Cramer Paula, Langerbeins Petra, Hallek Michael
From the *Department I of Internal Medicine, Center of Integrated Oncology Cologne-Bonn and German CLL Study Group, University of Cologne; and †CECAD-Cologne Cluster of Excellence in Cellular Stress Responses in Aging-Associated Diseases, Cologne, Germany.
Cancer J. 2016 Jan-Feb;22(1):62-6. doi: 10.1097/PPO.0000000000000174.
The landscape of treatment for chronic lymphocytic leukemia is rapidly changing at present. Considerable improvement has been achieved with the introduction of the anti-CD20 antibodies, and chemoimmunotherapy has now become an established standard for patients without the high-risk features del(17p)/TP53 mutation. Also, the outcome of patients with these adverse genetic aberrations was dramatically improved with the introduction of the kinase inhibitors ibrutinib and idelalisib. Different combinations of these and additional novel agents are currently evaluated in clinical trials. The combination of the Bruton tyrosine kinase inhibitor ibrutinib with an anti-CD20 antibody is an attractive option, because both drugs act synergistically: ibrutinib redistributes the CLL cells from their homing organs to the peripheral blood, and obinutuzumab eliminates the leukemic cells in the blood with particular efficiency. Adding the Bcl-2 antagonist venetoclax could further intensify the treatment of CLL. This combination might hold the potential to achieve a deep remission with an eradication of residual CLL cells and thus lead to long-term remissions of CLL.
目前，慢性淋巴细胞白血病的治疗格局正在迅速改变。随着抗CD20抗体的引入，已取得了显著进展，对于没有高危特征del(17p)/TP53突变的患者，化疗免疫疗法现已成为既定标准。此外，随着激酶抑制剂依鲁替尼和idelalisib的引入，具有这些不良基因畸变的患者的治疗结果也得到了显著改善。目前正在临床试验中评估这些药物与其他新型药物的不同组合。布鲁顿酪氨酸激酶抑制剂依鲁替尼与抗CD20抗体的联合是一个有吸引力的选择，因为这两种药物具有协同作用：依鲁替尼将慢性淋巴细胞白血病细胞从其归巢器官重新分布到外周血中，而奥滨尤妥珠单抗能特别有效地清除血液中的白血病细胞。添加Bcl-2拮抗剂维奈克拉可能会进一步强化慢性淋巴细胞白血病的治疗。这种联合可能有潜力实现深度缓解，根除残留的慢性淋巴细胞白血病细胞，从而导致慢性淋巴细胞白血病的长期缓解。
