Rituximab-associated infections.
After more than 10 years of use, rituximab has proven to be remarkably safe. However, accumulated evidence now suggests that under some circumstances it may significantly increase the risk of infections. This risk is difficult to quantify because of confounding factors (namely, concomitant use of immunosuppressive or chemotherapeutic agents and underlying conditions), as well as under-reporting. Increased number of infections has been documented in patients treated with maintenance rituximab for low-grade lymphoma and in patients with concomitant severe immunodeficiency, whether caused by human immunodeficiency virus (HIV) infection or immunosuppressive agents like fludarabine. From the practical standpoint, the most important infection is hepatitis B reactivation, which may be delayed and result in fulminant liver failure and death. Special care should be placed on screening for hepatitis B virus (HBV) and preemptive antiviral treatment. Some investigators have reported an increase in Pneumocystis pneumonia. Finally, there is increasing evidence of a possible association with progressive multifocal leukoencephalopathy (PML), a lethal encephalitis caused by the polyomavirus JC. This review enumerates the described infectious complications, summarizes the possible underlying mechanisms of the increased risk, and makes recommendations regarding prevention, diagnosis and management.
Gea-Banacloche
Juan C
JC
Experimental Transplantation and Immunology Branch, National Cancer Institute, Bethesda, MD 20892, USA. banacloj@mail.nih.gov
D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D001327:Autoimmune Diseases / Q000150:complications / Q000188:drug therapy / Q000276:immunology; D004198:Disease Susceptibility; D004769:Enterovirus Infections / Q000209:etiology / Q000821:virology; D006084:Graft Rejection / Q000517:prevention & control; D015658:HIV Infections / Q000150:complications; D006509:Hepatitis B / Q000150:complications / Q000276:immunology; D006515:Hepatitis B virus / Q000276:immunology / Q000502:physiology; D006801:Humans; D016867:Immunocompromised Host; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D007239:Infections / Q000209:etiology* / Q000276:immunology; D007577:JC Virus / Q000276:immunology / Q000502:physiology; D007968:Leukoencephalopathy, Progressive Multifocal / Q000150:complications / Q000276:immunology; D008228:Lymphoma, Non-Hodgkin / Q000150:complications / Q000188:drug therapy / Q000276:immunology; D008590:Meningoencephalitis / Q000276:immunology / Q000821:virology; D016732:Parvovirus B19, Human / Q000276:immunology / Q000502:physiology; D011020:Pneumonia, Pneumocystis / Q000209:etiology; D011183:Postoperative Complications / Q000139:chemically induced / Q000276:immunology; D012307:Risk Factors; D000069283:Rituximab; D014775:Virus Activation / Q000187:drug effects
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D000069283:Rituximab