背景:多发性骨髓瘤(MM)是一种常见的血液系统恶性肿瘤,起源于浆细胞的恶性克隆。孤立性浆细胞瘤,糖尿病史,血小板计数被认为是MM的预后因素。但是一些患者仍然与更糟糕的结果相关,没有任何预后预测因子。本研究旨在观察第一和第四周期化疗后单克隆蛋白(M蛋白)的降低率,这被认为是新诊断的MM患者标准风险组的无进展生存期(PFS)的新预后因素。
目的:探讨第1、第4周期化疗后M蛋白的降低率作为一个有用的预后因子。
方法:收集丽水市中心医院2010-2019年首次诊断为MM的316例患者。所有患者均根据国家综合癌症网络(NCCN)2020进行诊断。V1诊断标准。风险评估是根据Mayo巨球蛋白血症分层和风险适应治疗指南进行的。诊断后,对164例患者进行了评估,并接受了4至8个疗程的连续诱导化疗。诱导治疗后无反应的患者在NCCN2020后给予额外的治疗。V1标准。收集患者的以下基线数据:性别,诊断时的年龄,Durie-三文鱼舞台,谷氨酸-丙酮酸转氨酶,谷氨酸-草酰乙酸转氨酶,分解代谢物激活蛋白,白蛋白/球蛋白比,乳酸脱氢酶,易位(t)(6;14),t(11;14),维持方案,总胆固醇(TC),甘油三酯,和磷。通过单因素分析评估从第一到第四的每个化疗周期后的所有基线数据和M蛋白的减少率。然后通过多因素分析评估影响总生存期和PFS的因素。我们发现第一周期(C1)减少率和第四周期(C4)减少率作为PFS的预测因子。然后,比较M蛋白C1降低率≥25%vs<25%和≥50%vs<50%的患者的PFS,在C4降低率≥25%和<25%的患者之间,≥50%vs<50%,≥75%vs<75%。
结果:多变量分析显示年龄[风险比(HR):1.059,95%置信区间(95CI):1.033-1.085,P≤0.001],国际分期系统阶段(HR:2.136,95CI:1.500-3.041,P≤0.001),自动着陆(HR:0.201,95CI:0.069-0.583,P=0.019),TC(HR:0.689,95CI:0.533-0.891,P=0.019),C1降低率(HR:0474,95CI:0.293-0.767,P=0.019),和C4降低率(HR:0.254,95CI:0.139-0.463,P=0.019)作为PFS的预测因子。Kaplan-Meier生存分析和对数秩检验显示,第一个周期(≥50%)和第四个周期(≥75%)化疗后,M蛋白的降低率较高,与较低的PFS有关。
结论:首次和第四次化疗后M蛋白降低率较高,可作为标准风险组MM患者初始诊断期间PFS的有利预后因素。
BACKGROUND: Multiple myeloma (MM) is a common hematologic malignancy that originates from a malignant clone of plasma cells. Solitary plasmacytoma, history of diabetes, and platelet count are considered as prognostic factors for MM. But some patients are still associated with much worse outcomes without any prognostic predictors. This study aimed to observe the reduction rate of monoclonal protein (M protein) after the first and fourth chemotherapy cycles, which is considered as a new prognostic factor for progression-free survival (PFS) in standard-risk group of newly diagnosed MM patients.
OBJECTIVE: To investigate the reduction rate of M protein after first and fourth cycle chemotherapy as a useful prognostic factor.
METHODS: A total of 316 patients diagnosed with MM for the first time between 2010 and 2019 at the Lishui Municipal Central Hospital were included. All patients were diagnosed according to the National Comprehensive Cancer Network (NCCN) 2020.V1 diagnostic criteria. The risk assessment was performed by the Mayo Stratification for Macroglobulinemia and Risk-Adapted Therapy guidelines. After diagnosis, 164 patients were evaluated and underwent treatment with four to eight courses of continuous induction chemotherapy. The patients with no response after induction treatment were administered additional therapy following the NCCN 2020.V1 criteria. The following baseline data from the patients were collected: Gender, age at diagnosis, Durie-Salmon stage, glutamic-pyruvic transaminase, glutamic-oxaloacetic transaminase, catabolite activator protein, albumin/globulin ratio, lactate dehydrogenase, translocation (t)(6;14), t(11;14), maintenance regimen, total cholesterol (TC), triglyceride, and phosphorous. All baseline data and the reduction rate of M protein after each chemotherapy cycle from the first to fourth were assessed by univariate analysis. The factors influencing the overall survival and PFS were then assessed by multivariate analysis. We found the first cycle (C1) reduction rate and the fourth cycle (C4) reduction rate as predictors of PFS. Then, PFS was compared between patients with a C1 reduction rate of M protein of ≥ 25% vs < 25% and ≥ 50% vs < 50%, and between patients with a C4 reduction rate of ≥ 25% vs < 25%, ≥ 50% vs < 50%, and ≥ 75% vs < 75%.
RESULTS: Multivariate analysis revealed age [hazard ratio (HR): 1.059, 95% confidence interval (95%CI): 1.033-1.085, P ≤ 0.001], International Staging System stage (HR: 2.136, 95%CI: 1.500-3.041, P ≤ 0.001), autotransplantion (HR: 0.201, 95%CI: 0.069-0.583, P = 0.019), TC (HR: 0.689, 95%CI: 0.533-0.891, P = 0.019), C1 reduction rate (HR: 0474, 95%CI: 0.293-0.767, P = 0.019), and C4 reduction rate (HR: 0.254, 95%CI: 0.139-0.463, P = 0.019) as predictors of PFS. The Kaplan-Meier survival analysis and the log-rank tests revealed that a higher reduction rate of M protein after first cycle (≥ 50%) and fourth cycle (≥ 75%) chemotherapy was associated with a longer PFS than the lower one.
CONCLUSIONS: Higher reduction rates of M protein after the first and fourth chemotherapy cycles can act as advantageous prognostic factors for PFS in standard-risk group of MM patients during initial diagnosis.