Department of Hematology, National Hospital Organization Okayama Medical Center, 1711-1 Tamasu, Kita-ku, Okayama, 701-1192, Japan.
Department of Hematology, National Hospital Organization Shibukawa Medical Center, 383 Shirai, Shibukawa, Gunma, 377-0280, Japan.
Int J Clin Oncol. 2019 Aug;24(8):966-975. doi: 10.1007/s10147-019-01436-8. Epub 2019 Apr 1.
The Japan Study Group for Cell Therapy and Transplantation (JSCT) organized a phase II study to evaluate the efficacy and safety of a treatment protocol (JSCT-MM12) for multiple myeloma (MM) patients who were previously untreated and transplantation-eligible. Since bortezomib-based therapy is known to be effective for MM, the protocol is intensified more than the previous protocol (JSCT-MM10) and comprised the subsequent treatments: bortezomib + cyclophosphamide + dexamethasone (VCD) induction; bortezomib + high-dose-melphalan (B-HDM) conditioning with autologous stem cell transplantation (ASCT); bortezomib + thalidomide + dexamethasone (VTD) consolidation; and lenalidomide (LEN) maintenance.
Sixty-four symptomatic patients aged between 20 and 65 years were enrolled for treatment and received three cycles of VCD, followed by cyclophosphamide administration for autologous stem cell harvest and B-HDM/ASCT, and subsequently two cycles of VTD, after that LEN for 1 year.
Complete response (CR)/stringent CR (sCR) rates for induction, ASCT, consolidation, and maintenance therapies were 20, 39, 52, and 56%, respectively. The grade 3/4 toxicities (≥ 10%) with VCD treatment included neutropenia (27%), anemia (19%), and thrombocytopenia (11%). There was no treatment-related mortality. After median follow-up of 41 months, estimated 3-year progression-free survival (PFS) and overall survival (OS) rates were 64% and 88%, respectively. The high-risk group revealed lower CR/sCR, PFS, and OS than the standard-risk group.
The study revealed that the treatment protocol consisting of VCD induction, B-HDM/ASCT followed by VTD consolidation, and LEN maintenance could produce highly beneficial responses and favorable tolerability in newly diagnosed MM. However, future study is required for improving treatment in the high-risk group.
日本细胞治疗与移植研究小组（JSCT）组织了一项 II 期研究，旨在评估针对既往未经治疗且适合移植的多发性骨髓瘤（MM）患者的治疗方案（JSCT-MM12）的疗效和安全性。由于硼替佐米为基础的治疗对 MM 有效，因此该方案比之前的方案（JSCT-MM10）更为强化，包括以下后续治疗：硼替佐米+环磷酰胺+地塞米松（VCD）诱导；硼替佐米+高剂量马法兰（B-HDM）预处理联合自体干细胞移植（ASCT）；硼替佐米+沙利度胺+地塞米松（VTD）巩固；以及来那度胺（LEN）维持。
64 名年龄在 20 至 65 岁之间的有症状患者接受了治疗，并接受了三个周期的 VCD 治疗，随后进行环磷酰胺给药以采集自体干细胞，并进行 B-HDM/ASCT，随后进行两个周期的 VTD 治疗，之后接受 LEN 治疗 1 年。
诱导、ASCT、巩固和维持治疗的完全缓解（CR）/严格 CR（sCR）率分别为 20%、39%、52%和 56%。VCD 治疗的 3/4 级毒性（≥10%）包括中性粒细胞减少症（27%）、贫血（19%）和血小板减少症（11%）。无治疗相关死亡。中位随访 41 个月后，估计 3 年无进展生存率（PFS）和总生存率（OS）分别为 64%和 88%。高危组的 CR/sCR、PFS 和 OS 均低于标准风险组。
该研究表明，由 VCD 诱导、B-HDM/ASCT 后继以 VTD 巩固和 LEN 维持组成的治疗方案可在新诊断的 MM 患者中产生高度有益的反应和良好的耐受性。然而，需要进一步的研究来改善高危组的治疗。
