Department of Cardiology, Hillingdon Hospital, Pield Heath Road, Uxbridge, Middlesex, UB8 3NN, UK.
QJM. 2011 Nov;104(11):957-70. doi: 10.1093/qjmed/hcr105. Epub 2011 Jul 13.
Bortezomib is approved for the treatment of multiple myeloma and a role has been suggested in the treatment of systemic AL amyloidosis (AL).
In this phase 1 dose-escalation portion of the first prospective study of single-agent bortezomib in AL, 31 patients with relapsed disease, including 14 (45%) with cardiac involvement, received bortezomib in seven dose cohorts on once-weekly (0.7, 1.0, 1.3, 1.6 mg/m(2)) and twice-weekly (0.7, 1.0, 1.3 mg/m(2)) schedules. Electrocardiographic, Holter and echocardiographic studies were evaluated in all patients to determine safety and response.
During therapy (median treatment period 210 days), no patient developed significant ventricular or supraventricular rhythm disturbance on 24-h Holter monitoring; however, no patient satisfied study criteria for cardiac response using echocardiographic assessment or New York Heart Association classification. Seven patients (23%) had a ≥ 10% fall in left ventricular ejection fraction, but only one met criteria for cardiac deterioration. The predominant cardiac adverse events were peripheral edema (23%), orthostatic hypotension (13%) and hypotension (10%). Two patients developed grade 3 congestive heart failure, which resolved following treatment interruption. In this Phase 1 portion, the maximum tolerated dose of bortezomib on either schedule was not reached. Hematologic responses occurred in 14 patients (45%), including seven (23%) complete responses. In non-responders mean left ventricular wall thickness increased during the course of treatment.
AL is frequently rapidly progressive; in these patients who had relapsed or progressed following previous conventional therapies, these results suggest that bortezomib may slow the progression of cardiac amyloid with limited toxicity.
硼替佐米已被批准用于治疗多发性骨髓瘤，并被认为在治疗系统性 AL 淀粉样变性（AL）中具有一定作用。
在这项针对 AL 患者进行的单次使用硼替佐米的首个前瞻性研究的 1 期剂量递增部分，31 例复发性疾病患者，包括 14 例（45%）有心脏受累，每周接受 7 个剂量组的硼替佐米治疗，方案为每周一次（0.7、1.0、1.3、1.6mg/m2）和每周两次（0.7、1.0、1.3mg/m2）。所有患者均进行心电图、动态心电图和超声心动图检查，以评估安全性和反应。
在治疗期间（中位治疗期 210 天），没有患者在 24 小时动态心电图监测中出现明显的室性或室上性节律紊乱；然而，没有患者符合超声心动图评估或纽约心脏协会分类的心脏反应研究标准。7 例（23%）患者左心室射血分数下降≥10%，但只有 1 例符合心脏恶化的标准。主要的心脏不良事件是外周水肿（23%）、体位性低血压（13%）和低血压（10%）。2 例患者出现 3 级充血性心力衰竭，中断治疗后得到缓解。在这个 1 期部分，两种方案均未达到硼替佐米的最大耐受剂量。14 例患者（45%）出现血液学反应，包括 7 例（23%）完全反应。在无反应者中，左心室壁厚度在治疗过程中增加。
AL 通常进展迅速；在这些患者中，在先前的常规治疗后复发或进展，这些结果表明硼替佐米可能会减缓心脏淀粉样变的进展，同时毒性有限。
