Treatment of myelodysplastic syndromes with excess of blasts by bevacizumab is well tolerated and is associated with a decrease of VEGF plasma level
Treatment of myelodysplastic syndromes with excess of blasts by bevacizumab is well tolerated and is associated with a decrease of VEGF plasma level
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DOI：
10.1007/s00277-011-1242-z
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发表时间：
2012-01-01
影响因子：
3.5
通讯作者：
Dreyfus, Francois
中科院分区：
文献类型：
--
作者：
Legros, Laurence;Slama, Bohrane;Dreyfus, Francois
骨髓增生异常综合征（MDS）与骨髓血管分布增加和各种血管生成因子（包括与白血病细胞增殖和存活有关的血管内皮生长因子（VEGF））水平增加有关。在批准低甲基化药物用于该适应症之前，GFM进行了一项多中心II期试验，测试贝伐单抗（一种抗VEGF的人源化单克隆抗体）在骨髓原始细胞过多的MDS中的疗效和耐受性及其对骨髓血管生成的影响。入组了21名患者（16名男性和5名女性），中位年龄为70岁，其中19名患者在治疗后可评价血液学反应（每2周一次静脉注射5 mg/kg，持续12周）。基线时WHO诊断为RAEB-1（38%）和RAEB-2（62%）。治疗耐受性良好，与VEGF血浆水平[中位数]显著降低相关。（低四分位数-高四分位数）]从65.5 pg/ml [LQ（低四分位数）-HQ（高四分位数），35.3-87.3至30.4 pg/ml（LQ-HQ，22.5-34.0 pg/ml）]（p < 0.01）和骨髓血管生成从中位数20血管/mm（3）减少（LQ-HQ，16.5-33血管/mm（3））至15.5血管/mm（3）（LQ-HQ，10-23.2血管/mm（3））（p = 0.03）。另一方面，仅1例患者出现显著血液学应答，实现了RBC输注独立性。因此，尽管贝伐单抗对我们患者的VEGF水平和血管生成有显著影响，但当这种药物作为单一药物使用时，很少看到反应。然而，鉴于其良好的耐受性，贝伐单抗与其他药物，特别是低甲基化药物的组合，可以考虑在MDS。
Myelodysplastic syndromes (MDS) are associated with increased bone marrow vascularity and increased levels of various angiogenic factors including Vascular Endothelial Growth Factor (VEGF) which is implicated in the proliferation and survival of leukemic cells. Before the approval of hypomethylating agents in this indication, the GFM conducted a multicenter phase II trial testing the efficacy and tolerance of bevacizumab, a humanized monoclonal antibody against VEGF, in MDS with excess of marrow blasts and its impact on bone marrow angiogenesis. Twenty-one patients were enrolled (16 males and five females) with a median age of 70 years and 19 were evaluable for haematological response after treatment (5 mg/kg IV every 2 weeks for 12 weeks). WHO diagnosis at baseline was RAEB-1 (38%) and RAEB-2 (62%). Treatment was well tolerated and was associated with significant decrease of VEGF plasma level [median (low quartile-high quartile)] from 65.5 pg/ml [LQ (low-quartile)-HQ (high quartile), 35.3-87.3 to 30.4 pg/ml (LQ-HQ, 22.5-34.0 pg/ml)] (p < 0.01) and reduction of bone marrow angiogenesis from a median of 20 vessels/mm(3) (LQ-HQ, 16.5-33 vessels/mm(3)) to 15.5 vessels/mm(3) (LQ-HQ, 10-23.2 vessels/mm(3)) (p = 0.03). On the other hand, only one patient had a significant haematological response with achievement of RBC transfusion independence. Thus, although bevacizumab had a significant impact on VEGF levels and angiogenesis in our patients, very few responses were seen when this drug was used as single agent. Given its good tolerability profile, however, combination of bevacizumab with other drugs, especially hypomethylating agents, could be considered in MDS.