# A phase 2 study of ibrutinib with venetoclax in Japanese patients with untreated CLL and SLL

## TL;DR

This study shows that combining ibrutinib and venetoclax is effective and safe for treating untreated CLL/SLL in Japanese patients.

## Contribution

The study provides new evidence on the efficacy and safety of ibrutinib plus venetoclax in Japanese patients with untreated CLL/SLL.

## Key findings

- The CR/CRi rate was 60.0%, meeting the primary efficacy endpoint.
- 60.0% of patients achieved undetectable measurable residual disease.
- Treatment-emergent adverse events were reported in all patients, but the safety profile was manageable.

## Abstract

The development of effective and safe therapies for chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) in Japan remains a key focus of research. We conducted a phase 2, open-label, multicenter, non-comparative study to evaluate the safety and efficacy of fixed-duration venetoclax plus ibrutinib in 10 patients with previously untreated CLL/SLL (7 CLL/3 SLL). The primary endpoint was the rate of complete remission (CR)/CR with incomplete marrow recovery (CRi) assessed by the independent review committee (IRC). The median age was 72.5 (range 61–77) years. The IRC-assessed CR/CRi rate was 60.0% (95% confidence interval: 26.2–87.8%), exceeding the pre-specified efficacy threshold of 10% and meeting the primary endpoint. The median venetoclax treatment duration was 11.0 (range 2.1–17.7) months. At a median follow-up of 20.6 months, the secondary endpoints of median progression-free and overall survival were not estimated. The overall undetectable measurable residual disease rate was 60.0%. All patients experienced treatment-emergent adverse events (TEAEs), including 7 (70.0%) with grade 3/4 and 2 (20.0%) with serious TEAEs, respectively, and 1 discontinued venetoclax because of a TEAE (increased blood creatine phosphokinase). These findings suggest that venetoclax plus ibrutinib has a favorable benefit–risk profile with high efficacy and manageable safety.