Hepatitis E virus infections in patients with multiple myeloma: an emerging challenge in the era of immunotherapeutic approaches

Hepatitis E virus (HEV) is an under-recognized cause of viral hepatitis, with rising incidence in high-income countries largely driven by zoonotic transmission. Patients with multiple myeloma are especially vulnerable to HEV, yet recommendations for antiviral treatment and impact on the management of myeloma treatment are missing. Here, we describe seven patients (five males, two females) with multiple myeloma who were diagnosed with HEV infection at a tertiary care center in Western Europe within less than one year. All cases were confirmed by positive HEV-RNA PCR in the peripheral blood. Although no instances of fulminant hepatitis were observed, HEV infection led to substantial treatment delays. Ribavirin was initiated in four cases. The three patients undergoing T-cell redirecting therapies, including one with prior ciltacabtagen autoleucel and two on bispecific antibodies, progressed to chronic HEV infection despite ribavirin treatment. One patient, despite clearing HEV from peripheral blood, developed persistent vertigo and tested positive for HEV-RNA in the cerebrospinal fluid, indicating neuroinvasion. As the largest reported cohort of myeloma patients with HEV infections, this study emphasizes the urgent need to increase awareness of HEV as an emerging threat, refine screening protocols, and establish standardized therapeutic strategies in the era of novel immunotherapeutic approaches.