# Efficacy and safety of fixed-duration venetoclax plus obinutuzumab in untreated Japanese CLL and SLL: a phase 2 study

## TL;DR

A 12-cycle treatment of venetoclax plus obinutuzumab showed high effectiveness and acceptable safety in Japanese patients with untreated CLL or SLL.

## Contribution

Demonstrates the efficacy and safety of a fixed-duration regimen of venetoclax plus obinutuzumab in Japanese patients with untreated CLL/SLL.

## Key findings

- The CR/CRi rate was 90.0% in patients treated with venetoclax plus obinutuzumab.
- All patients experienced treatment-emergent adverse events, but the safety profile was manageable.
- Common adverse events included infusion-related reactions, decreased neutrophil count, and nausea.

## Abstract

This phase 2 study (NCT05105841) evaluated the safety and efficacy of a fixed-duration 12-cycle regimen of venetoclax plus obinutuzumab in Japanese patients with previously untreated chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). The primary efficacy endpoint was the complete remission (CR)/complete remission with incomplete marrow recovery (CRi) rate, assessed by an independent review committee (IRC) according to the 2008 International Workshop on CLL criteria. Ten patients (6 male, 4 female; 9 CLL, 1 SLL) with a median age of 69.5 years (range 52–76) received venetoclax for a median duration of 11.3 months (range 9.2–12.4). The IRC-assessed CR/CRi rate based on the best overall response was 90.0% (95% confidence interval 55.5%, 99.7%). All patients experienced at least one treatment-emergent adverse event (TEAE), and three patients (30.0%) experienced at least one serious TEAE. The most common TEAEs included infusion-related reactions (60.0%), decreased neutrophil count (50.0%), and nausea (40.0%). Nine patients (90.0%) experienced TEAEs related to venetoclax, while all ten patients (100.0%) had TEAEs related to obinutuzumab. One patient (10.0%) developed COVID-19 pneumonia, necessitating the discontinuation of venetoclax. These findings demonstrate the high efficacy and manageable safety profile of venetoclax plus obinutuzumab in this patient population.

The online version contains supplementary material available at 10.1007/s12185-025-04095-w.