Hematology Department, Catalan Institute of Oncology, Germans Trias i Pujol Hospital and Josep Carreras Research Institute, Badalona, Spain.
Hematology Department, Catalan Institute of Oncology, Duran i Reynals Hospital, L'Hospitalet, Spain.
Eur J Haematol. 2021 Aug;107(2):246-254. doi: 10.1111/ejh.13643. Epub 2021 May 26.
Bortezomib-related peripheral neuropathy (PN) affects a relevant proportion of multiple myeloma (MM) patients treated with melphalan, prednisone, and bortezomib (VMP). Empirical dose modifications have attempted to reduce toxicity without compromising efficacy.
We retrospectively evaluated the dose-response and dose-toxicity relationships in 114 unselected untreated MM patients intended for treatment with VMP with subcutaneous bortezomib.
Sixty-two patients (54%) completed the 9 scheduled cycles. Median treatment duration was 48 weeks (range 1-57), cumulative bortezomib dose was 41.8 mg/m (2.6-67.6) and median dose intensity was 1.0 mg/m /wk (0.2-2.6). Median progression-free survival (PFS) and overall survival (OS) for the full cohort were 86 weeks (95%CI 77-104) and 209 weeks (95% CI 157-259) respectively. Patients who progressed <60 days after discontinuing bortezomib had received a significantly inferior mean cumulative dose, 34.6 mg/m than the remaining individuals, 45.5 (P = .023). PFS was significantly improved for patients achieving a very good partial response (VGPR) or better (P = .00007). Additional variables with a prognostic impact on PFS on univariate analysis included completion of the 9 scheduled cycles (P = .00002), patients with at least 50 weeks of treatment (P = .02) and patients receiving a cumulative dose of at least 49 mg/m (P = .05). Achievement of a VGPR (HR 0.23; 95%CI 0.12-0.46; P = .00002) and a cumulative dose of 49 mg/m (HR 0.46, 95%CI 0.27-0.78; P = .003) were statistically independent prognostic factors for PFS. Toxicity-related treatment dose reductions occurred in 75 individuals (66%). PN was observed in 50 individuals (44.6%), grade 3 in 9 (8%). The only prognostic factor for emergence of PN in multivariate analysis was the presence of baseline PN.
Biweekly full-dose treatment in the first cycles has a major impact in depth of response. Depth of response, cumulative bortezomib dose, and treatment duration had an impact in prolongation of PFS.
硼替佐米相关周围神经病变（PN）影响了相当比例的接受马法兰、泼尼松和硼替佐米（VMP）治疗的多发性骨髓瘤（MM）患者。经验性剂量调整试图降低毒性而不影响疗效。
我们回顾性评估了 114 例未经选择的新诊断 MM 患者接受皮下硼替佐米 VMP 治疗的剂量反应和剂量毒性关系。
62 例患者（54%）完成了 9 个预定周期。中位治疗持续时间为 48 周（范围 1-57），累积硼替佐米剂量为 41.8mg/m（2.6-67.6），中位剂量强度为 1.0mg/m/周（0.2-2.6）。全队列的中位无进展生存期（PFS）和总生存期（OS）分别为 86 周（95%CI 77-104）和 209 周（95%CI 157-259）。在停止硼替佐米后 60 天内进展的患者接受的累积剂量明显低于其余患者，为 34.6mg/m，而其余患者为 45.5mg/m（P=0.023）。对于达到非常好的部分缓解（VGPR）或更好缓解的患者，PFS 显著改善（P=0.00007）。单变量分析中对 PFS 有预后影响的其他变量包括完成 9 个预定周期（P=0.00002）、至少接受 50 周治疗的患者（P=0.02）和接受至少 49mg/m 累积剂量的患者（P=0.05）。达到 VGPR（HR 0.23；95%CI 0.12-0.46；P=0.00002）和 49mg/m 累积剂量（HR 0.46，95%CI 0.27-0.78；P=0.003）是 PFS 的统计学独立预后因素。75 例患者（66%）发生与毒性相关的治疗剂量减少。50 例患者（44.6%）出现周围神经病变，其中 9 例（8%）为 3 级。多变量分析中周围神经病变发生的唯一预后因素是基线周围神经病变的存在。
在第一个周期中每周两次全剂量治疗对反应深度有重大影响。反应深度、累积硼替佐米剂量和治疗持续时间对 PFS 的延长有影响。
