Princess Margaret Hospital, Toronto, ON, Canada.
Blood. 2011 Jul 28;118(4):865-73. doi: 10.1182/blood-2011-02-334227. Epub 2011 May 11.
This first prospective phase 2 study of single-agent bortezomib in relapsed primary systemic AL amyloidosis evaluated the recommended (maximum planned) doses identified in phase 1 testing (1.6 mg/m² once weekly [days 1, 8, 15, and 22; 35-day cycles]; 1.3 mg/m² twice weekly [days 1, 4, 8, and 11; 21-day cycles]). Among all 70 patients enrolled in the study, 44% had ≥ 3 organs involved, including 73% and 56% with renal and cardiac involvement. In the 1.6 mg/m² once-weekly and 1.3 mg/m² twice-weekly groups, the hematologic response rate was 68.8% and 66.7% (37.5% and 24.2% complete responses, respectively); median time to first/best response was 2.1/3.2 and 0.7/1.2 months, and 78.8% and 75.5% had response durations of ≥ 1 year, respectively. One-year hematologic progression-free rates were 72.2% and 74.6%, and 1-year survival rates were 93.8% and 84.0%, respectively. Outcomes appeared similar in patients with cardiac involvement. Among all 70 patients, organ responses included 29% renal and 13% cardiac responses. Rates of grade ≥ 3 toxicities (79% vs 50%) and discontinuations/dose reductions (38%/53% vs 28%/22%) resulting from toxicities appeared higher with 1.3 mg/m² twice-weekly versus 1.6 mg/m² once-weekly dosing. Both bortezomib dose schedules represent active, well-tolerated regimens in relapsed AL amyloidosis. This study was registered at www.clinicaltrials.gov as #NCT00298766.
这是一项针对复发性原发性系统性淀粉样变的硼替佐米单药治疗的首次前瞻性 2 期研究，评估了 1 期试验中确定的推荐（最大计划）剂量（每周一次 1.6mg/m²[第 1、8、15 和 22 天；35 天周期]；每周两次 1.3mg/m²[第 1、4、8 和 11 天；21 天周期]）。在该研究纳入的所有 70 名患者中，44%有≥3 个器官受累，包括 73%和 56%有肾脏和心脏受累。在每周一次 1.6mg/m²和每周两次 1.3mg/m²组中，血液学缓解率分别为 68.8%和 66.7%（分别为 37.5%和 24.2%完全缓解）；首次/最佳缓解的中位时间分别为 2.1/3.2 和 0.7/1.2 个月，78.8%和 75.5%的缓解持续时间≥1 年。1 年血液学无进展生存率分别为 72.2%和 74.6%，1 年生存率分别为 93.8%和 84.0%。在有心脏受累的患者中，结局似乎相似。在所有 70 名患者中，器官缓解包括 29%的肾脏缓解和 13%的心脏缓解。≥3 级毒性发生率（79%比 50%）和因毒性而停药/剂量减少（38%/53%比 28%/22%）似乎在每周两次 1.3mg/m²与每周一次 1.6mg/m²组中更高。两种硼替佐米剂量方案在复发性 AL 淀粉样变性中均为有效且耐受良好的方案。本研究在 www.clinicaltrials.gov 上注册为 #NCT00298766。
