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Ibrutinib monotherapy in chronic lymphoid leukaemia
The Lancet Oncology, Volume 15, Issue 8, July 2014, Pages e312
Ibrutinib, compared with ofatumumab, can substantially improve progression-free survival (PFS), overall survival, and response in patients with previously treated chronic lymphoid leukaemia, according to new research published in the New England Journal of Medicine and presented at ASCO. John Byrd and colleagues presented results from a phase 3 trial comparing the efficacy of ibrutinib (a Bruton-tyrosine-kinase inhibitor) with ofatumumab in patients with relapsed or refractory chronic lymphoid leukaemia or small lymphocytic lymphoma. They randomly assigned 391 patients to receive oral ibrutinib (n=195) or intravenous ofatumumab (n=196). Median follow-up was 9·4 months (range 0·1–16·6). The researchers found that ibrutinib substantially improved PFS in the participants, compared with ofatumumab. Median duration of PFS was not reached in the ibrutinib group (88% of patients were progression free at 6 months) compared with a median of 8·1 months in the ofatumumab group. The hazard ratio for progression or death in the ibrutinib group was 0·22 (95% CI 0·15–0·32; p<0·001). Ibrutinib also substantially improved overall survival (hazard ratio for death 0·43; 95% CI 0·24–0·79; p=0·005), the researchers noted. 83 (43%) of patients treated with ibrutinib had a partial response compared with eight (4%) of those with ofatumumab. The most frequent non-haematological adverse events that occurred in at least 20% of patients included diarrhoea, fatigue, pyrexia, and nausea in the ibrutinib group, and fatigue, infusion-related reactions, and cough in the ofatumumab group.
Thorsten Zenz (National Center for Tumour Diseases, Heidelberg, Germany) says: “The study demonstrates the power of inhibitors of the B cell receptor in chronic lymphoid leukaemia.” The current study as well as previous work by Byrd and colleagues can change the practice in chronic lymphoid leukaemia, Zenz comments.
According to Jason Westin (MD Anderson Cancer Center, TX, USA), the implications of the study's findings will set a new high standard for future trials. He comments: “With these results, it may be challenging for future single agent comparison trials of targeted inhibitors to have sufficient power to show further meaningful improvements without accrual of very large numbers of patients or long follow-up time.”