Bendamustine plus rituximab for chronic cold agglutinin disease: results of a Nordic prospective multicenter trial

• Published in: Blood Vol. 130; no. 4; pp. 537 - 541
• Main Authors: Berentsen, Sigbjørn, Randen, Ulla, Oksman, Markku, Birgens, Henrik, Tvedt, Tor Henrik Anderson, Dalgaard, Jakob, Galteland, Eivind, Haukås, Einar, Brudevold, Robert, Sørbø, Jon Hjalmar, Næss, Inger Anne, Malecka, Agnieszka, Tjønnfjord, Geir E.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 27.07.2017
• Subjects: Aged; Aged, 80 and over; Anemia, Hemolytic, Autoimmune - blood; Anemia, Hemolytic, Autoimmune - drug therapy; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Bendamustine Hydrochloride - administration & dosage; Chronic Disease; Europe; Female; Hemoglobins - metabolism; Humans; Male; Middle Aged; Prospective Studies; Rituximab - administration & dosage; Vidarabine - administration & dosage; Vidarabine - analogs & derivatives
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2017-04-778175

Primary chronic cold agglutinin disease (CAD) is a well-defined clinicopathologic entity in which a bone marrow clonal B-cell lymphoproliferation results in autoimmune hemolytic anemia and cold-induced circulatory symptoms. Rituximab monotherapy and fludarabine-rituximab in combination are documented treatment options. In a prospective, nonrandomized multicenter trial, 45 eligible patients received rituximab 375 mg/m2 day 1 and bendamustine 90 mg/m2 days 1 and 2 for 4 cycles at a 28-day interval. Thirty-two patients (71%) responded; 18 (40%) achieved complete response (CR) and 14 (31%) partial response (PR). Among 14 patients previously treated with rituximab or fludarabine-rituximab, 7 (50%) responded to bendamustine-rituximab (3 CR and 4 PR). Hemoglobin levels increased by a median of 4.4 g/dL in the complete responders, 3.9 g/dL in those achieving PR, and 3.7 g/dL in the whole cohort. The 10th percentile of response duration was not reached after 32 months. Grade 3-4 neutropenia occurred in 15 patients (33%), but only 5 (11%) experienced infection with or without neutropenia. Thirteen patients (29%) had their dose of bendamustine reduced. In conclusion, bendamustine-rituximab combination therapy is highly efficient, sufficiently safe, and may be considered in first line for patients with CAD requiring therapy. The trial was registered at www.clinicaltrials.gov as #NCT02689986. •Bendamustine-rituximab therapy results in high overall and CR rates with sustained remissions in CAD.•Bendamustine plus rituximab may be considered in first line for most patients with CAD requiring therapy.