Development of Epstein–Barr virus-associated lymphoproliferative disorder and hemophagocytic lymphohistiocytosis during long-term lenalidomide maintenance therapy in multiple myeloma

Reactivation of Epstein–Barr virus (EBV) has been considered a very rare event among patients on immunomodulatory drugs (IMiDs) such as lenalidomide, and an association between the two has not well been recognized. We have recently experienced a rare case of multiple myeloma in which the patient had suffered EBV reactivation during long-term lenalidomide maintenance therapy. The patient subsequently developed EBV-associated lymphoproliferative disease (LPD) as well as EBV-associated hemophagocytic lymphohistiocytosis (EBV–HLH), which was fatal despite intensive treatment. Although rare, clinicians should be aware that such fatal EBV reactivation could occur as a minor yet critical complication of long-term maintenance therapy with IMiDs in multiple myeloma patients. Regular monitoring and early detection of EBV reactivation would be beneficial for these patients, so that proper diagnostic examinations can be initiated without delay. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12185-022-03499-2.