Should infliximab (Infliximab) be stopped in a patient who develops low-grade lymphoma while on the medication?

Management of Infliximab in a Patient with Low-Grade Lymphoma

Infliximab should be discontinued in a patient who develops low-grade lymphoma while on the medication due to the potential risk of worsening the lymphoma and the established association between TNF inhibitors and lymphoproliferative disorders. 1

Rationale for Discontinuation

• TNF inhibitors, including infliximab, carry warnings regarding malignancies, with specific concerns about lymphomas in patients receiving these medications 1
• The FDA label for infliximab explicitly states that in clinical trials, more cases of lymphoma have been observed among patients receiving TNF blockers compared with control patients 1
• Lymphoma rates in patients treated with infliximab are approximately three to four-fold higher than expected in the general population 1
• Caution is recommended when using infliximab in patients with a history of malignancy, which would apply to patients who develop malignancy while on therapy 2

Evidence Supporting Discontinuation

• The FDA drug label warns that patients with inflammatory conditions, particularly those with highly active disease and/or chronic exposure to immunosuppressants, may be at higher risk for lymphoma development 1
• Cases of lymphoma have been reported in patients treated with infliximab monotherapy, including in pediatric-onset inflammatory bowel disease patients 3
• While some lymphomas may be associated with combination therapy (especially with thiopurines), there are documented cases with infliximab alone 3
• British Association of Dermatologists' guidelines recommend avoiding biologic therapy in patients with current or recent history of malignancy 2

Risk Assessment

• The risk of lymphoma with TNF inhibitor therapy appears to be increased compared to the general population 1, 2
• The British Society of Gastroenterology guidelines note that anti-TNF monotherapy has been associated with an increased incidence rate ratio for lymphoma of 2.23 (95% CI 1.79 to 2.79) 2
• A French National cohort study found an increased risk of lymphoma with exposure to anti-TNF monotherapy with an adjusted hazard ratio of 2.41 (95% CI 1.60 to 3.64) 2
• Continuing infliximab in a patient with established lymphoma could potentially interfere with lymphoma treatment or monitoring 1

Alternative Management Options

• After discontinuation of infliximab, consider alternative treatment options for the underlying condition that do not involve TNF inhibitors 2
• In some cases where TNF inhibitors are discontinued due to lymphoma, other biologics with different mechanisms of action may be considered after lymphoma treatment is complete 4
• For inflammatory bowel disease, consider non-TNF biologics such as ustekinumab, which has been used successfully in a case of a patient with previous lymphoma 4
• For rheumatologic conditions, rituximab may be considered for certain conditions after lymphoma treatment, as it is used in both rheumatologic conditions and lymphoma treatment 2

Monitoring and Follow-up

• After discontinuation of infliximab, the patient should be referred to hematology/oncology for comprehensive evaluation and management of the lymphoma 2
• The lymphoma should be classified according to WHO criteria, and therapy should be individualized based on the specific histological subtype 2
• Close monitoring for worsening of the underlying inflammatory condition will be necessary after discontinuation of infliximab 2
• Regular comprehensive dermatological examinations are recommended for patients with a history of biologic therapy, as skin cancers may also be associated with these treatments 2

Special Considerations

• If the patient has inflammatory bowel disease and was receiving combination therapy with thiopurines, both medications should be discontinued due to the particularly high risk of hepatosplenic T-cell lymphoma with this combination 1, 2
• In rare cases where the benefit of continuing anti-TNF therapy might outweigh the risks, this decision should only be made after consultation with oncology and with careful informed consent from the patient 2
• Some low-grade lymphomas may be managed with a watchful waiting approach, but the presence of active anti-TNF therapy complicates this approach 2