Cryoglobulinemia Type II: Sustained Remission After B-Cell–Directed Therapy

BACKGROUND Cryoglobulinemia is a rare disease with a prevalence of <5 cases per 10 000. In many cases there is significant diagnostic delay, leading to years of morbidity. There are no randomized trials on non-infectious type II cryoglobulinemia, and choice of therapy is based on clinical expertise and observational data. Therapy based on the monoclonal anti-CD20 antibody rituximab in combination with glucocorticosteroids is the preferred choice in many centers. This strategy induces clinical remission in two-thirds of patients. However, one-third of the initially-responding patients experience relapse within the first year. As such, many patients will not achieve sustained remission. CASE REPORT We describe the clinical course of 2 patients with non-infectious type II cryoglobulinemia. They were initially treated according to standard clinical practice, without lasting symptom relief. A novel treatment strategy was attempted, targeting the underlying B-cell clone responsible for the production of disease-inducing monoclonal immunoglobulins. These protocols, initially developed for treatment of chronic cold agglutinin disease, contain rituximab in combination with fludarabine or bendamustine. Sustained clinical, immunological, and hematological remissions were achieved in both patients, and the treatment was well tolerated with no need for hospitalization or other supportive measures. CONCLUSIONS Treating patients with type II cryoglobulinemia using chemo-immune therapy in the same regimens as used in cold agglutinin disease could be considered as a therapeutic option. Based on our observations in the 2 patients described in this case series, this approach seems feasible and well tolerated. Deep sustained remissions may be possible.