Systematic review: hepatosplenic T‐cell lymphoma on biologic therapy for inflammatory bowel disease, including data from the Food and Drug Administration Adverse Event Reporting System

Abstract

Background:Hepatosplenic T-cell lymphoma (HSTCL) is a rare, poorly treatable malignancy associated with therapy for IBD. Current knowledge of HSTCL risk in IBD comes from an era of step-up therapy, before earlier use of biologics or combination therapy was advocated to achieve deep mucosal healing. HSTCL risk among newer biologic classes has also not been evaluated. Aims:To systematically characterise the association of HSTCL with biologic therapy for IBD. Methods: We conducted a literature search and query of the Food and DrugAdministration Adverse Event Reporting System to summarise HSTCL cases among IBD patients with prior biologic exposure. Demographics and immunosuppression exposure were extracted. Patients were stratified by current regimen (combination therapy, biologic monotherapy or no biologic), and biologic class (anti-TNF, antiintegrin, anti-interleukin 12/23).Results: Sixty-two cases of HSTCL were identified from 2486 abstracts and 181 FDA Adverse Events Reporting System reports. The median age of affected patients was 28 years (range 12-81), and 83.6% were male, 84.7% had Crohn's disease. Five of 62 patients had no reported azathioprine/mercaptopurine exposure. Three patients within the cohort developed HSTCL after exposure to natalizumab, vedolizumab or ustekinumab; all three also had anti-TNF and azathioprine/mercaptopurine exposure.Forty-three of 49 (87.8%) patients with known outcomes died with a median survival of 5 months.Conclusions: Consistent with existing data, almost all identified HSTCL cases among IBD patients on biologic therapy had azathioprine/mercaptopurine exposure, and all cases on patients exposed to biologics had anti-TNF exposure. These data suggest initiating a patient-centred discussion before starting anti-TNF therapy or other biologics.

<p>Risk of Lymphoma Associated with Anti-TNF Therapy in Patients with Inflammatory Bowel Disease: Implications for Therapy</p>

“…The authors argued that, despite the appreciated correlation with TP use, there still may be an associated risk with ATA. 39 …”

“…While HSTCL is a serious illness with poor outcomes, the rarity of developing this malignancy should be weighed against the higher risk of worsening or uncontrolled IBD when considering ATA therapy. 39 …”

“…36 A 2020 study also examined data from the FDA AERS database. 39 Patients were divided into combination therapy, biologic monotherapy, or no biologic therapy groups. Sixty-two cases of HSTCL were identified from 2002 to 2017 with the majority of patients being male (83.6%), young (median age 28 (range 12-81)), and having Crohn's disease (84.7%).…”

“…The authors argued that, despite the appreciated correlation with TP use, there still may be an associated risk with ATA. 39 The study also assessed the role of EBV in HSTCL development. Only 4 of the 62 cases were found to have active EBV infection.…”

Evolving Role of Thiopurines in Inflammatory Bowel Disease in the Era of Biologics and New Small Molecules

“…This lymphoma is not EBV related; however, it also most commonly affects men < 35 years [67]. Although cases have been identified in patients treated only with biologic therapy, hepatosplenic T-cell lymphoma typically occurs in patients treated with combination anti-TNF agents and thiopurines for > 2 years [67,68]. Therefore, it is recommended to limit combination therapy beyond 2 years in this patient group where possible.…”