Delayed hemorrhagic gastritis caused by immunotherapy in a patient With metastatic melanoma

Elmasry, Mohamed; Dong, Brian; Rios, Cristian D.; Breaux, Andrea; Miller, Donald

doi:10.1016/j.amjms.2022.02.010

Cited by 9 publications

(10 citation statements)

References 11 publications

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“…Although the instructions of pembrolizumab clearly pointed out that it has adverse reactions of bleeding, the mechanism is currently unclear. There are few reports in the literature that pembrolizumab may cause adverse effects related to bleeding disorders [14][15][16]18]. However, the study showed that hematuria was associated with a significantly higher risk of chronic kidney disease (CKD) progression and death in a large adult cohort with CKD [19].…”

Section: Discussionmentioning

confidence: 99%

“…It has been reported that pembrolizumab may also cause bleeding, including epistaxis, oral bleeding, gastric bleeding, and hematuria, but the incidence is low [14][15][16]. In addition, studies have shown that combination therapy will show a higher incidence of adverse events than single drugs, which may be due to different principles of adverse events caused by different drugs.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Severe hematuria in a patient receiving bevacizumab and pembrolizumab for metastatic cervical cancer: a case report

Liu

Dong²,

et al. 2023

BMC Nephrol

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Background Bevacizumab is a monoclonal antibody drug targeting Vascular Endothelial Growth Factor (VEGF), which binds to VEGF receptors to inhibit vascular endothelial cell proliferation and angiogenesis, thus inhibiting tumorigenesis. Pembrolizumab is a monoclonal antibody that can bind to the programmed death-1 (PD-1) receptor, which can block the binding of the PD-1 receptor to its ligands PD-L1 and PD-L2, and release PD-1 pathway-mediated suppression of immune responses. By blocking the activity of PD-1, the purpose of inhibiting tumor growth is achieved. Case presentation We report a severe hematuria of bevacizumab plus pembrolizumab, in a 58-year-old woman with metastatic cervical cancer. After three cycles every three weeks of consolidation chemotherapy (carboplatin, paclitaxel, bevacizumab) and following three cycles consolidation chemotherapy (carboplatin, paclitaxel, bevacizumab, pembrolizumab), the patient presented a worsening state. Manifested as massive gross hematuria with blood clots. After stopping chemotherapy, cefoxitin, tranexamic acid and hemocoagulase atrox therapy was administered resulting in rapid clinical improvement. The patient was a cervical cancer with bladder metastasis that increases the risk of development of hematuria. Inhibition of VEGF, which has anti-apoptotic, anti-inflammatory, and pro-survival influences on endothelial cells, weakens their regenerative capacity and increases expression of proinflammatory genes leading to weakened supporting layers of blood vessels and, hence, to damaged vascular integrity. In our patient, the development of hematuria may result from the anti-VEGF effect of bevacizumab. In addition, pembrolizumab may also cause bleeding, and the mechanism of bleeding caused by pembrolizumab is currently unclear, which may be related to immune mediation. Conclusion To our knowledge, this is the first case reporting on the development of severe hematuria during bevacizumab plus pembrolizumab treatment, which should alert the clinicians in case of bleeding adverse events onset in older patients under bevacizumab plus pembrolizumab therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Severe hematuria in a patient receiving bevacizumab and pembrolizumab for metastatic cervical cancer: a case report

Liu

Dong²,

et al. 2023

BMC Nephrol

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“…2 Although ICI-mediated gastritis has been reported in the literature, hemorrhagic complication due to this entity is extremely rare because it is seen in only a handful of cases. [4][5][6]8,9 IrAEs related to ICIs are typically organ-specific, and onset in some cases may be delayed by months. 10 IrAEs related to anti-PD-1 antibodies (such as nivolumab and pembrolizumab) differ in frequency and organ involvement compared with other ICIs, and observed complications may be more severe.…”

Section: Discussionmentioning

confidence: 99%

“…13 We reviewed 6 other case reports with ICI-induced hemorrhagic gastritis, of which 3 were associated with pembrolizumab monotherapy, 1 with nivolumab monotherapy, 1 with ipilimumab monotherapy, and 1 with ipilimumab and nivolumab combination therapy. [4][5][6]8,9,14 ICIs act on the modulation of T-cell response to the antigen. After activation of T cells through antigen recognition and costimulation, PD-1 expression is induced.…”

Section: Discussionmentioning

confidence: 99%

Immune Checkpoint Inhibitor-Induced Hemorrhagic Gastritis

Mathialagan,

Tai,

Sethi

et al. 2023

ACG Case Rep J

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Immune checkpoint inhibitors (ICIs) have been increasingly used in the treatment of several malignancies and may target cytotoxic T-lymphocyte-associated antigen-4, programmed cell death-1, and programmed cell death ligand 1, which work on maintaining peripheral immune tolerance. ICIs inhibit these ligands causing an immune-enhancing effect, leading to a wide spectrum of complications from mild mucositis to life-threatening pneumonitis or hepatitis. These complications are collectively called immune-related adverse events. Their prevalence has increased with a rise in ICI use, with rare manifestations being reported in popular literature. We present a case of hemorrhagic gastritis due to the anti-programmed cell death-1 antibody, pembrolizumab.

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“…The corticosteroid tapering schedule for these irAEs has not been established. However, tapering corticosteroid should be done cautiously because it was reported that histopathological findings still showed residual inflammation despite an improvement in the patients’ symptoms and in the imaging findings after three months of corticosteroid treatment [ 17 , 18 ]. Moreover, in the previous case, combined immunosuppressive therapy with PSL, mycophenolate mofetil and tacrolimus did not improve cholangitis and the patient died of liver failure [ 16 ].…”

Section: Discussionmentioning

confidence: 99%

Concurrent Nivolumab-Induced Gastritis and Cholangitis Accompanied by Biliary Tract Hemorrhage in a Patient With Stage IV Lung Adenocarcinoma

Tsukaguchi,

Yamaguchi,

Ogawa

et al. 2023

Cureus

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Immune checkpoint inhibitors, including nivolumab, can result in immune-related adverse events (irAEs) that may affect multiple organ systems. Among irAEs, both gastritis and cholangitis are uncommon. We present the case of a 65-year-old man who received nivolumab for lung adenocarcinoma presented with epigastric pain. He was diagnosed with immune-related gastritis and cholangitis based on imaging and pathological findings. We administered prednisolone (1 mg/kg/day), which improved the patient’s gastritis and relieved his pain. However, he experienced recurrent epigastric pain during corticosteroid tapering, and magnetic resonance imaging showed biliary tract hemorrhage. After watchful waiting, the hemorrhage improved without additional immunosuppressants. Immune-related gastritis, immune-related cholangitis, and their coexistence should be considered in patients who develop epigastric pain during immune checkpoint inhibitor therapy. When patients with concurrent immune-related gastritis and cholangitis complain of recurrent epigastric pain, it is important to assess which of these two irAEs is worsening because the optimal immunosuppressants differ between the two.

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Delayed hemorrhagic gastritis caused by immunotherapy in a patient With metastatic melanoma

Cited by 9 publications

References 11 publications

Severe hematuria in a patient receiving bevacizumab and pembrolizumab for metastatic cervical cancer: a case report

Severe hematuria in a patient receiving bevacizumab and pembrolizumab for metastatic cervical cancer: a case report

Immune Checkpoint Inhibitor-Induced Hemorrhagic Gastritis

Concurrent Nivolumab-Induced Gastritis and Cholangitis Accompanied by Biliary Tract Hemorrhage in a Patient With Stage IV Lung Adenocarcinoma

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