硼替佐米和利妥昔单抗维持联合治疗巩固自体造血干细胞移植后套细胞淋巴瘤患者的多中心 II 期试验。
Multi-center phase II trial of bortezomib and rituximab maintenance combination therapy in patients with mantle cell lymphoma after consolidative autologous stem cell transplantation.
机构信息
Department of Hematology/Hematopoietic Cell Transplantation, City of Hope National Medical Center, 1500 E Duarte Road, Duarte, CA, 91010, USA.
Department of Information Sciences, City of Hope National Medical Center, Duarte, CA, USA.
出版信息
J Hematol Oncol. 2018 Jun 28;11(1):87. doi: 10.1186/s13045-018-0631-3.
BACKGROUND
Mantle cell lymphoma (MCL) is an aggressive and incurable lymphoma. Standard of care for younger patients with MCL is induction chemotherapy followed by autologous stem cell transplantation (auto-HCT). Rituximab maintenance after auto-HCT has been shown to improve progression-free survival (PFS) and overall survival (OS) in MCL. Bortezomib maintenance therapy has also been shown to be tolerable and feasible in this setting. However, the combination of bortezomib and rituximab as maintenance therapy post-auto-HCT has not been studied.
METHODS
We conducted a multicenter, phase II trial of bortezomib given in combination with rituximab as maintenance in MCL patients after consolidative auto-HCT. Enrolled patients (n = 23) received bortezomib 1.3 mg/m subcutaneously weekly for 4 weeks every 3 months (up to 24 months) and rituximab 375 mg/m intravenously weekly for 4 weeks every 6 months (up to 24 months) for a total duration of 2 years. The primary study endpoint was disease-free survival (DFS).
RESULTS
With a median follow-up of 35.9 months, the 2-year DFS probability was 90.2% (95% CI 66-97), and 2-year OS was 94.7% (95% CI 68-99). The most frequent grade 3/4 toxic events were neutropenia (in 74% of patients) and lymphopenia (in 35%). The incidence of peripheral neuropathy was 48% for grade 1, 9% for grade 2, and 0% for grade 3/4. We also examined the role of quantitative cyclin D1 (CCND1) mRNA in monitoring minimal residual disease.
CONCLUSION
Combined bortezomib and rituximab as maintenance therapy in MCL patients following auto-HCT is an active and well-tolerated regimen.
TRIAL REGISTRATION
ClinicalTrials.gov NCT01267812 , registered Dec 29, 2010.
背景
套细胞淋巴瘤（MCL）是一种侵袭性和无法治愈的淋巴瘤。对于年轻的 MCL 患者，标准治疗方法是诱导化疗后自体造血干细胞移植（auto-HCT）。在 auto-HCT 后进行利妥昔单抗维持治疗已被证明可以改善 MCL 的无进展生存期（PFS）和总生存期（OS）。硼替佐米维持治疗在这种情况下也被证明是可以耐受和可行的。然而，在 auto-HCT 后，硼替佐米和利妥昔单抗联合作为维持治疗尚未进行研究。
方法
我们进行了一项多中心、II 期研究，在 MCL 患者巩固性 auto-HCT 后，使用硼替佐米联合利妥昔单抗进行维持治疗。入组患者（n=23）接受皮下注射硼替佐米 1.3mg/m，每周 1 次，共 4 周，每 3 个月 1 次（最多 24 个月），静脉注射利妥昔单抗 375mg/m，每周 1 次，共 4 周，每 6 个月 1 次（最多 24 个月），总疗程为 2 年。主要研究终点为无疾病生存（DFS）。
结果
中位随访 35.9 个月，2 年 DFS 率为 90.2%（95%CI 66-97），2 年 OS 率为 94.7%（95%CI 68-99）。最常见的 3/4 级毒性事件为中性粒细胞减少（74%的患者）和淋巴细胞减少（35%）。周围神经病变的发生率为 1 级 48%，2 级 9%，3/4 级 0%。我们还研究了定量细胞周期蛋白 D1（CCND1）mRNA 在监测微小残留病中的作用。
结论
在 auto-HCT 后，MCL 患者联合使用硼替佐米和利妥昔单抗作为维持治疗是一种有效且耐受性良好的方案。
试验注册
ClinicalTrials.gov NCT01267812，于 2010 年 12 月 29 日注册。
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