If a patient develops lichen planus while receiving Keytruda (pembrolizumab), should the drug be stopped and how should it be managed?

Management of Keytruda-Induced Lichen Planus

For mild lichen planus from Keytruda, continue the drug and treat with high-potency topical steroids; for moderate or severe cases, hold Keytruda until symptoms improve to grade 1, then consider rechallenge if body surface area involvement is <30%. 1

Severity-Based Treatment Algorithm

Mild (Grade 1) Lichen Planus

• Continue Keytruda at current dose
• Start high-potency topical steroids (clobetasol 0.05% or fluocinonide 0.05% cream/ointment) twice daily 1
  • Use gel formulation for oral/mucosal lesions
  • Use solution for scalp involvement
  • Use cream/lotion/ointment for trunk and extremities
• Add tacrolimus 0.1% ointment as alternative or adjunct 1
• Consider oral antihistamines for pruritus 1

Moderate (Grade 2) Lichen Planus

• Hold Keytruda until symptoms controlled 1
• Continue high-potency topical steroids twice daily
• Add oral prednisone (taper over 3 weeks once improved to grade 1) 1
• Consider narrow-band UVB phototherapy if available 1
• Rechallenge criteria: Resume Keytruda when symptoms controlled AND body surface area involvement <30% 1

Severe (Grade 3-4) Lichen Planus

• Hold Keytruda immediately 1
• Start prednisone or IV methylprednisolone 1
• Refer to dermatology 1
• Consider steroid-sparing agents if prolonged treatment needed:
  • Acitretin (if no childbearing potential) 1, 2, 3
  • Doxycycline plus nicotinamide 1
  • Other immunosuppressants: azathioprine, cyclosporine, hydroxychloroquine, methotrexate, or mycophenolate mofetil 1

Key Clinical Pearls

Timing: Lichen planus typically develops 6-12 weeks after starting Keytruda, affecting up to 6% of patients 1. However, it can occur even after discontinuation of therapy 4.

Presentation: Look for violaceous papules and plaques without scale on trunk/extremities with significant pruritus. Check for oral/vulvar erosions with white striae (Wickham's striae) 1.

Critical Pitfall: Hypertrophic lichen planus can mimic squamous cell carcinoma or keratoacanthoma clinically and histologically 3, 4. If lesions appear nodular or suspicious, obtain biopsy but consider empiric trial of high-potency topical steroids while awaiting pathology 3.

When to Permanently Discontinue Keytruda

Based on the FDA label 5, permanently discontinue Keytruda for:

• Grade 4 dermatologic toxicity
• Recurrent severe (Grade 3) reactions requiring systemic immunosuppression
• Inability to taper corticosteroids to ≤10 mg prednisone daily within 12 weeks

Real-World Evidence

Multiple case reports demonstrate successful continuation of Keytruda with conservative management 6, 2, 7. One patient with refractory oral lichen planus required Keytruda discontinuation but maintained stable cancer for 6 months off treatment 8. Another achieved complete resolution with topical clobetasol and oral acitretin while continuing pembrolizumab 3.

The evidence strongly supports attempting to continue Keytruda for mild disease and rechallenging for moderate disease once controlled, given the significant oncologic benefit and the generally manageable nature of this toxicity with appropriate dermatologic intervention.