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Hu5F9-G4阻断CD47联合利妥昔单抗治疗非霍奇金淋巴瘤
CD47 Blockade by Hu5F9-G4 and Rituximab in Non-Hodgkin’s Lymphoma


Ranjana Advani ... 肿瘤 • 2018.11.01
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摘要


背景

Hu5F9-G4(后文称为5F9)抗体是一种能够阻断CD47的巨噬细胞免疫检查点抑制剂,能够诱导对肿瘤细胞的吞噬作用。5F9与利妥昔单抗协同作用,通过增强巨噬细胞介导的抗体依赖性细胞吞噬作用来清除B细胞非霍奇金淋巴瘤细胞。本研究对这种联合疗法进行了临床评估。

 

方法

我们在复发性或难治性非霍奇金淋巴瘤患者中开展了一项1b期研究。患者可能患弥漫性大B细胞淋巴瘤(DLBCL)或滤泡性淋巴瘤。本研究将5F9(起始剂量为1 mg/kg,静脉给药,每周的维持剂量为10~30 mg/kg)与利妥昔单抗一同给药,以确定安全性和疗效,并为2期研究剂量提出建议。

 

结果

本研究总共纳入了22例患者(15例DLBCL和7例滤泡性淋巴瘤)。患者既往接受过的治疗种类中位数为4种(范围,2~10),95%的患者患利妥昔单抗难治性疾病。不良事件主要为1级或2级。最常见的不良事件为贫血和输注相关反应。通过采用包括5F9起始剂量和维持剂量的给药策略,缓解了贫血(一种预期在靶效应[on-target effect])。剂量限制性副作用罕见。所选择的2期研究剂量30 mg/kg 5F9导致对循环白细胞和红细胞达到近100%的CD47受体占用率。总共50%的患者出现客观(即完全或部分)缓解,36%完全缓解。在DLBCL患者中,客观缓解率和完全缓解率分别为40%和33%,在滤泡性淋巴瘤患者中,客观缓解率和完全缓解率分别为71%和43%。DLBCL患者在中位随访6.2个月时,滤泡性淋巴瘤患者在中位随访8.1个月时,91%的缓解仍持续。

 

结论

在侵袭性和惰性淋巴瘤患者中,巨噬细胞检查点抑制剂5F9联合利妥昔单抗治疗显示出有希望的活性。在这项初步研究中未观察到临床上显著的安全性事件(由Forty Seven及白血病和淋巴瘤学会[Leukemia and Lymphoma Society]资助;ClinicalTrials.gov注册号为NCT02953509)。





作者信息

Ranjana Advani, M.D., Ian Flinn, M.D., Ph.D., Leslie Popplewell, M.D., Andres Forero, M.D., Nancy L. Bartlett, M.D., Nilanjan Ghosh, M.D., Ph.D., Justin Kline, M.D., Mark Roschewski, M.D., Ann LaCasce, M.D., Graham P. Collins, M.D., Thu Tran, B.S., Judith Lynn, M.B.A., James Y. Chen, M.D., Ph.D., Jens-Peter Volkmer, M.D., Balaji Agoram, Ph.D., Jie Huang, Sc.D., Ravindra Majeti, M.D., Ph.D., Irving L. Weissman, M.D., Chris H. Takimoto, M.D., Ph.D., Mark P. Chao, M.D., Ph.D., and Sonali M. Smith, M.D.
From Stanford University, Stanford (R.A., T.T., R.M., I.L.W.), City of Hope, Duarte (L.P.), and Forty Seven, Menlo Park (J.L., J.Y.C., J.-P.V., B.A., J.H., R.M., I.L.W., C.H.T., M.P.C.) — all in California; Sarah Cannon Research Institute–Tennessee Oncology, Nashville (I.F.); University of Alabama at Birmingham, Birmingham (A.F.); Washington University in St. Louis, St. Louis (N.L.B.); Levine Cancer Institute–Atrium Health, Charlotte, NC (N.G.); University of Chicago, Chicago (J.K., S.M.S.); National Cancer Institute, Rockville, MD (M.R.); Dana–Farber Cancer Institute, Boston (A.L.); and University of Oxford, Oxford, United Kingdom (G.P.C.). Address reprint requests to Dr. Advani at radvani@stanford.edu.

 

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