What is the best course of action for a patient with a history of psoriasis who experiences a flare after being administered nivolumab (Opdivo) for cancer treatment?

Management of Nivolumab-Induced Psoriasis Flare

Continue nivolumab therapy while treating the psoriasis flare with topical corticosteroids, as the cancer mortality benefit outweighs the dermatologic toxicity, and most flares can be managed without discontinuing immunotherapy. 1, 2, 3

Immediate Assessment and Grading

Grade the severity of the psoriasis flare based on body surface area (BSA) involvement and functional impact:

• Grade 1 (BSA <10%): Continue nivolumab without interruption 1
• Grade 2 (BSA 10-30% or >30% with mild symptoms): Consider holding nivolumab temporarily and monitor weekly 1
• Grade 3 (BSA >30% with moderate-severe symptoms limiting self-care): Hold nivolumab and obtain urgent dermatology consultation 1
• Grade 4 (life-threatening, requiring hospitalization): Immediately discontinue nivolumab permanently 1

Rule out other causes of rash including infection, drug reactions, or severe cutaneous adverse reactions (SCAR) such as Stevens-Johnson Syndrome, toxic epidermal necrolysis, or DRESS syndrome, which mandate immediate nivolumab discontinuation. 1, 2

Treatment Algorithm by Severity

Grade 1 Flares (Most Common Scenario)

Continue nivolumab without interruption and initiate topical therapy: 1, 2, 3

• Apply high-potency topical corticosteroids (clobetasol propionate 0.05% or betamethasone dipropionate 0.05%) twice daily to affected plaques 4, 5
• Use topical emollients liberally 1, 2
• Add oral antihistamines for pruritus control 1
• In multicenter data of 76 patients with pre-existing psoriasis receiving checkpoint inhibitors, 53% of flares were successfully managed with topical therapy alone, and only 7% required immunotherapy discontinuation 3

Grade 2 Flares

Hold nivolumab temporarily and escalate treatment: 1

• Continue high-potency topical corticosteroids and emollients 1
• Initiate oral prednisone 0.5-1 mg/kg daily, tapering over 4 weeks 1
• Monitor weekly for improvement 1
• If no improvement after 4 weeks, regrade as Grade 3 1
• Resume nivolumab once downgraded to Grade 1 and prednisone dose is below 10 mg/day 1

Grade 3 Flares

Hold nivolumab and obtain dermatology consultation to determine appropriateness of resuming: 1

• Initiate oral prednisone 1 mg/kg/day, tapering over at least 4 weeks 1
• Apply high-potency topical corticosteroids 1
• Consider phototherapy for severe pruritus 1
• May resume nivolumab once downgraded to Grade 1 with prednisone below 10 mg/day, but only with close dermatology follow-up 1
• In FDA labeling data, among patients who reinitiated nivolumab after holding for immune-mediated rash, 33% experienced recurrence 2

Critical Decision Point: Continue vs. Discontinue Nivolumab

The decision to continue nivolumab should prioritize cancer mortality over psoriasis morbidity in most cases: 1, 3

• Retrospective data from 76 patients showed progression-free survival was significantly longer in patients who experienced psoriasis flares versus those who did not (39 vs 8.7 months, p=0.049), suggesting flares may indicate effective immune activation 3
• Only 7% of patients required permanent nivolumab discontinuation for psoriasis flares 3
• Among patients who reinitiated nivolumab after temporary hold, 33-53% experienced recurrence depending on combination therapy, but most were manageable 2

Permanent discontinuation is mandatory only for Grade 4 reactions or life-threatening SCAR conditions (Stevens-Johnson Syndrome, TEN, DRESS). 1, 2

Systemic Therapy Considerations for Refractory Flares

If topical therapy and systemic corticosteroids fail to control Grade 2-3 flares, consider adding conventional psoriasis systemic agents while continuing cancer treatment: 4, 3

• 21% of patients with checkpoint inhibitor-induced psoriasis flares required systemic psoriasis therapy beyond corticosteroids 3
• Methotrexate, cyclosporine, or biologics can be considered, but require coordination between oncology and dermatology 4
• Avoid systemic corticosteroids as monotherapy for long-term psoriasis control, as withdrawal can precipitate severe rebound 1, 4

Common Pitfalls to Avoid

Never discontinue nivolumab prematurely for manageable psoriasis flares, as cancer mortality risk far exceeds psoriasis morbidity: 1, 3

• The majority of flares (53%) respond to topical therapy alone 3
• Patients experiencing flares had better cancer outcomes than those without flares 3

Do not use systemic corticosteroids as first-line monotherapy for chronic psoriasis management, even when triggered by immunotherapy: 1, 4

• Systemic corticosteroids can precipitate erythrodermic or generalized pustular psoriasis upon withdrawal 1, 4
• Use corticosteroids only as bridge therapy while initiating topical or other systemic psoriasis treatments 1, 4

Recognize that psoriasis flares from nivolumab typically occur early (median 44 days after initiation) but can be delayed: 3

• Maintain vigilance throughout treatment course 3
• Serial clinical photography can help monitor progression 1

Consider skin biopsy if diagnosis is uncertain or if severe cutaneous adverse reactions are suspected, as management differs dramatically: 1

• SCAR conditions require immediate permanent discontinuation 1
• Psoriasis flares can usually be managed with continued therapy 1, 3