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

This phase I study evaluated the safety and efficacy of single-agent ibrutinib in Japanese patients with treatment-naïve chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (aged 20-69 years and ineligible for chemotherapy using fludarabine 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-naïve CLL.