Rush University Medical Center, Chicago, IL 60612, USA.
Clin Lymphoma Myeloma Leuk. 2011 Dec;11(6):467-74. doi: 10.1016/j.clml.2011.04.009. Epub 2011 Jun 22.
We conducted a single-institution phase II clinical trial evaluating the safety and efficacy of combination chemoimmunotherapy followed by radioimmunotherapy consolidation and rituximab maintenance as front-line treatment in indolent lymphomas.
We enrolled 20 patients with intermediate- to high-risk follicular lymphoma and 2 patients with marginal zone lymphoma. Treatment consisted of 4-6 cycles of FM (fludarabine 25 mg/m(2) on days 1-3, mitoxantrone 12 mg/m(2) on day 1 of each 28-day cycle). The protocol was amended after enrolling the first 4 patients to include rituximab 375 mg/m(2) on day 1. After 6-8 weeks, responders received (90)Y-ibritumomab tiuxetan (Zevalin) followed by maintenance rituximab (375 mg/m(2) weekly × 4 doses, repeated every 6 months for 2 years).
After R-FM, the overall response rate was 95% with a complete response rate (CR) of 45% (n = 10), a partial response (PR) rate of 50% (n = 11), and stable disease in 1 patient. Nineteen patients received (90)Y-ibritumomab tiuxetan with a 60% conversion rate of PR to CR, resulting in an improved CR of 79% (n = 15) and a PR of 21% (n = 4). Fifteen patients proceeded to rituximab maintenance resulting in 3 patients with PR converting to CR. At median follow-up of 49.6 months, median progression-free survival (PFS) was 47.2 months and median overall survival (OS) was not reached in an intent-to-treat analysis. The most common adverse effects were hematologic, with 2 patients experiencing treatment-related myelodysplastic syndrome (MDS), evolving to acute myelogenous leukemia (AML) in 1 patient.
R-FM with (90)Y-ibritumomab tiuxetan consolidation and rituximab maintenance is well tolerated, improving CR rates and maintaining durable responses in patients with untreated indolent lymphomas.
我们进行了一项单机构的二期临床试验，评估了联合化疗免疫治疗后进行放射性免疫治疗巩固和利妥昔单抗维持治疗作为惰性淋巴瘤一线治疗的安全性和疗效。
我们招募了 20 名中高危滤泡淋巴瘤患者和 2 名边缘区淋巴瘤患者。治疗包括 4-6 个周期的 FM（氟达拉滨 25mg/m2，第 1-3 天；米托蒽醌 12mg/m2，每个 28 天周期的第 1 天）。在招募了前 4 名患者后，方案进行了修改，包括在第 1 天给予利妥昔单抗 375mg/m2。6-8 周后，应答者接受（90）Y-依鲁替尼单抗替伊莫单抗（Zevalin）治疗，随后进行利妥昔单抗维持治疗（375mg/m2，每周 1 次，共 4 剂，每 6 个月重复 2 年）。
R-FM 后，总体缓解率为 95%，完全缓解率（CR）为 45%（n=10），部分缓解率（PR）为 50%（n=11），1 例患者疾病稳定。19 名患者接受（90）Y-依鲁替尼单抗替伊莫单抗治疗，PR 转化率为 60%，CR 率提高至 79%（n=15），PR 率为 21%（n=4）。15 名患者接受利妥昔单抗维持治疗，其中 3 名 PR 患者转为 CR。在中位随访 49.6 个月时，意向治疗分析中，中位无进展生存期（PFS）为 47.2 个月，中位总生存期（OS）未达到。最常见的不良反应是血液学毒性，2 名患者发生治疗相关骨髓增生异常综合征（MDS），1 名患者进展为急性髓系白血病（AML）。
R-FM 联合（90）Y-依鲁替尼单抗替伊莫单抗巩固治疗和利妥昔单抗维持治疗耐受性良好，可提高未经治疗的惰性淋巴瘤患者的 CR 率，并保持持久缓解。
