Kipps Thomas J, Eradat Herbert, Grosicki Sebastian, Catalano John, Cosolo Walter, Dyagil Iryna S, Yalamanchili Sreeni, Chai Akiko, Sahasranaman Srikumar, Punnoose Elizabeth, Hurst Deborah, Pylypenko Halyna
a Department of Hematology-Oncology , UCSD School of Medicine , San Diego , CA , USA.
b Division of Hematology-Oncology, David Geffen School of Medicine at UCLA , Los Angeles , CA , USA.
Leuk Lymphoma. 2015;56(10):2826-33. doi: 10.3109/10428194.2015.1030638. Epub 2015 May 12.
We evaluated the safety and biologic activity of the BH3 mimetic protein, navitoclax, combined with rituximab, in comparison to rituximab alone. One hundred and eighteen patients with chronic lymphocytic leukemia (CLL) were randomized to receive eight weekly doses of rituximab (arm A), eight weekly doses of rituximab plus daily navitoclax for 12 weeks (arm B) or eight weekly doses of rituximab plus daily navitoclax until disease progression or unacceptable toxicity (arm C). Investigator-assessed overall response rates (complete [CR] and partial [PR]) were 35% (arm A), 55% (arm B, p = 0.19 vs. A) and 70% (arm C, p = 0.0034 vs. A). Patients with del(17p) or high levels of BCL2 had significantly better clinical responses when treated with navitoclax. Navitoclax in combination with rituximab was well tolerated as initial therapy for patients with CLL, yielded higher response rates than rituximab alone and resulted in prolonged progression-free survival with treatment beyond 12 weeks.
我们评估了BH3模拟蛋白维奈托克与利妥昔单抗联合使用时的安全性和生物学活性，并与单独使用利妥昔单抗进行了比较。118例慢性淋巴细胞白血病（CLL）患者被随机分为三组，分别接受8周的利妥昔单抗治疗（A组）、8周的利妥昔单抗加12周每日维奈托克治疗（B组）或8周的利妥昔单抗加每日维奈托克直至疾病进展或出现不可接受的毒性（C组）。研究者评估的总缓解率（完全缓解[CR]和部分缓解[PR]）分别为35%（A组）、55%（B组，与A组相比p = 0.19）和70%（C组，与A组相比p = 0.0034）。伴有del(17p)或高表达BCL2的患者在接受维奈托克治疗时临床缓解明显更好。维奈托克联合利妥昔单抗作为CLL患者的初始治疗耐受性良好，缓解率高于单独使用利妥昔单抗，且治疗超过12周可延长无进展生存期。
