Abstract
Background
Immune checkpoint inhibitor (ICPI)-mediated diarrhea and colitis is the leading cause of discontinuation of ICPI therapy in patients with malignancy. Existing literature on predictors of adverse outcomes is limited. We evaluated the association between risk factors, concomitant Clostridioides difficile infection (CDI), and abdominal CT scan findings of colitis on outcomes in patients with ICPI-related diarrhea and colitis.
Methods
A retrospective study was conducted for patients who received an ICPI for treatment of malignancy and developed diarrhea or colitis, with endoscopic findings consistent with ICPI colitis. Variables including smoking history, proton pump inhibitor (PPI) use, non-steroidal anti-inflammatory (NSAID) use, concomitant CDI, and abdominal CT scan findings were extracted. The Common Terminology Criteria for Adverse Events (CTCAE) criteria was used to determine diarrhea and colitis severity. We analyzed the effect on risk factors on outcomes including hospitalization rates, diarrhea and colitis severity, and mortality at 1 year. Statistical analysis comprised of descriptive statistics and univariate and multivariate logistic regression analyses.
Results
There were 33 patients with histologically proven ICPI-related colitis with median age 70 years (28–92). Seventeen patients (52%) had melanoma and 24 patients (73%) had metastatic disease (Table 1). There was no association between age, gender, smoking history, PPI use, NSAID use on rates of hospitalization, toxicity severity, or mortality related to ICPI-related diarrhea or colitis (p>0.05) on univariate analysis. CDI at diagnosis was associated with a higher grade of toxicity (p=0.04) and higher rate of mortality at 1-year follow-up (p=0.03) compared to patients with a negative GI pathogen panel; however, this effect was not seen on multivariate analysis controlling for age and cancer stage (p>0.05). In patients with metastatic malignancy, there were significant higher rates of hospitalization for ICPI-colitis compared to those without metastatic disease on multivariate analysis controlling for age (OR, 4.53 [95% CI, 1.11–35.99]). In patients with CT scan findings consistent with colitis, there was a significantly higher rate of hospitalization compared to patients without these imaging findings on multivariate analysis controlling for age and cancer stage (OR, 2.99 [95% CI, 1.22–6.64]).
Conclusions
Patients with metastatic malignancy or CT scan findings consistent with colitis had a significantly higher rate of hospitalization for ICPI colitis compared to patients with non-metastatic disease or without radiographic features of colitis. CDI at diagnosis was associated with mortality and higher grade of toxicity. Further investigation is needed to examine predictors of adverse outcomes with use of ICPI to reduce morbidity and mortality in this patient population.