title: A phase II, single-arm multicenter study of low-dose rituximab for refractory mixed cryoglobulinemia secondary to hepatitis C virus infection.
abstract: Eradication of hepatitis C virus (HCV) by antiviral therapy is the treatment of choice for mixed cryoglobulinemia secondary to this infection, but many patients fail to achieve sustained viral responses and need second-line treatments. Several studies have demonstrated that the infusion of the anti-CD20 monoclonal antibody rituximab is highly effective for refractory mixed cryoglobulinemia, with a clinical response in approximately 80% of patients, although the relapse rate is high. Virtually all published studies employed a rituximab dosage of 375mg/m(2) given four times, a schedule used for treating non-Hodgkin's lymphomas. Based on a prior pilot study, we designed a phase II single-arm two-stage study (EUDRACT n. 2008-000086-38) to evaluate the efficacy of a lower dosage of rituximab, 250mg/m(2) given twice, for refractory mixed cryoglobulinemia. We present here the preliminary results in the first 27 patients enrolled. The overall response rate in 24 evaluable patients was 79%, and the mean time to relapse was 6.5months, similar to the 6.7months reported in studies with high-dose rituximab. Side effects were comparable to those seen in patients treated with high-dose. Increase of HCV viral load, reported in some high-dose studies, was not observed in our patients. Low-dose rituximab may provide a more cost/effective and possibly safer alternative for treating refractory HCV-associated mixed cryoglobulinemia.
authors.affiliation: Department of Clinical Immunology, Sapienza University of Rome, Italy. marcella.visentini@uniroma1.it
authors.forename: Marcella
authors.initials: M
authors.lastname: Visentini
authors.forename: Serena
authors.initials: S
authors.lastname: Ludovisi
authors.forename: Antonio
authors.initials: A
authors.lastname: Petrarca
authors.forename: Federica
authors.initials: F
authors.lastname: Pulvirenti
authors.forename: Marco
authors.initials: M
authors.lastname: Zaramella
authors.forename: Monica
authors.initials: M
authors.lastname: Monti
authors.forename: Valentina
authors.initials: V
authors.lastname: Conti
authors.forename: Jessica
authors.initials: J
authors.lastname: Ranieri
authors.forename: Stefania
authors.initials: S
authors.lastname: Colantuono
authors.forename: Elisa
authors.initials: E
authors.lastname: Fognani
authors.forename: Alessia
authors.initials: A
authors.lastname: Piluso
authors.forename: Carmine
authors.initials: C
authors.lastname: Tinelli
authors.forename: Anna Linda
authors.initials: AL
authors.lastname: Zignego
authors.forename: Mario U
authors.initials: MU
authors.lastname: Mondelli
authors.forename: Massimo
authors.initials: M
authors.lastname: Fiorilli
authors.forename: Milvia
authors.initials: M
authors.lastname: Casato
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage* / Q000009:adverse effects; D000998:Antiviral Agents / Q000008:administration & dosage; D002985:Clinical Protocols; D003362:Cost-Benefit Analysis; D003449:Cryoglobulinemia / Q000188:drug therapy* / Q000191:economics / Q000209:etiology / Q000503:physiopathology; D004351:Drug Resistance; D005260:Female; D005500:Follow-Up Studies; D006526:Hepatitis C / Q000150:complications / Q000188:drug therapy* / Q000191:economics / Q000503:physiopathology; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D012074:Remission Induction; D000069283:Rituximab
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000998:Antiviral Agents; D000069283:Rituximab