Reece Donna E, Hegenbart Ute, Sanchorawala Vaishali, Merlini Giampaolo, Palladini Giovanni, Bladé Joan, Fermand Jean-Paul, Hassoun Hani, Heffner Leonard, Kukreti Vishal, Vescio Robert A, Pei Lixia, Enny Christopher, Esseltine Dixie-Lee, van de Velde Helgi, Cakana Andrew, Comenzo Raymond L
Princess Margaret Cancer Center, Toronto, ON, Canada;
Amyloidosis Center, University of Heidelberg, Heidelberg, Germany;
Blood. 2014 Oct 16;124(16):2498-506. doi: 10.1182/blood-2014-04-568329. Epub 2014 Sep 8.
CAN2007 was a phase 1/2 study of once- and twice-weekly single-agent bortezomib in relapsed primary systemic amyloid light chain amyloidosis (AL) amyloidosis. Seventy patients were treated, including 18 and 34 patients at the maximum planned doses on the once- and twice-weekly schedules. This prespecified final analysis provides mature response and long-term outcomes data after 3-year additional follow-up since the last report. In the once-weekly 1.6 mg/m(2) and twice-weekly 1.3 mg/m(2) bortezomib groups, final hematologic response rates were 68.8% and 66.7%; 80% of patients in each group sustained their response for ≥1 year. One-year progression-free rates were 72.2% and 76.8%. Median overall survival (OS) was 62.1 months and not reached; 4-year OS rates were 75.0% and 63.0%. Low baseline difference in κ/λ free light-chain level was associated with higher hematologic complete response rates and longer OS. At data cutoff, 40 (57%) patients had received subsequent therapy, including 19 (27%) retreated with bortezomib, 11 (58%) of whom achieved complete or partial hematologic responses. Four patients received prolonged bortezomib for between 3.5 and 5.6 years, with no new safety concerns, highlighting the feasibility of long-term therapy. Single-agent bortezomib produced durable hematologic responses and promising long-term OS in relapsed AL amyloidosis. This trial was registered at www.clinicaltrials.gov as #NCT00298766.
CAN2007是一项1/2期研究，旨在评估每周一次和每周两次单药硼替佐米治疗复发的原发性系统性轻链型淀粉样变性（AL）。共治疗了70例患者，其中18例和34例分别接受了每周一次和每周两次给药方案的最大计划剂量治疗。本次预先设定的最终分析提供了自上次报告以来3年额外随访后的成熟缓解和长期结局数据。在每周一次1.6mg/m²和每周两次1.3mg/m²硼替佐米组中，最终血液学缓解率分别为68.8%和66.7%；每组80%的患者缓解持续时间≥1年。一年无进展率分别为72.2%和76.8%。中位总生存期（OS）为62.1个月且未达到；4年OS率分别为75.0%和63.0%。κ/λ游离轻链水平的低基线差异与更高的血液学完全缓解率和更长的OS相关。在数据截止时，40例（57%）患者接受了后续治疗，其中19例（27%）接受硼替佐米再治疗，11例（58%）获得了完全或部分血液学缓解。4例患者接受了3.5至5.6年的延长硼替佐米治疗，未出现新的安全问题，突出了长期治疗的可行性。单药硼替佐米在复发的AL淀粉样变性中产生了持久的血液学缓解和有前景的长期OS。该试验已在www.clinicaltrials.gov上注册，编号为#NCT00298766。
