Characteristics and Outcomes of Cancer Patients With Venous Thromboembolic Events After Treatment With Immune Checkpoint Inhibitors.

OBJECTIVE: This study aimed to describe the clinical characteristics and outcomes of patients with venous thromboembolism (VTE) after Immune checkpoint inhibitors (ICI), focusing on patients with gastrointestinal (GI) immune-related adverse events (irAE). METHODS: In this retrospective, single-center study, we report the clinical outcomes of adult cancer patients who developed a VTE within 2 years of ICI initiation. Patients were excluded if alternate causes of VTE were present apart from malignancy and cancer therapy. The cohort was classified into those with GI-irAE, non-GI-irAE, and no irAE. A control group with ICI exposure without irAE and VTE was selected for comparative analysis. RESULTS: Of all ICI-treated patients, 1891 (17.2%) were diagnosed with VTE. In all, 501 (4.6%) had no etiology for VTE aside from malignancy and cancer therapy. Of these, 137 patients were included and classified as: 44 GI-irAE, 42 non-GI-irAE, and 51 no irAE. Chemotherapy within 6 months of ICI therapy was associated with increased VTE risk. There was no difference in the clinical course between those exposed to chemotherapy versus ICI therapy alone, time from ICI initiation to VTE, and VTE type, recurrence, or related hospitalization. While there was no difference in VTE-related mortality, the GI-irAE group was associated with lower all-cause mortality and superior overall survival. CONCLUSION: Combined ICI and chemotherapy use increased VTE risk. There is a similar disease course of VTE after ICI exposure, regardless of other irAEs. Co-existing GI-irAE with VTE is associated with superior overall survival. Prospective studies are needed to evaluate the relationship between ICI therapy and VTE and irAE impact on VTE outcomes.

Immune checkpoint inhibitor-related gastrointestinal toxicity in patients with malignancy involving the luminal gastrointestinal tract and its impact on cancer outcomes.

Background: Immune checkpoint inhibitors (ICI) are known to cause immune-related adverse events (irAE) with the gastrointestinal (GI) tract among the most affected. Our knowledge of GI irAE in patients with luminal GI malignancies is poor. We aimed to characterize the incidence, clinical features, treatment, and outcomes of these GI irAEs. Methods: This was a retrospective study of patients with malignancies involving the luminal GI tract and GI irAEs at MD Anderson Cancer Center from January 2010 to June 2020. Clinical data were collected and analyzed. Results: Eighteen patients with luminal GI tract malignancies treated with ICIs had evidence of GI irAEs based on clinical symptoms and/or histology. The predominant GI irAE symptom was diarrhea (78%). Ten had non-ulcerative inflammation (56%) and 5 had ulcerative inflammation (28%) on endoscopy. Histologically, 3 patients (17%) had evidence of acute inflammation, 4 (22%) had chronic inflammation, and 9 (50%) had both. Ten patients (56%) received immunosuppressant treatment, which included steroids alone (n=2, 20%), steroids with biologics (infliximab or vedolizumab) (n=7, 70%), or biologics alone (n=1, 10%), with clinical remission in all cases. Of the 6 patients who previously had stable or ICI-responsive cancer and received immunosuppressants, none developed progression of GI luminal malignancy during the study period. Conclusions: GI irAEs occurred in 2.4% of patients treated with ICI for cancer involving the luminal GI tract. Immunosuppressant therapies (e.g., vedolizumab) appear to be effective for GI irAEs, showing no association with further GI luminal cancer progression, recurrence, or a subsequent poor response to ICI therapy.

Clinical Characteristics and Outcomes of Oral Mucositis Associated With Immune Checkpoint Inhibitors in Patients With Cancer.

BACKGROUND: Immune checkpoint inhibitor (ICI) therapy predisposes patients to immune-related adverse events (irAEs). Data are limited regarding the incidence, management, and outcomes of one such irAE: mucositis. In this study, we evaluated the clinical characteristics, disease course, treatment, and outcomes of ICI-mediated mucositis. METHODS: This was a retrospective, single-center study of patients who received ICI therapy and developed oral mucositis at The University of Texas MD Anderson Cancer Center from January 2009 to September 2019. Inclusion criteria included age ≥18 years, a diagnosis of oral mucositis and/or stomatitis based on ICD-9 and ICD-10 codes, and therapy using CTLA-4 or PD-1/L1 inhibitors alone or combined with other agents. RESULTS: We identified 152 patients with a mean age of 60 years, 51% of whom were men. Of the sample patients, 73% had stage IV cancer, with melanoma the most common (28%). Median time from ICI initiation to mucositis was 91 days. The most common clinical presentation of mucositis was odynophagia and/or oral pain (89%), 91% developed CTCAE grade 1-2 mucositis, and 78% received anti-PD-1/L1 monotherapy. Compared with anti-PD-1/L1-based therapy, anti-CTLA-4-based therapy was more frequently associated with earlier onset of mucositis (73 vs 96 days; P=.077) and a lower rate of symptom resolution (76% vs 92%; P=.029); 24% of patients required immunosuppressive therapy, which was associated with longer symptom duration (84 vs 34 days; P=.002) and higher mucositis recurrence rate (61% vs 32%; P=.006). ICI interruption was associated with worse survival (P=.037). Mucositis recurrence, immunosuppressant use, and presence of other irAEs did not affect survival. CONCLUSIONS: For ICI-mediated mucositis, a diagnosis of exclusion has not been well recognized and is understudied. Although the clinical symptoms of mucositis are mostly mild, approximately 25% of patients require immunosuppression. Mucositis recurrence can occur in approximately 39% patients. Our results showed that ICI interruption compromises overall survival.

Lymphocytic Esophagitis Is Not Similar to Eosinophilic Esophagitis Except for Seasonal Variation.

OBJECTIVE: Unlike eosinophilic esophagitis (EoE), there is no consensus on the minimum number of intraepithelial lymphocytes (IEL) that is diagnostic of lymphocytic esophagitis (LyE). The aim of this study was to determine whether significant correlations exist between the numbers of intraepithelial lymphocytes (IEL) in esophageal biopsies and clinical and endoscopic manifestations usually associated with EoE. METHODS: H&E slides from esophageal biopsies from 330 patients were reviewed. The number of IEL and intraepithelial eosinophils (IEE) per mm2 was counted in the area with the highest concentration in each biopsy. The numbers were then correlated with clinical and endoscopic findings. RESULTS: As expected, a higher number of IEE was significantly associated with food impaction (p=0.001), dysphagia (p=0.021), esophageal stricture (p=0.017), rings (P<0.0001), and furrows (p<0.0001). By contrast, there was no significant association between increased IEL and any of the aforementioned clinical and endoscopic features in the original 330 patients or in a subset of 233 patients with no IEE. Interestingly, the number of both IEE and IEL varied significantly by the season when the biopsy was obtained, being lowest in the fall and highest in the spring (p=0002 for IEE and p<0.0001 for IEL). CONCLUSION: In esophageal biopsies, increased IEL has no significant correlation with food impaction or dysphagia or with esophageal stricture, rings, or furrows. There is significant variation in the number of IEL depending on the season when the biopsy is obtained, which has not been previously reported.