Superimposed Clostridium difficile Infection During Checkpoint Inhibitor Immunotherapy-induced Colitis

Babacan, Nalan; Tanvetyanon, Tawee

doi:10.1097/cji.0000000000000270

Cited by 17 publications

(15 citation statements)

References 15 publications

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“…In this cohort, the proportion of significant AEs seemed to be higher compared with prior safety data reported in the clinical studies with single-agent ICIs, which may be explained by the differences of the patient population included. ICI-related attribution was not reported for the AEs observed in our study, but patients on immune therapies who often develop autoimmune dermatitis and colitis with superimposed C. difficile infection have also been observed in such cases (19).…”

Section: Discussionmentioning

confidence: 50%

Outcomes With First-Line PD-1/PD-L1 Inhibitor Monotherapy for Metastatic Renal Cell Carcinoma (mRCC): A Multi-Institutional Cohort

et al. 2020

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Introduction: The treatment landscape of metastatic renal cell carcinoma has advanced significantly with the approval of combination regimens containing an immune checkpoint inhibitor (ICI) for patients with treatment-naïve disease. Little information is available regarding the activity of single-agent ICIs for patients with previously untreated mRCC not enrolled in clinical trials. Methods: This retrospective, multicenter cohort included consecutive treatment-naïve mRCC patients from six institutions in the United States who received ≥1 dose of an ICI outside a clinical trial, between June 2017 and October 2019. Descriptive statistics were used to analyze outcomes including objective best response rate (ORR), progression-free survival (PFS), and tolerability. Results: The final analysis included 27 patients, 70% men, median age 64 years (range 42-92), 67% Caucasian, and 33% with ECOG 2 or 3 at baseline. Most patients had intermediate risk (85%, IMDC) with clear cell (56%), papillary (26%), unclassified (11%), chromophobe (4%), and translocation (4%) RCC. All patients had evidence of metastatic disease involving the lungs (59%), lymph node (41%), CNS (19%), liver (11%), adrenal gland (11%), and bone (11%). The median time on ICI was 3.1 (0.1-26.8) months, and the median PFS was 6.3 (95% CI, 0-18.6) months. Among the 21 patients with an evaluable response, the best ORR was 33%, including two complete responses and five partial responses. The ORR was 29% (n = 1 complete response, n = 5 partial response) in clear cell and 5% (n = 1 complete response) in non-clear cell RCC. Adverse events (AEs) of any cause were reported in 37% and included fatigue (11%), dermatitis (11%), diarrhea (7%), and shortness of breath (7%). Significant AEs (30%) included shortness of breath (7%), acute kidney injury (4%), dermatitis (4%), Clostridium difficile infection (4%), cerebrovascular accident (4%), and fatigue (7%). Three patients discontinued therapy due to grade 4 AEs. Barata et al. PD-1/PD-L1 Inhibitor Monotherapy in RCC Conclusions: In this multi-institutional case series, single-agent ICI demonstrated objective responses and was well tolerated in a heterogeneous treatment-naïve mRCC cohort. ICI monotherapy is not the standard of care for patients with mRCC, and further investigation is necessary to explore predictive biomarkers for optimal treatment selection in this setting.

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Section: Discussionmentioning

confidence: 50%

Outcomes With First-Line PD-1/PD-L1 Inhibitor Monotherapy for Metastatic Renal Cell Carcinoma (mRCC): A Multi-Institutional Cohort

et al. 2020

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“…Nearly 20%-30% of patients would experience recurrent grade 3 CIC (195,233). In our analysis, 12.5% (4/32) of patients (36,43,50,54) were retreated with the same ICI therapy used before, one of which experienced the recurrence of grade 3 enterocolitis (54). All of these patients who were reintroduced to ICI therapy harbored deteriorated/recurrent CIC outcomes (P = 0.037) (Table 4).…”

Section: Rechallenge and Recurrencementioning

confidence: 80%

“…They found that most of the patients need steroid, while a minority of them required IFX or vedolizumab, regardless of whether in the initial or recurrent episode. Our analysis showed that 25% (8/32) of patients (36,41,43,46,48,54,57) had recurrent ICI-mediated colitis without ICI retreatment, which received subsequent therapy involving probiotics, antidiarrheal drugs, antiviral drugs, steroid, and immunosuppressants. Four cases with CIC finally did not improve or deteriorate after the second treatment (36,41,48,54).…”

Section: Rechallenge and Recurrencementioning

confidence: 87%

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Immune Checkpoint Inhibitor-Associated Colitis: From Mechanism to Management

et al. 2021

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Immune checkpoint inhibitors (ICIs), as one of the innovative types of immunotherapies, including programmed cell death-1 (PD-1), programmed cell death-ligand 1 (PD-L1), and cytotoxic T lymphocyte antigen 4 (CTLA-4) inhibitors, have obtained unprecedented benefit in multiple malignancies. However, the immune response activation in the body organs could arise immune-related adverse events (irAEs). Checkpoint inhibitor colitis (CIC) is the most widely reported irAEs. However, some obscure problems, such as the mechanism concerning gut microbiota, the confusing differential diagnosis with inflammatory bowel disease (IBD), the optimal steroid schedule, the reintroduction of ICIs, and the controversial prognosis features, influence the deep understanding and precise diagnosis and management of CIC. Herein, we based on these problems and comprehensively summarized the relevant studies of CIC in patients with NSCLC, further discussing the future research direction of this specific pattern of irAEs.

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“…For instance, 5-Fluorouracil (5-FU) which is commonly used to treat solid cancers has been found to alter the intestinal microbiota [ 30 , 31 ,]. Recently, there have been frequent reports on the association of newer molecular therapies with Clostridioides difficile infection [ 32 ]. In our patient data, we could not retrieve detailed information regarding the chemotherapy/immunotherapy protocols used due to the inaccessibility to patient oncological treatment charts.…”

Section: Discussionmentioning

confidence: 99%

To study the contributing factors and outcomes of Clostridioides difficile infection in patients with solid tumors

Sahu

Mishra

Jindal

et al. 2021

Heliyon

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Background Clostridioides difficile infection (CDI) is a considerable healthcare burden, and now identified as the leading cause of acquired diarrheal illness in patients receiving antibiotics. Patients with malignancies are more prone to acquire CDI, owing to their frequent exposure to risk factors. Objective This study aims to investigate the factors affecting the outcome of Clostridioides Difficile Infection in patients with solid tumors at our community healthcare center. Methods This is a retrospective study that included a total of 59 patients with solid tumors who were hospitalized for Clostridioides difficile infection. Results The median age of the study population was 79 years with 39 males and 20 females. The patients had a diagnosis of a malignancy involving the following sites: prostate (25), lung (19), colon (7), bladder (4), breast (3), and renal (1). There were 52 cases of first time and 7 cases of recurrent CDI admissions. 40 patients were detected to have CDI at presentation while 19 patients were diagnosed with CDI after admission. CDI was categorized as follows: non-severe (29), severe (28), and very severe (2). There were 33 patients on chemotherapy and 20 patients undergoing radiotherapy. Twenty-seven patients had a recent history of cancer care-related procedures or interventions. Twenty-nine patients were from either a rehabilitation center or a long-term nursing care facility. There were 39 recent hospitalizations with 29 patients receiving antibiotics. Almost half of the patients were on proton pump inhibitors (29) and 12 were on steroids (20.3%) at the time of developing CDI. Patients with a high-risk qSOFA score of 2 or more (p-value = 0.008) or a high white blood cell count of >15 × 10 9 /L (p-value = 0.016) at the time of admission were found to have higher in-hospital mortality. Critical care data suggested that 9 patients required intensive care, 7 patients required vasopressor support, and 6 needed mechanical ventilation. Patients were treated with either vancomycin alone (13), or metronidazole alone (25), or combination therapy with vancomycin + metronidazole (21). The median duration of hospital stay was 6 days with 11 fatalities (18.64%). Conclusions CDI causes significant morbidity in patients with malignancies. A high qSOFA score and leukocytosis are significantly associated with high morbidity and thus should be used to prioritize and intensify inpatient care of these patients.

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Superimposed Clostridium difficile Infection During Checkpoint Inhibitor Immunotherapy-induced Colitis

Cited by 17 publications

References 15 publications

Outcomes With First-Line PD-1/PD-L1 Inhibitor Monotherapy for Metastatic Renal Cell Carcinoma (mRCC): A Multi-Institutional Cohort

Outcomes With First-Line PD-1/PD-L1 Inhibitor Monotherapy for Metastatic Renal Cell Carcinoma (mRCC): A Multi-Institutional Cohort

Immune Checkpoint Inhibitor-Associated Colitis: From Mechanism to Management

To study the contributing factors and outcomes of Clostridioides difficile infection in patients with solid tumors

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