A phase II, single-arm multicenter study of low-dose rituximab for refractory mixed cryoglobulinemia secondary to hepatitis C virus infection

• Published in: Autoimmunity reviews Vol. 10; no. 11; pp. 714 - 719
• Main Authors: Visentini, Marcella, Ludovisi, Serena, Petrarca, Antonio, Pulvirenti, Federica, Zaramella, Marco, Monti, Monica, Conti, Valentina, Ranieri, Jessica, Colantuono, Stefania, Fognani, Elisa, Piluso, Alessia, Tinelli, Carmine, Zignego, Anna Linda, Mondelli, Mario U, Fiorilli, Massimo, Casato, Milvia
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.09.2011
• Subjects: Aged; Aged, 80 and over; Allergy and Immunology; Antibodies, Monoclonal, Murine-Derived - administration & dosage; Antibodies, Monoclonal, Murine-Derived - adverse effects; Antiviral Agents - administration & dosage; Clinical Protocols; Cost-Benefit Analysis; Cryoglobulinemia - drug therapy; Cryoglobulinemia - economics; Cryoglobulinemia - etiology; Cryoglobulinemia - physiopathology; Drug Resistance; Female; Follow-Up Studies; HCV; Hepatitis C - complications; Hepatitis C - drug therapy; Hepatitis C - economics; Hepatitis C - physiopathology; Hepatitis C virus; Humans; Italy; Male; Middle Aged; Mixed cryoglobulinemia; Recurrence; Remission Induction; Rituximab; Italy; Rituximab; HCV; Mixed cryoglobulinemia
• ISSN: 1568-9972; 1568-9972; 1873-0183
• DOI: 10.1016/j.autrev.2011.04.033

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 375 mg/m2 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, 250 mg/m2 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 6.5 months, similar to the 6.7 months 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.