Daobin Zhou1, Wei Xu2, Hongbing Ma3, Chunting Zhao4, Yu Hu5, Yaozhong Zhao6, Depei Wu7, Xielan Zhao8, Yanjuan He8, Jinsong Yan9, Chunsen Wang10, Fanyi Meng11, Jie Jin12, Xiaohong Zhang13, Kang Yu14, Jianda Hu15, Yue Lv16. 1. Department of Hematology, Peking Union Medical College Hospital, Beijing, China. zhoudaobinoffice@163.com. 2. Department of Hematology, Jiangsu Province Hospital, Jiangsu, China. 3. Department of Hematology, West China School of Medicine West China Hospital of Sichuan University, Sichuan, China. 4. Department of Hematology, The Affiliated Hospital of Qingdao University, Qingdao, China. 5. Department of Hematology, Union Hospital Affiliated To Tongji Medical College of Huazhong University, Huazhong, China. 6. Department of Hematology, Hematology Hospital of Chinese Academy of Medical Sciences, Beijing, China. 7. Department of Hematology, The First Affiliated Hospital Of Soochow University, Soochow, China. 8. Department of Hematology, Xiangya Hospital Centeal South University, Xiangya, China. 9. Department of Hematology, The Second Hospital of Dalian Medical University, Dalian, China. 10. Department of Hematology, Sichuan Academy of Medical Sciences, Sichuan Provincial Peoples's Hospital , Sichuan, China. 11. Department of Hematology, Dongguan Kanghua Hospital, Dongguan, China. 12. Department of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang, China. 13. Department of Hematology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang, China. 14. Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China. 15. Department of Hematology, Union Hospital Affiliated to Fujian Medical University, Fujian, China. 16. Department of Hematology, Sun Yat-Sen University Cancer Center, Sun Yat-sen, China.
Abstract
BACKGROUND: Chronic lymphoblastic leukemia (CLL) is the most common adult leukemia and mainly affects the elderly. Chemoimmunotherapy still has a role in the standard frontline therapy for specific population. However, the clinical activity of bendamustine has not been investigated in unfit Chinese patients with CLL. This study aimed to compare the efficacy and safety of bendamustine versus chlorambucil for untreated Chinese patients with Binet stage B/C CLL. METHODS: In this multi-center, randomized, open-label, parallel-controlled, phase III trial, patients with previously untreated CLL were enrolled and randomly assigned (1:1) to receive bendamustine or chlorambucil. The primary endpoint was the objective response rate. Secondary endpoints included progression-free survival, the duration of response, and overall survival. Adverse events were recorded to evaluate safety. RESULTS: Of 158 screened patients, 147 were enrolled and randomly allocated to receive bendamustine (n = 72) or chlorambucil (n = 75). After a median follow-up of 25.6 months (IQR 12.5-27.7), 69.0% (95% CI, 56.9-79.5) of bendamustine-treated patients achieved objective response and 37.0% (95% CI, 26.0-49.1) of chlorambucil with a difference of 32.0% (95%CI: 16.6-47.5), demonstrating the superiority of bendamustine to chlorambucil (p < 0.001). The median progression-free survival was longer for bendamustine (16.5 months; 95% CI, 11.3-24.7) versus chlorambucil (9.6 months; 95% CI, 8.7-11.8; p < 0.001). A longer median duration of response was seen in those receiving bendamustine (19.2 months; 95% CI, 11.8-29.1) than chlorambucil (10.7 months; 95% CI, 5.6-13.6; p = 0.0018). Median overall survival was not reached in either group. Overall survival at 18 months was 88% for bendamustine versus 85% for chlorambucil. Most common adverse events in both groups were neutropenia and thrombocytopenia. CONCLUSION: In untreated Chinese patients with Binet stage B/C CLL, bendamustine induced the better objective response and resulted in longer progression-free survival than chlorambucil. Overall, these results validate the role of bendamustine as an effective and safe first-line therapy in this population.
BACKGROUND: Chronic lymphoblastic leukemia (CLL) is the most common adult leukemia and mainly affects the elderly. Chemoimmunotherapy still has a role in the standard frontline therapy for specific population. However, the clinical activity of bendamustine has not been investigated in unfit Chinese patients with CLL. This study aimed to compare the efficacy and safety of bendamustine versus chlorambucil for untreated Chinese patients with Binet stage B/C CLL. METHODS: In this multi-center, randomized, open-label, parallel-controlled, phase III trial, patients with previously untreated CLL were enrolled and randomly assigned (1:1) to receive bendamustine or chlorambucil. The primary endpoint was the objective response rate. Secondary endpoints included progression-free survival, the duration of response, and overall survival. Adverse events were recorded to evaluate safety. RESULTS: Of 158 screened patients, 147 were enrolled and randomly allocated to receive bendamustine (n = 72) or chlorambucil (n = 75). After a median follow-up of 25.6 months (IQR 12.5-27.7), 69.0% (95% CI, 56.9-79.5) of bendamustine-treated patients achieved objective response and 37.0% (95% CI, 26.0-49.1) of chlorambucil with a difference of 32.0% (95%CI: 16.6-47.5), demonstrating the superiority of bendamustine to chlorambucil (p < 0.001). The median progression-free survival was longer for bendamustine (16.5 months; 95% CI, 11.3-24.7) versus chlorambucil (9.6 months; 95% CI, 8.7-11.8; p < 0.001). A longer median duration of response was seen in those receiving bendamustine (19.2 months; 95% CI, 11.8-29.1) than chlorambucil (10.7 months; 95% CI, 5.6-13.6; p = 0.0018). Median overall survival was not reached in either group. Overall survival at 18 months was 88% for bendamustine versus 85% for chlorambucil. Most common adverse events in both groups were neutropenia and thrombocytopenia. CONCLUSION: In untreated Chinese patients with Binet stage B/C CLL, bendamustine induced the better objective response and resulted in longer progression-free survival than chlorambucil. Overall, these results validate the role of bendamustine as an effective and safe first-line therapy in this population.
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