Mayo Clinic School of Medicine, Rochester, MN, USA.
Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN, USA.
Bone Marrow Transplant. 2019 Apr;54(4):587-594. doi: 10.1038/s41409-018-0302-6. Epub 2018 Aug 16.
Autologous stem cell transplantation (ASCT) remains a mainstay in the treatment of multiple myeloma (MM). While the procedure is generally safe, toxicities associated with high-dose melphalan conditioning are common and significantly affect patient quality of life. Recently, a propylene glycol-free melphalan formulation (PG-free MEL; Evomela®) was approved by the United States Food and Drug Administration as an ASCT-conditioning regimen for MM. PG-free MEL is more soluble and stable than propylene glycol-solubilized melphalan (PG-solubilized MEL; Alkeran®). As such, there is speculation that it could decrease toxicities and increase the efficacy of ASCT. We compared the outcomes of patients conditioned with PG-free MEL (n = 216) to PG-solubilized MEL (n = 200) at our institution. The baseline characteristics were similar between the two groups. After Day +0, there were no differences in terms of hospitalizations, neutropenic fevers, intravenous granisetron requirement, World Health Organization grade ≥ 2 oral/esophageal mucositis, intravenous fluid requirement, or narcotic requirement. However, PG-free MEL patients had a higher incidence of diarrhea, which was mostly C. difficile-negative (82% vs. 71%, P = 0.015*). Day + 100 hematologic responses and progression-free survival after ASCT were comparable. In summary, we demonstrate that switching to PG-free MEL did not significantly reduce short-term complications of ASCT or improve outcomes in MM.
自体干细胞移植 (ASCT) 仍然是多发性骨髓瘤 (MM) 治疗的主要方法。虽然该程序通常是安全的,但与大剂量马法兰预处理相关的毒性是常见的,并且会严重影响患者的生活质量。最近,一种无丙二醇马法兰制剂 (PG-free MEL; Evomela®) 被美国食品和药物管理局批准作为 MM 的 ASCT 预处理方案。PG-free MEL 比丙二醇溶解的马法兰 (PG-solubilized MEL; Alkeran®) 更具溶解性和稳定性。因此,有人推测它可以降低毒性并提高 ASCT 的疗效。我们比较了我们机构中使用 PG-free MEL (n=216) 和 PG-solubilized MEL (n=200) 预处理的患者的结局。两组的基线特征相似。在 Day+0 后,住院、中性粒细胞减少性发热、静脉注射格拉司琼需求、世界卫生组织 (WHO) 分级≥2 级口腔/食管粘膜炎、静脉输液需求或阿片类药物需求方面没有差异。然而,PG-free MEL 患者腹泻的发生率更高,其中大多数为艰难梭菌阴性 (82% vs. 71%,P=0.015*)。ASCT 后第 100 天的血液学反应和无进展生存期相似。总之,我们证明转换为 PG-free MEL 并没有显著降低 ASCT 的短期并发症或改善 MM 的结果。