Impacts of early therapy response, interval to therapy interruption, and cumulative therapy interruption duration on outcome of ibrutinib therapy in relapsed/refractory chronic lymphocytic leukemia.

ABSTRACT

To investigate the impact of early response and treatment interruption on the survival of patients with relapsed/refractory chronic lymphocytic leukemia or small lymphocytic lymphoma (r/r CLL/SLL) treated with ibrutinib. This post hoc analysis used data of patients received ibrutinib treatment from an open-label, multicenter phase 3 study comparing ibrutinib with rituximab in patients with r/r CLL/SLL. The association of complete or partial response at 6 months, interruption within the first 6 months, cumulative interruption durations during the ibrutinib-treated period with progression-free survival (PFS) and overall survival (OS) were evaluated using the adjusted Cox hazard proportional model. The study included 87 patients treated with ibrutinib, of which 74 patients had at least 6 months of ibrutinib treatment and were analyzed. The response at 6 months did not affect PFS (HR = 0.58, 95%CI 0.22-1.49) or OS (HR = 0.86, 95%CI 0.22-3.31). The onset of interruption before or after 6 months was not associated with PFS (HR = 0.88, 95%CI 0.34-2.30) or OS (HR = 0.75, 95%CI 0.23-2.52). However, a cumulative interruption of more than 35 days was independently associated with worse PFS (HR = 2.4, 95%CI 0.99-5.74) and OS (HR = 2.6, 95%CI 0.88-7.44). Continuous interruption for more than 14 days was associated with a numerically lower 3-year PFS rate (> 14 vs. ≤ 14 days 42% vs. 73%) and 3-year OS rate (> 14 vs. ≤ 14 days 58% vs. 84%, both P > 0.05). Response status at 6 months or early therapy interruptions did not affect survival in patients with r/r CLL/SLL treated with ibrutinib. However, a cumulative temporary interruption of more than 35 days could potentially impact patient outcomes.