Results of the randomized phase IIB ARCTIC trial of low-dose rituximab in previously untreated CLL

• DOI: 10.1038/leu.2017.96
• Publication Date: 2017-03-24T07:41:10Z
• Authors: D R Howard; T Munir; L McParland; A C Rawstron; D Milligan; A Schuh; A Hockaday; D J Allsup; S Marshall; A S Duncombe; J L O'Dwyer; A F Smith; R Longo; A Varghese; P Hillmen
• Keywords: Adult; Aged, 80 and over; Male; 0301 basic medicine; Cancer Research; Dose-Response Relationship, Drug; 610; Antineoplastic Agents; Hematology; Middle Aged; Leukemia, Lymphocytic, Chronic, B-Cell; Survival Analysis; 3. Good health; 03 medical and health sciences; Anesthesiology and Pain Medicine; Costs and Cost Analysis; Humans; Female; Rituximab; Aged

ARCTIC was a multicenter, randomized-controlled, open, phase IIB non-inferiority trial in previously untreated chronic lymphocytic leukemia (CLL). Conventional frontline therapy in fit patients is fludarabine, cyclophosphamide and rituximab (FCR). The trial hypothesized that including mitoxantrone with low-dose rituximab (FCM-miniR) would be non-inferior to FCR. A total of 200 patients were recruited to assess the primary end point of complete remission (CR) rates according to IWCLL criteria. Secondary end points were progression-free survival (PFS), overall survival (OS), overall response rate, minimal residual disease (MRD) negativity, safety and cost-effectiveness. The trial closed following a pre-planned interim analysis. At final analysis, CR rates were 76 FCR vs 55% FCM-miniR (adjusted odds ratio: 0.37; 95% confidence interval: 0.19-0.73). MRD-negativity rates were 54 FCR vs 44% FCM-miniR. More participants experienced serious adverse reactions with FCM-miniR (49%) compared to FCR (41%). There are no significant differences between the treatment groups for PFS and OS. FCM-miniR is not expected to be cost-effective over a lifetime horizon. In summary, FCM-miniR is less well tolerated than FCR with an inferior response and MRD-negativity rate and increased toxicity, and will not be taken forward into a confirmatory trial. The trial demonstrated that oral FCR yields high response rates compared to historical series with intravenous chemotherapy.