Reports of hepatosplenic T-cell lymphoma in patients taking tumor necrosis factor blockers, azathioprine, mercaptopurine continue

July 1, 2011

According to a new safety communication recently released by FDA, the agency is continuing to receive reports of a rare but aggressive white blood cell cancer often referred to as hepatosplenic T-cell lymphoma in patients receiving tumor necrosis factor blockers, azathioprine, and mercaptopurine.

Key Points

According to a new safety communication recently released by FDA, the agency is continuing to receive reports of a rare but aggressive white blood cell cancer often referred to as hepatosplenic T-cell lymphoma (HSTCL) in patients receiving tumor necrosis factor (TNF) blockers (including infliximab, etanercept, adalimumab, certolizumab pegol, and golimumab), azathioprine, and mercaptopurine.

Prior to this safety communication, FDA reviewed data from the Adverse Event Reporting System (AERS) database, the medical literature, and the HSTCL Cancer Survivors' Network in order to identify cases of HSTCL associated with the use of TNF blockers, azathioprine, mercaptopurine, or their combination. From the first approval of a TNF blocker through the end of 2010, the agency identified a total of 43 cases of HSTCL linked to the use of these drugs.

Synthesis of the data suggested the majority of cases of HSTCL occurred in patients treated with a combination of these immunosuppressive agents; however, cases of HSTCL have been reported in patients receiving azathioprine or mercaptopurine alone. In regard to TNF blockers, infliximab, adalimumab, or the combination of the 2 were linked to the greatest number of cases (27 cases), although in many of these cases patients were also receiving azathioprine or mercaptopurine concomitantly. To date, no cases of HSTCL have been reported with the TNF blockers certolizumab or golimumab.

FDA previously warned the public of an increased risk of lymphoma with the use of TNF blockers. At that time, warnings were added to the prescribing information of these products.

The Agency noted product labels for infliximab and adalimumab have already been updated and the product labels for azathioprine and mercaptopurine will be updated to include warnings about HSTCL.