Ibrutinib was shown in an international, multicenter, open-label, phase 2 trial to provide durable responses and to have a favorable safety profile in patients with relapsed or refractory MCL (Wang ML, et al. N Engl J Med. 2013;369:507-516). At ASH 2014, Wang and colleagues presented the updated safety and efficacy results of this phase 2 trial, which had a median follow-up of approximately 27 months (Blood. 2014;124. Abstract 4453).
In this study, 111 patients with relapsed or refractory MCL who had a median of 3 previous therapies received oral ibrutinib 560 mg once daily until disease progression or unacceptable toxicity. Patients were eligible to continue therapy into a long-term extension study if they had stable disease or better.
The investigator-assessed ORR was 67%, with 22.5% of patients experiencing a complete response. The median time to response was 1.9 months, and the median time to a complete response was 5.5 months. The median duration of response was 17.5 months. Among all treated patients, with an estimated median follow-up of 26.7 months, the median PFS was 13 months, and the median OS was 22.5 months. The 24-month Kaplan-Meier PFS and OS rates were 31% and 47%, respectively. The most frequent treatment-emergent AEs included infection, diarrhea, bleeding, fatigue, nausea, and dyspnea. In total, grade ?3 AEs occurred in 81% of the patients, and serious AEs of any grade were seen in 63% of the patients. Treatment discontinuation resulting from AEs was reported in 11% of patients.
These results with a median 27-month follow-up demonstrate the durability of responses and the sustained single-agent activity of continuous ibrutinib in patients with relapsed or refractory MCL. The investigators concluded that ibrutinib continues to show a favorable risk-benefit profile over time, with a safety profile consistent with that reported previously.
