Clostridioides difficile infection in cancer patients receiving immune checkpoint inhibitors

Vasavada, Shaleen; Panneerselvam, Kavea; Amin, Rajan; Varatharajalu, Krishnavathana; Okhuysen, Pablo C.; Wang, Jianbo; Grivas, Petros; Thomas, Anusha Shirwaikar; Wang, Yinghong

doi:10.20524/aog.2022.0722

Cited by 9 publications

(9 citation statements)

References 28 publications

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“…A retrospective single-center study explored the attributes of CDI in patients undergoing therapy with ICI in the presence of IMDC. The study concluded that the concurrence of CDI and IMDC is associated with prolonged symptom duration (20 vs. 5 days, p=0.003) and a reported higher rate of grade 3-4 diarrhea (41% vs. 7%, p=0.033) [ 13 ]. Similarly, in our case, the patient was started on treatment for the suggested IMDC with high-dose steroids.…”

Section: Discussionmentioning

confidence: 99%

Checkpoint Inhibitor Colitis With Superimposed Clostridioides difficile Infection

Mohammad¹,

Kusnik²,

Mostafa³

et al. 2023

Cureus

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Immune checkpoint inhibitors (ICI) are commonly used for various malignancies. A particular checkpoint inhibitor is the anti-PD-1 antibody pembrolizumab. Immune-mediated diarrhea and colitis (IMDC) is the most frequently observed immune-related adverse event (irAE) involving the gastrointestinal system. Although immune-mediated colitis precipitated by pembrolizumab is rarely life-threatening, it often necessitates a detailed diagnostic workup, including stool studies, imaging, and colonoscopy, to establish an accurate diagnosis. The coexistence of IMDC and Clostridioides difficile infection is not well understood, but patients undergoing pembrolizumab treatment have comparable risk factors to those who develop C. difficile infection. We report a case of a 76-year-old female with nonmetastatic non-small cell lung cancer who was diagnosed with IMDC responsive to steroid treatment but later developed worsening diarrhea leading to a diagnosis of checkpoint inhibitor colitis with superimposed C. difficile infection.

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Section: Discussionmentioning

confidence: 99%

Checkpoint Inhibitor Colitis With Superimposed Clostridioides difficile Infection

Mohammad¹,

Kusnik²,

Mostafa³

et al. 2023

Cureus

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“…This hypothesis has been proposed and evaluated in several investigations. Previous evidence suggests that ICI-related colitis increases susceptibility to gastrointestinal tract infections such as Clostridioides difficile 37 , non- C. diff. bacterial, and viral infections 38 .…”

Section: Discussionmentioning

confidence: 99%

The Safety of Immunosuppressants Used in the Treatment of Immune-Related Adverse Events due to Immune Checkpoint Inhibitors: a Systematic Review

Machado,

Ratliff,

Abdelwahab

et al. 2023

J. Cancer

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Purpose: Immune checkpoint inhibitor (ICI) use can lead to immune-related adverse events (irAEs) that require treatment with immunosuppressive medications in moderate to severe cases. Oncology society guidelines recommend systemic steroids and immunosuppressants such as infliximab and vedolizumab for the treatment of refractory cases. Limited information is available about the safety profile and potential adverse effects of these immunosuppressants. We have investigated the safety profile of multiple immunosuppressants which are used in the treatment of ICI-related irAEs. Methods: We performed a systematic review of studies reporting irAEs, from ICI use, and their medical management with immunosuppressants in adult cancer patients. We searched MEDLINE, EMBASE, Cochrane Library, and ClinicalTrials.gov from inception through September 1, 2022, using the following keywords or their equivalents: ICI, immunosuppressant, and irAE. We extracted observational studies and clinical trials that matched our criteria. A random effects model was used to estimate the overall incidence of infections associated with the treatment of irAEs. Results: Among the 11 studies included in this review (1036 total patients), melanoma (548 patients, 52.9%) was the most common primary cancer, followed by lung cancer (139 patients, 13.4%) and genitourinary cancers (131 patients, 12.6%). PD-1/PD-L1 monotherapy (460 patients, 44.4%) was used most, followed by a combination of PD-1/PD-L1 and CTLA-4 therapy (350 patients, 33.8%) and CTLA-4 monotherapy (226 patients, 22%). A total of 1024 (98.8%) patients had their irAEs treated with systemic steroids with majority having colitis and hepatobiliary irAEs; 335 patients (32.3%) were also treated with infliximab (mainly for colitis). Our review found 22.3% of patients treated for irAEs developed infectious adverse events (95% CI: 15.6%-29.1%, p<0.001). Among the 3 studies reporting the types of infections (41 total patients), bacterial (80.5%), followed by fungal (36.6%), infections were most common. Conclusions: Adverse events from irAE treatment occurred in about one-third of patients that received either steroids or a combination of steroids and other immunosuppressants. Clinicians should be aware of these immunosuppressant-related adverse effects, which can negatively impact cancer treatment and patient outcomes, when treating irAEs and consider shortening treatment duration or using alternative strategies when possible to mitigate these complications, future prospective studies should further investigate the safety of immunosuppressants in treating irAEs.

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“…In a retrospective study, 27 among 345 patients who received 492 terms of chemotherapy regimens, 36 (7.3%) had grade 2 or higher diarrhea, and eight had CDI without prior exposure to antibiotics. In a prospective study, 27 five cases of CDI were diagnosed among 263 patients with lung In a recent retrospective study, 28 among 421 patients with cancer receiving immunotherapy including programmed death-1 or its ligand inhibitors or cytotoxic T-lymphocyte-associated antigen 4 inhibitors, 41 patients had CDI (9.7%). Prior use of antibiotics and PPIs were significantly more common among individuals who CDI after immune checkpoint inhibitors exposure.…”

Section: Discussionmentioning

confidence: 99%

“…In a recent retrospective study, 28 among 421 patients with cancer receiving immunotherapy including programmed death-1 or its ligand inhibitors or cytotoxic T-lymphocyte-associated antigen 4 inhibitors, 41 patients had CDI (9.7%). Prior use of antibiotics and PPIs were significantly more common among individuals who developed CDI after immune checkpoint inhibitors exposure.…”

Section: Discussionmentioning

confidence: 99%

Clinical Impact of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Associated Clostridioides difficile Infection Among Patients with Lung Cancer

Chung

Lin

Hung

et al. 2022

OTT

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Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKIs)-associated Clostridioides difficile infection (CDI) among lung cancer patients have been reported in case reports and adverse events reporting system databases in the United States and Japan, but clinical data remained insufficient. This study aims to evaluate CDI in lung cancer patients receiving EGFR-TKIs. Methods: We conducted a retrospective cohort study using multi-institutional electronic medical records database. We included patients aged older than 20 years diagnosed with lung cancer and treated with EGFR-TKIs (gefitinib, erlotinib, afatinib). We defined EGFR-TKI initiation date as the index date and occurrence of diarrhea with CDI or without CDI as the event date. We followed patients from the index date until the event date, ICU admission, death, or 12/31/2019. Results: We included 2242 diarrhea patients, 51 were EGFR-TKI with CDI cohort, and 2191 were diarrhea without CDI cohort. Patients who were concurrently taking antibiotics (hazard ratio [HR], 3.30; 95% CI, 1.67-6.5) and systemic steroids (HR, 4.9; 95% CI, 2.65-9.06) had an increased risk of CDI. First-generation EGFR-TKIs tended to be associated with an increased risk of CDI compared with afatinib (HR, 1.81, 95% CI, 0.94-3.47). EGFR-TKI with CDI had a higher ICU admission rate (HR, 3.42, 95% CI, and mortality rate (HR, 2.34, 95% CI,) than diarrhea without CDI. Conclusion: Patients with CDI had higher ICU admission rates and mortality rates than those without CDI. Concurrent use of antibiotics and systemic steroids were risk factors for CDI among patients with lung cancer receiving EGFR-TKIs. Afatinib was not associated with a higher risk of CDI than first-generation EGFR-TKIs.

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Clostridioides difficile infection in cancer patients receiving immune checkpoint inhibitors

Cited by 9 publications

References 28 publications

Checkpoint Inhibitor Colitis With Superimposed Clostridioides difficile Infection

Checkpoint Inhibitor Colitis With Superimposed Clostridioides difficile Infection

The Safety of Immunosuppressants Used in the Treatment of Immune-Related Adverse Events due to Immune Checkpoint Inhibitors: a Systematic Review

Clinical Impact of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Associated Clostridioides difficile Infection Among Patients with Lung Cancer

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