Ibata Soushi, Sato Tsutomu, Kuroda Hiroyuki, Nagamachi Yasuhiro, Iyama Satoshi, Fujimi Akihito, Kamihara Yusuke, Konuma Yuichi, Yoshida Masahiro, Tatekoshi Ayumi, Hashimoto Akari, Horiguchi Hiroto, Ono Kaoru, Murase Kazuyuki, Takada Kohichi, Miyanishi Koji, Kobune Masayoshi, Hirayama Yasuo, Kato Junji
Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, South-1 West-16, Chuo-ku, Sapporo, Japan.
Gastroenterology and Hematology/Clinical Oncology, Internal Medicine, Steel Memorial Muroran Hospital, Muroran, Japan.
Cancer Chemother Pharmacol. 2016 Nov;78(5):1041-1049. doi: 10.1007/s00280-016-3163-y. Epub 2016 Oct 13.
Consolidation/maintenance therapy induces deep remission in patients with multiple myeloma (MM); however, the most suitable regimen has been under investigation. The combination therapy with bortezomib, lenalidomide and dexamethasone (VRD) is a powerful regimen for relapsed/refractory as well as newly diagnosed MM as an induction therapy. However, severe adverse events (AEs) may become a problem when VRD is introduced without dose reduction as a consolidation/maintenance therapy.
In this single-arm phase II study, we evaluated the efficacy of small-dose VRD regimen (sVRD) in the consolidation/maintenance setting. Sixteen patients who had partial response (PR) or better after any induction therapy were enrolled. Patients received at least six 28-day cycles of subcutaneous bortezomib (1.3 mg/m on days 1 and 15), lenalidomide (10 mg on days 1-21) and dexamethasone (40 mg on days 1, 8, 15 and 22).
The overall response rate and the complete response (CR) rate were 100 and 43.8 %, respectively. In particular, one patient with CR and two patients with very good PR at enrollment achieved stringent CR during 6 courses of sVRD. With a median follow-up time of 29.4 months, the median progression-free survival (PFS) and overall survival (OS) were not reached, while the PFS and OS rates at 2.5 years were 66.6 and 77.3 %, respectively. Univariate analysis demonstrated that disease progression as a reason for discontinuation of sVRD had a negative impact on OS. There were no grade 3 or 4 hematologic or nonhematologic AEs.
Our sVRD regimen as a consolidation/maintenance therapy was highly effective and well tolerable.
巩固/维持治疗可使多发性骨髓瘤（MM）患者实现深度缓解；然而，最合适的治疗方案一直在研究中。硼替佐米、来那度胺和地塞米松联合治疗（VRD）是复发/难治性以及新诊断MM诱导治疗的有效方案。然而，当VRD作为巩固/维持治疗未减量引入时，严重不良事件（AE）可能成为问题。
在这项单臂II期研究中，我们评估了小剂量VRD方案（sVRD）在巩固/维持治疗中的疗效。纳入16例在任何诱导治疗后获得部分缓解（PR）或更好疗效的患者。患者接受至少六个28天周期的皮下注射硼替佐米（第1天和第15天1.3mg/m²）、来那度胺（第1 - 21天10mg）和地塞米松（第1、8、15和22天40mg）。
总缓解率和完全缓解（CR）率分别为100%和43.8%。特别是，1例入组时CR患者和2例非常好的PR患者在6个疗程的sVRD治疗期间实现了严格CR。中位随访时间为29.4个月，中位无进展生存期（PFS）和总生存期（OS）未达到，而2.5年时的PFS和OS率分别为66.6%和77.3%。单因素分析表明，因疾病进展停用sVRD对OS有负面影响。无3级或4级血液学或非血液学AE。
我们的sVRD方案作为巩固/维持治疗具有高度有效性且耐受性良好。
