El-Cheikh Jean, Stoppa Anne-Marie, Bouabdallah Réda, de Lavallade Hugues, Coso Diane, de Collela Jean-Marc Schiano, Auran-Schleinitz Thérèse, Gastaut Jean-Albert, Blaise Didier, Mohty Mohamad
Unité de Transplantation et de Thérapie Cellulaire, Institut Paoli-Calmettes, Marseille, France.
Clin Lymphoma Myeloma. 2008 Jun;8(3):146-52. doi: 10.3816/CLM.2008.n.017.
Bortezomib is a first-in-class proteasome inhibitor with remarkable antitumor activity that is approved for the treatment of patients with multiple myeloma. Peripheral neuropathy (PN) is a frequent adverse event reported with bortezomib use.
The aim of this retrospective, single-center study was to determine the characteristics of bortezomib-associated PN in 100 patients with advanced myeloma. Peripheral neuropathy was evaluated by investigator's assessment.
With a median follow-up of 8 months (range, 0.1-32 months) from bortezomib initiation, bortezomib-associated PN was observed in 38 patients (38%; 95% CI, 28%-47%), with grade 3 and 4 PN occurring in 5 patients and 1 patient, respectively. Median time to onset of bortezomib-associated PN was 53 days (range, 11-182 days). Of the 38 patients with bortezomib-associated PN, resolution or improvement occurred in 20 patients (53%) at a median of 3 months (range, 1-8 months). In multivariate analysis, the total number of cycles of bortezomib (< 4 cycles or > 4 cycles; P = .03; odds ratio [OR], 2.6; 95% CI, 1.1-6.1) and a previous history of thalidomide therapy (P = .02; OR, 3.9; 95% CI, 1.2-12.6) were significantly associated with an increased incidence of bortezomib-associated PN.
We conclude that, though relatively frequent, bortezomib-associated PN is reversible in a majority of patients. However, bortezomib-associated PN seems to be dependent on previous therapy with thalidomide, suggesting that bortezomib followed by thalidomide could be an optimal sequence of administration of these drugs in the salvage setting.
硼替佐米是首个蛋白酶体抑制剂,具有显著的抗肿瘤活性,已被批准用于治疗多发性骨髓瘤患者。周围神经病变(PN)是使用硼替佐米时常见的不良事件。
这项回顾性单中心研究的目的是确定100例晚期骨髓瘤患者中硼替佐米相关PN的特征。周围神经病变由研究者评估。
从开始使用硼替佐米起,中位随访8个月(范围0.1 - 32个月),38例患者(38%;95%置信区间,28% - 47%)出现硼替佐米相关PN,3级和4级PN分别发生在5例和1例患者中。硼替佐米相关PN的中位发病时间为53天(范围11 - 182天)。在38例硼替佐米相关PN患者中,20例(53%)在中位3个月(范围1 - 8个月)时病情缓解或改善。多因素分析显示,硼替佐米的总疗程数(<4个疗程或>4个疗程;P = 0.03;比值比[OR],2.6;95%置信区间,1.1 - 6.1)和既往沙利度胺治疗史(P = 0.02;OR,3.9;95%置信区间,1.2 - 12.6)与硼替佐米相关PN的发生率增加显著相关。
我们得出结论,尽管硼替佐米相关PN相对常见,但在大多数患者中是可逆的。然而,硼替佐米相关PN似乎依赖于既往沙利度胺治疗,这表明在挽救治疗中,硼替佐米后使用沙利度胺可能是这些药物的最佳给药顺序。