Do Ibrutinib Dose Modifications Affect Long-Term Benefits in CLL?
Posted: Tuesday, August 6, 2019
According to research published in Blood, clinically indicated ibrutinib dose reductions or interruptions do not seem to compromise the long-term survival benefits for patients with chronic lymphocytic leukemia (CLL). However, the investigators noted that maintaining high dose intensity is important, and they avoided any unnecessary dose interruptions throughout the study, particularly during the first 6 months of therapy.
“In clinical practice, ibrutinib dose modifications are often medically indicated, either to mitigate clinically significant adverse events (grade 3 or higher, including serious adverse events requiring hospitalizations or urgent medical interventions) or as precautionary drug holds for invasive procedures,” noted Inhye E. Ahn, MD, of the National Institute of Health, and colleagues.
The study included 84 patients with CLL who had either undergone no prior treatment (n = 52) or were considered to have relapsed or refractory disease (n = 32). At a median follow-up of 5.1 years, 75 patients (89.3%) had missed at least 1 dose of ibrutinib, with 57 (67.9%) missing at least 8 consecutive days and 40 (47.6%) missing at least 15 consecutive days. A total of 12 patients (14.3%) underwent permanent dose reductions of varying degrees.
The most common reason for permanent dose reduction was atrial fibrillation (n = 5). Overall, 23 patients (27.4%) experienced disease progression, and 18 patients died. Progression-free survival at 5 years was 64.6% for the entire study and 72.1% for patients missing at least 8 consecutive days of ibrutinib; overall survival at 5 years for the same groups was 79.6% and 90.1%, respectively.
All patients began a treatment regimen of 420 mg of ibrutinib daily. Dose interruptions were tallied based on documented patient history, whereas noncompliance data came from self-reporting. Dose reductions occurred at the request of the researchers.
Disclosure: The study authors’ disclosure information can be found at bloodjournal.org.