What are the considerations for using immune checkpoint inhibitors, such as pembrolizumab (pembrolizumab) or nivolumab (nivolumab), in breast cancer patients with celiac disease?

Immune Checkpoint Inhibitors in Breast Cancer Patients with Celiac Disease

Immune checkpoint inhibitors should be used with caution in breast cancer patients with celiac disease due to the risk of exacerbating or unmasking celiac disease, but they are not absolutely contraindicated when clinically indicated.

Indications for Immune Checkpoint Inhibitors in Breast Cancer

According to current guidelines, immune checkpoint inhibitors have specific indications in breast cancer:

• For metastatic triple-negative breast cancer (TNBC) with PD-L1 expression, immune checkpoint inhibitors (atezolizumab plus nab-paclitaxel or pembrolizumab plus chemotherapy) are recommended as first-line therapy 1
• For early-stage TNBC (stage II-III), neoadjuvant chemotherapy plus pembrolizumab is recommended, followed by adjuvant pembrolizumab 1

Special Considerations for Celiac Disease Patients

Risk Assessment

Patients with celiac disease represent a special population when considering immune checkpoint inhibitors due to:

1. Potential for disease exacerbation: Multiple case reports document unmasking or worsening of celiac disease with immune checkpoint inhibitors 2, 3, 4, 5, 6

2. Autoimmune predisposition: Patients with pre-existing autoimmune conditions may be at higher risk for immune-related adverse events (irAEs) 1

Pre-treatment Evaluation

Before initiating immune checkpoint inhibitors in breast cancer patients with celiac disease:

• Ensure celiac disease is well-controlled on a gluten-free diet
• Obtain baseline celiac serologies (anti-tissue transglutaminase antibodies)
• Consider baseline endoscopy if celiac disease status is uncertain
• Document baseline gastrointestinal symptoms

Monitoring Protocol

For breast cancer patients with celiac disease receiving immune checkpoint inhibitors:

• More frequent monitoring of gastrointestinal symptoms than standard protocols
• Lower threshold for endoscopic evaluation with biopsies if new or worsening symptoms occur
• Regular monitoring of celiac serologies during treatment
• Early involvement of gastroenterology specialists in the care team

Management of Immune-Related Adverse Events

If celiac disease flares or other gastrointestinal irAEs develop:

1. For mild symptoms (grade 1): Continue immune checkpoint inhibitors with close monitoring and reinforcement of strict gluten-free diet 1

2. For moderate symptoms (grade 2): Consider temporary hold of immune checkpoint inhibitors, strict gluten-free diet, and symptom management; resume when symptoms improve to grade 1 1

3. For severe symptoms (grade 3-4): Hold immune checkpoint inhibitors, initiate corticosteroids (1-2 mg/kg/day of prednisone or equivalent), and consider permanent discontinuation based on severity and response 1

Treatment Algorithm

1. Assess baseline risk:

   • Well-controlled vs. poorly controlled celiac disease
   • History of other autoimmune conditions
   • Severity of breast cancer and need for immune checkpoint inhibitors

2. Select appropriate regimen:

   • For TNBC requiring immunotherapy, use standard recommended regimens
   • Consider single-agent over combination immunotherapy (nivolumab/ipilimumab) as combination therapy has higher irAE risk 1

3. Implement enhanced monitoring:

   • More frequent clinical assessments
   • Lower threshold for diagnostic evaluation
   • Proactive management of symptoms

Practical Considerations

• The decision to use immune checkpoint inhibitors should prioritize cancer outcomes (mortality and morbidity) while managing the risk of celiac disease exacerbation
• Case reports suggest that some patients can successfully continue immune checkpoint inhibitors with dietary management of celiac disease 4
• The risk of celiac disease exacerbation should not automatically preclude the use of potentially life-saving immunotherapy for aggressive breast cancers

Pitfalls and Caveats

• Misdiagnosis of immune checkpoint inhibitor-induced colitis when symptoms may actually represent celiac disease flare
• Failure to distinguish between different gastrointestinal irAEs (colitis vs. enteritis vs. celiac disease)
• Unnecessary permanent discontinuation of effective cancer therapy when symptoms might be manageable with dietary modifications and supportive care
• Delayed recognition of celiac disease exacerbation leading to malnutrition and treatment complications

In summary, while caution is warranted when using immune checkpoint inhibitors in breast cancer patients with celiac disease, these treatments can be administered with appropriate monitoring and management strategies when clinically indicated for breast cancer treatment.