 6% patients had grade 3 or higher colitis [34].…”

Section: Discussionsupporting

confidence: 81%

The safety and tolerability of combined immune checkpoint inhibitors (anti-PD-1/PD-L1 plus anti-CTLA-4): a systematic review and meta-analysis

Khadaroo

et al. 2019

BMC Cancer

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Background The future of combined immunotherapy (a PD-1/PD-L1 plus a CTLA-4 antagonist) is very bright. However, besides improving efficacy, combined therapy increases treatment-related adverse events (TRAEs). Also, the clinical application is limited in some solid tumors. Methods This paper purports to investigate the TRAEs for the combined immunotherapy aiming for a more appropriate utilization of immune checkpoint inhibitors (ICIs) in clinical practice through a meta-analysis. Results A total of 17 eligible studies covering 2626 patients were selected for a meta-analysis based on specified inclusion and exclusion criteria. The incidence rates of any grade and grade 3 or higher TRAEs were 88% (95%CI, 84–92%) and 41% (95%CI, 35–47%), respectively. The overall incidence of any grade TRAEs leading to discontinuation of treatment was 20% (95%CI, 16–24%). The incidence rate of treatment related deaths was 4.3‰ (95%CI, 1.4‰-8.4‰). Analysis showed that NIVO1 + IPI3 cohort had higher incidences of grade 3 or higher TRAEs (RR = 1.77, 95%CI, 1.34–2.34, p < 0.0001) and any grade TRAEs leading to discontinuation of treatment (RR = 1.81, 95%CI, 1.08–3.04, P = 0.02), compared with NIVO3 + IPI1 regimen. Conclusions The combined therapy had high TRAEs. The TRAEs, especially grade 3 or higher, led to discontinuation of the treatment. Furthermore, the incidence of treatment-related deaths was rare. Moreover, the NIVO3 + IPI1 regimen, regardless of efficacy, is more recommended because of better tolerance and lower adverse events. Electronic supplementary material The online version of this article (10.1186/s12885-019-5785-z) contains supplementary material, which is available to authorized users.

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“…On the other hand, pancreatitis caused irAE has been reported to occur in 0.9–3% for anti -CTLA-4 monotherapy, 1.2–2.1% for combination therapy of anti -CTLA-4 and anti -PD-1 and 0.5–1.6% for anti -PD-1 monotherapy according to a meta-analysis [ 10 ]. The incidence of the irAE pancreatitis caused by combination therapy of cytotoxic drugs and ICI was 0–1.4% [ [1] , [2] , [3] , [4] , [5] ].…”

Section: Discussionmentioning

confidence: 99%

A case of simultaneous occurrence of hepatitis and pancreatitis during the combination immunochemotherapy for non-small cell lung carcinoma

Tanaka

Asakawa

Komuta

et al. 2020

Respiratory Medicine Case Reports

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Immune checkpoint inhibitors (ICIs) improved the prognosis of patients with advanced lung cancers. The combination therapy of cytotoxic drugs and ICI is approved as first-line chemotherapy in non-small-cell lung cancer (NSCLC) and extensive disease small-cell lung cancer (ED-SCLC). It has been reported various immune-related adverse events (irAEs). We herein report a 65-year-old man with NSCLC who developed hepatitis and pancreatitis simultaneously during the combination immunochemotherapy. In the treatment of hepatitis and pancreatitis, the clinical course was different. In this report, the importance of accurate diagnosis through detailed examination and treatment priority depending on the severity of the symptoms is indicated.

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Risk of Immune-Related Pancreatitis in Patients with Solid Tumors Treated with Immune Checkpoint Inhibitors: Systematic Assessment with Meta-Analysis

Cited by 50 publications

References 36 publications

Clinical characteristics and outcomes of immune checkpoint inhibitor-induced pancreatic injury

Clinical characteristics and outcomes of immune checkpoint inhibitor-induced pancreatic injury

The safety and tolerability of combined immune checkpoint inhibitors (anti-PD-1/PD-L1 plus anti-CTLA-4): a systematic review and meta-analysis

A case of simultaneous occurrence of hepatitis and pancreatitis during the combination immunochemotherapy for non-small cell lung carcinoma

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