Bühler Selina, Akhoundova Dilara, Jeker Barbara, Legros Myriam, Seipel Katja, Daskalakis Michael, Bacher Ulrike, Pabst Thomas
Department of Medical Oncology, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland.
Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland.
Cancers (Basel). 2023 Jan 9;15(2):430. doi: 10.3390/cancers15020430.
(1) Background: High-dose chemotherapy (HDCT) followed by autologous stem cell transplantation (ASCT) is the standard consolidation strategy for patients with newly diagnosed multiple myeloma (MM) and for a subset of patients with relapsed/refractory disease. For stem cell mobilization, G-CSF alone or in combination with chemotherapy mobilizing agents and/or plerixafor are commonly used. Ixazomib is an oral proteasome inhibitor with less neurotoxic potential, which previously showed the ability to mobilize stem cells in preclinical studies. (2) Methods: Prospective single-center phase 1 study assessing the efficacy and safety of stem cell mobilization with ixazomib and G-CSF in patients with newly diagnosed or relapsed/refractory MM undergoing HDCT and ASCT. Primary endpoint was percentage of patients achieving a yield of at least 6.0 × 10/kg CD34+ cells within the first apheresis. G-CSF (filgrastim) 10 μg/kg/day was administered subcutaneously (s.c.) from day 1 to day 5 (planned apheresis) and ixazomib 4 mg orally at day 4. Plerixafor 24 mg s.c. was administered if the stem cell mobilization with ixazomib and G-CSF was not sufficient. (3) Results: 19 patients were treated within the study between 06/2020 and 02/2021. The primary endpoint was reached in 17 (89%) patients, with a median of 7.1 × 10/kg CD34+ cells collected within the first apheresis, comparable to previously published results, and only 2 (11%) patients required a second apheresis. Median number of circulating CD34+ cells was 14.0 × 10/L (2.0-95.2) before the administration of ixazomib, and 33.0 × 10/L (4.2-177.0) pre-apheresis. However, 9 (47%) patients required the addition of plerixafor to ensure optimal stem cell collection. (4) Conclusions: The combination of ixazomib and G-CSF showed promising stem cell mobilizing activity in patients with MM prior to HDCT and ASCT. Future larger studies might further investigate the role of ixazomib in stem cell mobilization regimens for MM.
（1）背景：大剂量化疗（HDCT）后进行自体干细胞移植（ASCT）是新诊断的多发性骨髓瘤（MM）患者以及部分复发/难治性疾病患者的标准巩固治疗策略。对于干细胞动员，常用单独使用粒细胞集落刺激因子（G-CSF）或与化疗动员剂和/或普乐沙福联合使用。伊沙佐米是一种口服蛋白酶体抑制剂，神经毒性潜力较小，此前在临床前研究中显示出动员干细胞的能力。（2）方法：一项前瞻性单中心1期研究，评估伊沙佐米和G-CSF对接受HDCT和ASCT的新诊断或复发/难治性MM患者进行干细胞动员的疗效和安全性。主要终点是在首次单采术中获得至少6.0×10⁶/kg CD34⁺细胞的患者百分比。从第1天至第5天（计划单采）皮下注射（s.c.）G-CSF（非格司亭）10μg/kg/天，并在第4天口服伊沙佐米4mg。如果伊沙佐米和G-CSF进行的干细胞动员不足，则皮下注射普乐沙福24mg。（3）结果：2020年6月至2021年2月期间，19例患者在该研究中接受了治疗。17例（89%）患者达到主要终点，首次单采术中收集的CD34⁺细胞中位数为7.1×10⁶/kg，与先前发表的结果相当，只有2例（11%）患者需要进行第二次单采。在给予伊沙佐米之前，循环CD34⁺细胞的中位数为14.0×10⁹/L（2.0 - 95.2），单采术前为33.0×10⁹/L（4.2 - 177.0）。然而，9例（47%）患者需要加用普乐沙福以确保最佳的干细胞采集。（4）结论：伊沙佐米和G-CSF的联合用药在HDCT和ASCT前的MM患者中显示出有前景的干细胞动员活性。未来更大规模的研究可能会进一步探究伊沙佐米在MM干细胞动员方案中的作用。
