Colorectal cancer (CRC) is the third leading cause of mortality worldwide. The Food and Drug Administration recently designated pembrolizumab, an immune checkpoint inhibitor (ICI) against a programmed death-1 receptor, as a breakthrough drug for the treatment of patients with mCRC whose tumors have deficient mismatch-repair gene expression (as evidenced by microsatellite instability-high) and patients with solid tumors with a high tumor mutational burden with ≥10 mutations/megabase. We present a patient with metastatic CRC having renal and adrenal gland metastases. Comprehensive molecular profiling performed on a site of metastatic CRC in the kidney revealed multiple genomic alterations characteristic of CRC and rare chromosome 9p24.1 amplification, resulting in a co-amplification of the PDL1, PDL2, and JAK2 genes. Although this genomic alteration may predict the response to ICI, the lack of pembrolizumab prevented the patient from receiving targeted treatment and succumbing to the disease.

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BACKGROUND: Immune checkpoint inhibitors (ICIs) are a new class of antitumor drugs that have been approved to treat a variety of malignant tumors. However, the occurrence of immune related adverse events (irAEs) has become an important reason for terminating treatment. ICIs sometimes lead to diarrhea and colitis, with severe enterocolitis potentially causing the hemorrhage of the lower gastrointestinal tract and colonic perforation. ICI-associated colitis is primarily treated with glucorticosteroids and/or agents targeting tumor necrosis factor-α. Here, we describe a case of severe ICI-associated colitis due to anti-programmed cell death ligand 1 (PD-L1) (durvalumab) treatment for small cell lung cancer with liver metastasis. The patient exhibited a poor response to rescuable therapy, and eventually received a laparoscopic subtotal colectomy and ileostomy. The data presented here will contribute to optimizing current treatment strategies for patients with severe ICI-associated colitis.
METHODS: A 71-year-old man was admitted for a second course of anti-PD-L1 + IP (durvalumab + irinotecan + cisplatin) treatment to manage lung cancer with liver metastasis, diagnosed 1 mo previously. Four days after the second dose, the patient developed abdominal pain and bloody diarrhea. Due to the anti-PD-L1 medication history and colonoscopy findings of the patient, he was diagnosed with a colitis associated with ICI treatment. After treatment with sufficient glucocorticoids and two courses of infliximab, the patient developed severe lower gastrointestinal bleeding. After adequate assessment, the patient was treated by laparoscopic surgery, and was discharged in stable condition.
CONCLUSIONS: The early screening and hierarchical management of irAEs need the joint participation of a multidisciplinary team. For ICI-related colitis with ineffective medical treatment, timely surgical intervention could prevent the death of patients.

Immune checkpoint inhibitor (ICI)-induced colitis is one of the known complications of therapies targeting cytotoxic programmed cell death protein 1 (PD-1), cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), and programmed cell death ligand 1 (PD-L1). ICI-associated colitis is routinely treated with immunosuppressive therapy, including corticosteroids and/or agents targeting tumor necrosis factor-α (TNF-α). In this report, a 69-year-old male patient developed severe ICI-induced colitis 2 weeks after anti-PD-L1 mAb (i.e., durvalumab) treatment; unexpectedly failed to respond to systemic corticosteroid, anti-TNF, and anti-integrin agents; and unfortunately died in 1 month. This case reminds clinical physicians to be on the alert for early-onset acute ICI-induced colitis and emphasizes that urgent optimized rescue measures are required for patients with severe ICI-induced colitis.

Our pathological study of a case of poorly differentiated lymphocyte-rich hepatocellular carcinoma suggested that immune checkpoint inhibitor may be an effective therapy. The histological type is an important factor in determining treatment choices.

The patient was an 80-year-old woman with combined pulmonary fibrosis and emphysema. She was diagnosed with pulmonary pleomorphic carcinoma in the right upper lobe, which relapsed 18 months after the operation. Computed tomography showed a mass in contact with the posterior wall of the lower part of the stomach. The patient was treated with two cycles of pembrolizumab, but the disease progressed. She was treated with S-1 as second-line therapy, resulting in tumor-shrinking after two cycles. Progression was not observed over the next twelve months. We report a rare case involving S-1 after immune checkpoint inhibitor treatment.

BACKGROUND: Recurrent hepatocellular carcinoma (HCC) with inferior vena cava tumor thrombus is a great challenge for oncologists and has a poor prognosis. To date, the safety and efficacy of programmed cell death ligand 1 (PD-L1) inhibitors are still unknown.
METHODS: A 59-year-old male was identified as having a tumor thrombus in the inferior vena cava 3 years after surgery. The patient underwent a second surgery and adjuvant chemotherapy. However, the level of alpha-fetoprotein was elevated after 2 mo, and lung metastases and mediastinal lymph node metastases were identified. The expression of PD-L1 in HCC and inferior vena cava tumor thrombus tissues was analyzed by immunohistochemistry. Then, the patient received atezolizumab immunotherapy. The level of alpha-fetoprotein dropped to normal, the mediastinal lymph node metastases decreased in size and the lung metastases disappeared after 3 mo of immunotherapy. The patient had no signs of recurrence at 21 mo of follow-up. A 60-year-old male underwent left hepatic tumor resection, inferior vena cava incision and thrombus removal, followed by regular chemotherapy. The patient developed lung and splenic metastases after surgery. Pembrolizumab was used for six courses, and the splenic metastasis shrank, after which splenectomy was performed. The patient continued to receive pembrolizumab for thirteen courses, and the lung metastases showed no progression. A 34-year-old male was diagnosed with liver cancer with inferior vena cava tumor thrombus. The patient underwent right hepatectomy and received tislelizumab for three courses. He is still receiving immunotherapy and in good condition.
CONCLUSIONS: Anti-PD-L1 therapy in HCC patients with inferior vena cava tumor thrombus and metastasis is associated with relatively good patient outcomes.

Immune checkpoint blockade with programmed cell death protein-1 (PD-1)/programmed cell death ligand-1 (PD-L1) inhibitors has been standard care for metastatic nonsmall cell lung cancer (NSCLC) and after progression using first-line platinum-containing chemotherapy. Although several management guidelines exist for immune checkpoint inhibitor-induced toxicities, uncommon, complicated, and life-threatening immune-related adverse events remain challenging for oncologists. In this report, we presented a male patient with NSCLC who received pembrolizumab during disease progression. He developed interstitial pembrolizumab-induced organizing pneumonia (OP). The patient received 9 months of anti-PD-1 pembrolizumab when he presented with dry cough and fatigue. The patient developed a solitary nodular lung lesion mimicking a newly occurred metastatic lesion in the lung without a significant circulating tumor marker increase. Sputum analysis was negative for acid-fast bacilli and fungi. A computed tomography-guided percutaneous lung biopsy was conducted and showed alveolar fibrous thickness and various lymphocyte infiltration. Immunotherapy-related OP was identified, and he subsequently responded well to corticosteroids. This case describes a clinical situation, where PD-1-induced OP is radiologically similar to NSCLC disease progression in the lungs. Oncologists should be aware of uncommon pulmonary PD-1/PD-L1 inhibitor toxicity. Lung biopsy may help to distinguish immune-related pneumonitis, lung infections, and progressive nodular lesions.

BACKGROUND: Immune checkpoint inhibitors have potential applications in treating various cancers but are associated with immune-related adverse events, such as inflammation, in a wide range of organs; however, allergic inflammation caused by these agents has not been extensively studied.
METHODS: A 65-year-old man was diagnosed with a kidney neuroendocrine carcinoma. Three months after kidney resection surgery, the tumor cells had metastasized to his liver and lymph nodes. Subsequently, the patient started chemotherapy; however, regardless of treatment, the tumor grew, and the patient experienced a series of adverse effects, such as taste disorder, anorexia, and general fatigue. Finally, he was administered a programmed cell death (PD)-1 inhibitor, nivolumab (biweekly, toal 200 mg/body), which was effective against kidney carcinoma. However, the patient had a bronchial asthma attack at 22 cycles of nivolumab treatment and chest computed tomography (CT) revealed an abnormal bilateral shadow after 37 cycles of nivolumab treatment. Bronchoscopy findings revealed eosinophil infiltration in the lungs along with severe alveolar hemorrhage. Paranasal sinus CT scanning indicated sinusitis and nerve conduction analysis indicated a decrease in his right ulnar nerve conduction velocity. Based on these findings, the patient was diagnosed with eosinophilic granulomatosis with polyangiitis; he was treated with prednisolone, which alleviated his bronchial asthma. To restart nivolumab treatment, the dose of prednisolone was gradually tapered, and the patient was administered a monthly dose of mepolizumab and biweekly dose of nivolumab. To date, there have been no bronchial attacks or CT scan abnormalities upon follow up.
CONCLUSIONS: We present a rare case in which a patient with cancer was diagnosed with eosinophilic granulomatosis with polyangiitis following treatment with a PD-1 inhibitor. Blockade of PD-1 and the programmed cell death ligand (PD-L) 1/PD-1 and PD-L2/PD-1 signaling cascade may cause allergic inflammation. Further studies are needed to identify the specific mechanisms underlying allergic inflammation after PD-1 blockade.

Immune checkpoint inhibitors, including antibodies targeting programmed cell death protein-1 (PD-1) and its receptor programmed cell death ligand-1 (PD-L1), represent promising therapeutic strategies for advanced human malignancies. However, a subgroup of patients experiences various autoimmune toxicities, termed immune-related adverse events (irAEs), that occur as a result of on-target and off-tumor autoimmune responses. Although irAEs are generally confirmed to be less severe than toxicities caused by conventional chemotherapy and targeted therapy, uncommon irAEs, such as immune thrombocytopenia, may occur with a very low incidence and sometimes be severe or fatal. This review focuses on the epidemiology, clinical presentation, and prognosis of immune thrombocytopenia occurring in advanced cancer patients induced by immune checkpoint inhibitors, especially in those with PD-1 or PD-L1 inhibitor treatment. We also first present one patient with non-small cell lung cancer who received the PD-L1 inhibitor durvalumab and developed severe thrombocytopenia.