Phase III Clinical Trial Results Released! Li Jianyong/Qiu Lugui’s Team Publishes Paper on STTT: Orelabrutinib Significantly Superior to Chemoimmunoassay as First-Line Treatment for Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma – Tencent News

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Published on July 8,2026, at 17: 07 on the official account of Shanghai Translational Medicine Network This Phase III clinical trial, NCT04578613, enrolled 192 eligible treatment-naïve CLL/SLL patients, who were randomly assigned 1: 1 to either the orelabrutinib monotherapy group (n=91) or the chlorambucil plus rituximab group (n=101). As of the data cutoff date of May 17,2024, the median follow-up time was 21.4 months. Results showed that, regarding the primary endpoint—progression-free survival (PFS)—assessed by an independent review committee, the median PFS in the orelabrutinib group had not yet been reached, while it was only 19.4 months in the control group. Orelabrutinib significantly reduced the risk of disease progression or death by 68%, crossing the pre-specified efficacy boundary. In terms of 12-month and 24-month PFS rates, the orelabrutinib group achieved rates of 93.1% and 81.6%, respectively, compared to only 76.1% and 48.4% in the control group. This significant early and sustained separation of the benefit curves demonstrates that orelabrutinib can achieve rapid and durable disease control. Notably, orelabrutinib showed consistent superiority in multiple high-risk subgroup analyses—including elderly patients, Rai stage III/IV patients, patients with large tumors, del(11q) positive patients, and patients without IGHV mutation status. In terms of overall response rate (ORR), the orelabrutinib group achieved 90.1%, significantly higher than the control group's 79.2%. Furthermore, the median duration of response in the orelabrutinib group was not yet reached, compared to 19.4 months in the control group, meaning orelabrutinib prolonged the duration of response by 70%. Regarding overall survival (OS), although data are still immature, a trend favorable to orelabrutinib has been observed. The 3-year OS rate in the orelabrutinib group was 92.1%, compared to 78.7% in the control group. In terms of safety, orelabrutinib demonstrated remarkable advantages. Although the median treatment duration in the orelabrutinib group (19.3 months) was almost four times that of the control group (approximately 5 months), the incidence of ≥ grade 3 treatment-related adverse events was only 35.2%, significantly lower than the 60.2% in the control group. Importantly, no off-target toxicities common to BTK inhibitors, such as atrial fibrillation/flutter, serious bleeding, or secondary malignancies, were observed in the study. Treatment-related hematologic toxicities were also significantly lower in the orelabrutinib group than in the control group, with the incidence of neutropenia being 7.7% and 30.6%, respectively. The discontinuation rate due to treatment-related adverse events was only 1.1% in the orelabrutinib group, compared to 6.1% in the control group, further confirming the good tolerability of orelabrutinib. These results from the Phase III study are encouraging. Orelabrutinib not only surpasses traditional chemoimmunotherapy in overall efficacy, but more importantly, it achieves the ideal treatment goal of high efficacy and low toxicity. This breakthrough is particularly significant for elderly patients and high-risk groups. As a second-generation BTK inhibitor, orelabrutinib exhibits higher BTK selectivity and near-complete, sustained BTK occupancy for up to 24 hours, which may be the pharmacological basis for its rapid disease control and excellent safety profile. https: //www. nature. com/articles/s41392-026-02818-x Duration of response and overall survival in the intention-to-treat population as assessed by an independent review committee. Recently, the team led by Li Jianyong from Jiangsu Provincial People's Hospital and Qiu Lugui from the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences, published the results of a multicenter phase III randomized controlled trial in the internationally renowned journal *Signal Transduction and Targeted Therapy* (IF: 81.2). This study confirmed that the new generation of highly selective BTK inhibitor orelabrutinib is significantly more effective than traditional chemoimmunotherapy in newly diagnosed patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), with good safety profile, providing a new, highly effective, and low-toxicity first-line treatment option for these patients.