Can Jemperli (dostarlimab) cause immune-mediated colitis?

Can Jemperli Cause Colitis?

Yes, Jemperli (dostarlimab) can cause immune-mediated colitis, occurring in 1.3% of patients, with both Grade 2 and Grade 3 severity documented in clinical trials. 1

Incidence and Severity

According to the FDA label, immune-mediated colitis occurred in 8 out of 605 patients (1.3%) receiving Jemperli as monotherapy, with equal distribution between Grade 2 (0.7%) and Grade 3 (0.7%) cases 1. While this incidence is lower than with CTLA-4 inhibitors like ipilimumab, it remains a clinically significant adverse event requiring vigilant monitoring.

Colitis led to permanent discontinuation in 0.2% of patients, and systemic corticosteroids were required in 75% of affected patients 1. Of the 4 patients who had Jemperli temporarily withheld and then reinitiated, 1 experienced recurrence of colitis, highlighting the risk of rechallenge.

Clinical Presentation and Monitoring

Patients should be counseled to immediately report:

• Abdominal pain, cramping, or distention
• Blood or mucus in stool
• Changes in bowel habits (increased frequency or consistency)
• Fever or signs of dehydration

The FDA label emphasizes that cytomegalovirus infection/reactivation can occur in patients with corticosteroid-refractory immune-mediated colitis, necessitating repeat infectious workup in refractory cases 1.

Management Algorithm

Grade 1 (< 4 stools/day increase):

• Continue Jemperli with close monitoring 2
• Supportive care (loperamide only after ruling out infection)
• Monitor every 3 days until stabilized
• Consider gastroenterology consultation if prolonged

Grade 2 (4-6 stools/day increase):

• Hold Jemperli immediately 2
• Obtain stool studies (culture, C. diff, CMV, parasites) and blood work (CBC, CMP, TSH) 2
• Perform colonoscopy with biopsy - this is critical as colonic ulceration predicts steroid-refractory disease requiring early biologic therapy 3, 2
• Start prednisone 1 mg/kg/day until improvement to Grade 1, then taper over 4-6 weeks 2
• Consider early infliximab or vedolizumab if high-risk endoscopic features (ulceration) or no improvement within 72 hours 3, 2

Grade 3 (≥7 stools/day, hospitalization indicated):

• Hospitalize patient 2
• Prednisone 1-2 mg/kg/day (IV methylprednisolone if concurrent upper GI inflammation suspected) 2
• Consider early biologics (infliximab 5 mg/kg or vedolizumab 300 mg IV) if inadequate response after 3 days 3, 2
• Repeat colonoscopy if immunosuppression-refractory 2
• Consider permanently discontinuing Jemperli 2

Grade 4 (life-threatening):

• Permanently discontinue Jemperli 2
• Inpatient care mandatory
• IV methylprednisolone 1-2 mg/kg/day 2
• Early biologics if no response after 3 days 2

Critical Management Considerations

Approximately one-third of patients with immune checkpoint inhibitor colitis fail first-line glucocorticoid treatment 3. The only predictive factor for requiring second-line immunosuppression is colonic ulceration on endoscopy - not CTCAE grading 3. This makes early endoscopic evaluation essential for Grade ≥2 cases.

For biologic selection between infliximab and vedolizumab:

• Avoid infliximab in hematologic malignancies (lymphoma risk) and severe heart failure 3
• Avoid infliximab if concurrent immune-mediated hepatitis (can induce hepatitis) 3, 2
• Consider vedolizumab as first-line if these contraindications exist
• Response to biologics typically occurs within 1 week (faster than in IBD) 3

Rechallenge Considerations

Resuming Jemperli after colitis resolution carries risk but may be considered when:

• Symptoms improve to Grade ≤1
• Steroid taper completed
• Endoscopic and histologic remission achieved, or fecal calprotectin ≤116 mg/g 2
• Risk-benefit analysis favors continued cancer treatment

The FDA data shows 1 of 4 patients (25%) who reinitiated Jemperli experienced colitis recurrence 1, making careful patient selection and monitoring essential.

Common Pitfalls

• Delaying endoscopy in Grade ≥2 cases - missing ulceration delays appropriate escalation to biologics
• Inadequate infectious workup - CMV reactivation can complicate steroid-refractory cases 1
• Premature steroid taper - maintain at least 4-6 week taper to prevent relapse 3, 2
• Using topical budesonide for Grade 1 - lacks evidence and may interfere with antitumor response 2