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

• Published in: Leukemia
• Main Authors: Howard, D R, Munir, T, McParland, L, Rawstron, A C, Milligan, D, Schuh, A, Hockaday, A, Allsup, D J, Marshall, S, Duncombe, A S, O'Dwyer, J L, Smith, A F, Longo, R, Varghese, A, Hillmen, P
• Format: Article in Journal/Newspaper
• Language: unknown
• Published: Nature Publishing Group 2017
• Subjects: WH Haemic and lymphatic systems. Haematology; Arctic
• Online Access: http://www.repository.uhblibrary.co.uk/id/eprint/1569/; https://www.nature.com/articles/leu201796; https://doi.org/10.1038/leu.2017.96

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.