Life-threatening Disseminated Enterovirus Infection During Combined Rituximab and Ibrutinib Maintenance Treatment for Mantle Cell Lymphoma

A Case Report

Maximilian Higer; Denis Cana; Juergen Podlech; Simin Schadmand-Fischer; Andreas Schwarting; Daniel Teschner; Matthias Theobald; Thomas Wölfel; Georg Hess


J Med Case Reports. 2020;14(135) 

In This Article


Mantle cell lymphoma (MCL) frequently presents with an aggressive disease course. In consequence, intensive sequential treatment with chemoimmunotherapy induction, high-dose therapy consolidation, and rituximab maintenance has been established as the standard of care for eligible patients; however, patients continue to relapse. Current clinical research strategies test the combination of rituximab and ibrutinib, an inhibitor of Bruton tyrosine kinase (BTK) interacting with the B-cell receptor pathway, in induction and maintenance treatment for MCL. Until now, the toxicity of the long-term combination of these agents has not been well defined. Long-term use of rituximab is usually well tolerated. However, some patients experience sequelae of long-term lymphodepletion, such as reactivation of viruses, including hepatitis B. Ibrutinib has been associated with reduction of humoral immunity and subsequent infections. Moreover, in combination with R-CHOP (rituximab, cyclophosphamide, doxorubicin hydrochloride [hydroxydaunomycin], vincristine sulfate [oncovin], prednisone), an increased toxicity has been noted.[1,2] In this report, we describe a life-threatening enterovirus infection involving multiple organ systems in a patient with MCL during combined rituximab and ibrutinib maintenance therapy.

Enteroviruses are small ribonucleic acid (RNA) viruses and belong to the Picornaviridae family. In immunocompetent individuals, enterovirus infections are usually asymptomatic. If symptoms occur, they usually resemble signs of "common cold" or gastroenteritis. However, even myocarditis, exanthema, encephalomyelitis, or acute paralysis can arise, depending on the virus subtype and immune status of the patient.[3] Moreover, patients with hereditary or acquired B-cell defects may be at risk for persistent, in some cases even fatal, infection.[4]