Phase I study of ibrutinib in Japanese patients with treatment-naive chronic lymphocytic leukemia/small lymphocytic lymphoma

This phase I study evaluated the safety and efficacy of single-agent ibrutinib in Japanese patients with treatment-naive chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (aged 20-69 years and ineligible for chemotherapy using fludara-bine or cyclophosphamide, or aged >= 70 years). Eight patients received oral ibrutinib 420 mg once daily until progressive disease or unacceptable toxicity. The primary endpoint was safety; secondary endpoints included the overall response rate (ORR). At the time of final analysis (August 22. 2018). eight patients (all with CLL; median age. 68.5 years) had received ibrutinib for a median of 32.2 months (range, 10.4-35.9); all patients had discontinued study treatment. with 50.0% of patients switching to marketing-approved ibrutinib as subsequent anticancer therapy. All patients had >= 1 adverse event (AE); the most common AEs included a decreased platelet count, upper respiratory tract infection, increased lymphocyte count. diarrhea. nasopharyngitis, peripheral edema and rash. Four patients (50.0%) had a total of eight grade >= 3 AEs, most commonly lung infection and decreased neutrophil count. Eight serious AEs were reported in four patients (50.0%); these included a case of muscle hemorrhage (grade 3). decreased neutrophil count (grade 4) that led to dose reduction and one case of fatal cardiac arrest. The ORR was 87.5% (7/8 patients [exact 95% confidence interval 47.3-99.7]). One patient had a complete response. six had a partial response and one had a partial response with lymphocytosis. Ibrutinib had an acceptable safety profile and high ORR in Japanese patients with treatment-naive CLL.