Holkova Beata, Shafer Danielle, Yazbeck Victor, Dave Sandeep, Bose Prithviraj, Tombes Mary Beth, Shrader Ellen, Wan Wen, Bandyopadhyay Dipankar, Weir Caryn, Collins Elizabeth B, Garnett Amanda, Kmieciak Maciej, Roberts John D, Garcia-Manero Guillermo, Grant Steven
Massey Cancer Center, Virginia Commonwealth University, Richmond, VA, USA.
Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA, USA.
Leuk Lymphoma. 2021 May;62(5):1187-1194. doi: 10.1080/10428194.2020.1861270. Epub 2020 Dec 28.
We report the results of a phase 1 dose-escalation study of belinostat and bortezomib in adult patients with acute leukemia or MDS or CML with blast crisis. Thirty-eight patients received IV belinostat days 1-5 and 8-12 with IV bortezomib days 1, 4, 8, and 11 every 21 days. QTc prolongation was the only identified DLT. The RP2Ds were 1.3 mg/m bortezomib and 1000 mg/m belinostat. One patient with highly refractory rearranged biphenotypic AML with multiple karyotypic aberrations had a complete pathologic and karyotypic response. One patient with post-MPN AML remained on study with stable disease (SD) for 32 cycles. Whole-exome sequencing revealed no aberrations in the first patient and a hyper-mutator genotype in the second. Eighteen patients had a best response of SD. We conclude that this treatment strategy is feasible but has limited activity in this population. Nevertheless, the factors that predict exceptional responses to this strategy warrant further investigation.
我们报告了一项关于贝利司他和硼替佐米在急性白血病、骨髓增生异常综合征（MDS）或伴有原始细胞危象的慢性粒细胞白血病（CML）成年患者中的1期剂量递增研究结果。38例患者每21天接受第1 - 5天和第8 - 12天静脉注射贝利司他，并在第1、4、8和11天静脉注射硼替佐米。QTc间期延长是唯一确定的剂量限制性毒性（DLT）。推荐的2期剂量（RP2D）为硼替佐米1.3mg/m²和贝利司他1000mg/m²。1例患有高度难治性、伴有多种核型异常的重排双表型急性髓细胞白血病（AML）患者出现了完全病理和核型缓解。1例骨髓增殖性肿瘤（MPN）后急性髓系白血病患者在研究中病情稳定（SD）达32个周期。全外显子测序显示，第一例患者无异常，第二例患者为高突变基因型。18例患者的最佳反应为病情稳定。我们得出结论，这种治疗策略是可行的，但在该人群中的活性有限。然而，预测对该策略有特殊反应的因素值得进一步研究。
