- Researchers at Massachusetts General Hospital have defined a subset of enterocolitis related to checkpoint inhibitor (CPI) therapy that they term "CPI microscopic colitis"
- In a retrospective study of 38 patients confirmed to have CPI enterocolitis, 13 (34%) met the team's definition of CPI microscopic colitis
- Twelve of those 13 patients (92%) were treated with budesonide
- Only 23% of patients with CPI microscopic colitis had to discontinue CPI therapy because of toxicity, compared with 84% of patients with non-microscopic colitis (P < .001)
- Among patients who remained on immunotherapy, patients with microscopic colitis were able to receive a significantly greater number of additional infusions than patients with non-microscopic colitis (5.8 vs. 1.6, P = .03)
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Colitis and enterocolitis are among the most common and severe immune-related adverse events associated with checkpoint inhibitor (CPI) immunotherapy for cancer. CPI enterocolitis usually responds to systemic corticosteroids, but those drugs have substantial side effects of their own and can limit antitumor immunity.
Most patients with CPI enterocolitis have mucosal changes, but some have normal-appearing mucosa on endoscopy. That's also true of patients with microscopic colitis, which can often be successfully treated with budesonide, a corticosteroid that's formulated to target the colon and has limited systemic effects.
Michael Dougan, MD, PhD, director of the Mass General GI Center for Cancer Complications and gastroenterologist in the Division of Gastroenterology, and colleagues have defined a subset of CPI enterocolitis that they term "CPI microscopic colitis." In the Journal for ImmunoTherapy of Cancer, they explain that it can be identified endoscopically and responds to budesonide in many cases.
The research team reviewed data on 55 adults who underwent flexible sigmoidoscopy for evaluation of suspected CPI enterocolitis at Mass General between March 1, 2017, and March 1, 2019. Twenty-one of the patients had melanoma, seven had non-small-cell lung cancer and 10 had other solid or hematological malignancies.
Thirty-eight patients were confirmed to have CPI enterocolitis, and 13 of them (34%) met the team's definition of CPI microscopic colitis, which is:
- Clinical evidence of colitis
- No endoscopic inflammation (Mayo Endoscopic Score [MES] of 0)
- Lymphocytic- or collagenous-pattern colitis on histopathologic evaluation of a biopsy specimen
- No evidence of involvement of the upper gastrointestinal tract (difficult to treat with current budesonide formulations)
Of the other 25 patients, 19 had enterocolitis with an MES ≥1, five had no endoscopic evidence of mucosal inflammation but had pathologic evidence of enteritis and for one, the MES could not be determined. Together those patients comprised the non-microscopic colitis cohort.
Twelve patients with microscopic colitis (92%) were treated with budesonide, and three with non-microscopic colitis (12%) were treated with budesonide in addition to other corticosteroids. Systemic corticosteroids were used by 23% and 88% of the groups, respectively (P < .001).
There were three co-primary outcome measures:
- Median time from symptom onset to resolution: 50 days in both groups
- Absence of symptoms three months after initial resolution: 82% in the microscopic colitis vs. 90% in the group with non-microscopic colitis (P = NS)
- Discontinuation of CPI due to toxicity: 23% vs. 84% (P < .001)
Among patients who remained on immunotherapy, patients with microscopic colitis were able to receive a significantly greater number of additional infusions than patients with non-microscopic colitis (5.8 vs. 1.6, P = .03).
The Case for Routine Endoscopy
For patients suspected of having CPI enterocolitis, current treatment guidelines recommend considering endoscopic evaluation only if symptoms are severe. However, in this study, a third of patients with suspected CPI enterocolitis proved to have CPI microscopic colitis and responded to a drug that reduces or eliminates the need for systemic corticosteroids.
Thus, there is a compelling rationale for routinely using endoscopy to stratify cancer patients on CPI therapy who are suspected of having developed gastrointestinal inflammation.
Further research is required to determine whether CPI microscopic colitis is a distinct pathologic entity or a milder subtype of CPI enterocolitis that has a distinct treatment response.
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