Is ritlecitinib (JAK inhibitor) contraindicated in patients with a history of cancer?

Ritlecitinib and History of Cancer: Safety Considerations

Ritlecitinib (a JAK3/TEC family kinase inhibitor) should be used with caution in patients with a history of cancer, particularly those with malignancy diagnosed within the past 5 years, but it is not absolutely contraindicated.

Safety Profile of JAK Inhibitors in Patients with Cancer History

JAK inhibitors as a class require careful consideration in patients with cancer history due to potential risks:

• The European Medicines Agency recommends cautious use of JAK inhibitors as first-line agents in patients with a history of cancer 1
• FDA labeling for JAK inhibitors generally includes warnings about malignancy risk based on safety data from the ORAL Surveillance study, which showed increased cancer risk with tofacitinib compared to TNF inhibitors 1

Specific Considerations for Ritlecitinib

Ritlecitinib's safety profile shows:

• In integrated safety analyses of the ALLEGRO clinical trial program for alopecia areata, malignancies (excluding nonmelanoma skin cancer) occurred at a rate of 0.5% (0.3/100 patient-years) 2
• Long-term safety data through 24 months showed malignancies in only 3 patients out of 449 in the ALLEGRO-LT study 3
• The drug has demonstrated an acceptable safety profile in clinical trials, though these were primarily conducted in alopecia areata patients rather than those with cancer history 2, 4, 3

Decision Algorithm for Ritlecitinib Use in Patients with Cancer History

1. For patients with cancer diagnosed >5 years ago with complete remission:

   • Ritlecitinib may be used with appropriate monitoring
   • Regular skin examinations and cancer surveillance recommended

2. For patients with cancer diagnosed <5 years ago:

   • Consider alternative therapies if available
   • If ritlecitinib is necessary, implement enhanced monitoring:
     • More frequent clinical assessments
     • Regular laboratory monitoring
     • Coordination with oncology team

3. For patients with history of lymphoproliferative disorders or melanoma:

   • Higher risk category - consider alternatives if possible
   • If ritlecitinib is necessary, implement intensive monitoring protocol

Risk Mitigation Strategies

• Baseline cancer screening appropriate for age and risk factors before initiating therapy
• Regular monitoring for signs/symptoms of malignancy during treatment
• Prompt evaluation of any concerning symptoms
• Consider lower dosing (30 mg rather than 50 mg) in high-risk patients, though this may reduce efficacy 5

Important Caveats

• Limited specific data exists on ritlecitinib in patients with cancer history
• Most safety data comes from alopecia areata trials rather than rheumatologic or other inflammatory conditions
• The benefit-risk profile must be carefully assessed for each individual patient
• Monitoring for other JAK inhibitor-associated adverse events (infections, cardiovascular events) remains important

While caution is warranted, the available evidence suggests ritlecitinib can be used in patients with a history of cancer with appropriate risk assessment and monitoring, particularly if the cancer was diagnosed more than 5 years ago and is in complete remission.