Division of Hematology, University of Utah, Blood/Marrow Transplant and Myeloma Program, Salt Lake City, UT, USA.
Eur J Haematol. 2011 Jun;86(6):484-7. doi: 10.1111/j.1600-0609.2011.01602.x.
The ubiquitin-proteasome pathway regulates bone formation through osteoblast differentiation. We analyzed variation alkaline phosphatase (ALP) during carfilzomib treatment. Data from 38 patients enrolled in the PX-171-003 and 29 patients in PX-171-004 studies, for patients with relapsed/refractory myeloma, were analyzed. All patients received 20 mg/m(2) of carfilzomib on Days 1, 2, 8, 9, 15, and 16 of a 28-day cycle. Sixty-seven patients from ALP data were evaluable. In PX-171-003, the ORR (>PR) was 18% and the clinical benefit response (CBR; >MR) was 26%, while in PX-171-004, the ORR was 35.5% overall and 57% in bortezomib-naive patients. ALP increment from baseline was statistically different in patients who achieved ≥ VGPR compared with all others on Days 1 (P = 0.0049) and 8 (P = 0.006) of Cycle 2. In patients achieving a VGPR or better, ALP increased more than 15 units per liter at Cycle 2 Day 1 over baseline. An ALP increase over the same period of time was seen in 26%, 13% and 11% of patients achieving PR, MR, and SD, respectively. This retrospective analysis of patients with relapsed or refractory myeloma treated with single-agent carfilzomib indicates that early elevation in ALP is associated with subsequent myeloma response.
泛素-蛋白酶体通路通过成骨细胞分化调节骨形成。我们分析了卡非佐米治疗期间碱性磷酸酶 (ALP) 的变化。分析了 38 例复发/难治性多发性骨髓瘤患者参加的 PX-171-003 研究和 29 例患者参加的 PX-171-004 研究的数据。所有患者均接受 20mg/m(2)卡非佐米，于第 1、2、8、9、15 和 16 天，每 28 天一个周期。有 67 例患者可评估 ALP 数据。在 PX-171-003 中，客观缓解率（>部分缓解）为 18%，临床获益反应（>非常好的部分缓解）为 26%，而在 PX-171-004 中，总缓解率为 35.5%，硼替佐米初治患者为 57%。第 2 周期第 1 和第 8 天，与所有其他患者相比，达到≥VGPR 的患者的 ALP 自基线增加具有统计学差异（P=0.0049 和 P=0.006）。在达到 VGPR 或更好缓解的患者中，第 2 周期第 1 天的 ALP 较基线增加超过 15 单位/升。达到 PR、MR 和 SD 的患者在同一时间段内，分别有 26%、13%和 11%的患者出现 ALP 升高。这项对接受单药卡非佐米治疗的复发或难治性骨髓瘤患者的回顾性分析表明，早期 ALP 升高与随后的骨髓瘤反应相关。
