Kittai Adam S, Lunning Matthew, Danilov Alexey V
Knight Cancer Institute, Oregon Health & Science University, 2720 SW Moody Ave, #2106, Portland, OR, 97201, USA.
Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Curr Hematol Malig Rep. 2019 Aug;14(4):302-309. doi: 10.1007/s11899-019-00511-1.
Clinicians continue to utilize prognostic biomarkers, such as expression of CD38 and ZAP-70, IGHV mutational status, cytogenetic abnormalities, and genomic aberrations in TP53, to guide prognosis and treatment of patients with CLL. These biomarkers have been validated with standard chemoimmunotherapy. Here, we discuss whether these biomarkers maintain their prognostic significance in the era of targeted therapy.
Multiple phase 3 clinical trials have now proven improved efficacy of targeted therapy over traditional chemoimmunotherapy. We now have ample prospective data using targeted therapy to critically evaluate whether prior prognostic biomarkers remain relevant. High-risk features do not have the same magnitude of effect on clinical outcomes in the era of targeted therapy when compared to chemoimmunotherapy. Aberrations in TP53 continue to predict inferior outcomes. More research is needed to determine what features confer poor prognosis when targeted therapy is used to treat CLL.
临床医生继续使用预后生物标志物，如CD38和ZAP-70的表达、IGHV突变状态、细胞遗传学异常以及TP53基因畸变，来指导慢性淋巴细胞白血病（CLL）患者的预后和治疗。这些生物标志物已在标准化学免疫疗法中得到验证。在此，我们讨论这些生物标志物在靶向治疗时代是否仍保持其预后意义。
多项3期临床试验现已证明靶向治疗比传统化学免疫疗法疗效更佳。我们现在有充足的前瞻性数据，利用靶向治疗来严格评估先前的预后生物标志物是否仍然相关。与化学免疫疗法相比，在靶向治疗时代，高危特征对临床结局的影响程度不同。TP53基因畸变继续预示不良结局。需要更多研究来确定在使用靶向治疗CLL时，哪些特征会导致预后不良。
