Taussig Cancer Center, Cleveland Clinic, Cleveland, OH, USA.
Department of Pharmacy, Cleveland Clinic, Cleveland, OH, USA.
Br J Haematol. 2020 Jun;189(6):1074-1082. doi: 10.1111/bjh.16488. Epub 2020 Feb 28.
Characterisation and prognostic impact of immunoparesis in relapsed multiple myeloma (MM) is lacking in the current literature. We evaluated 258 patients with relapsed MM, diagnosed from 2008 to 2015, to investigate the prognostic impact of deep immunoparesis on post-relapse survival. On qualitative immunoparesis assessment, no, partial and full immunoparesis was present in 9%, 30% and 61% of patients, respectively. Quantitative immunoparesis was assessed by computing the average relative difference (ARD) between polyclonal immunoglobulin(s) and corresponding lower normal limit(s), with greater negative values indicating deeper immunoparesis. The median ARD was -39%, with an optimal cut-off of -50% for overall survival (OS) by recursive partitioning analysis. Deep immunoparesis (ARD ≤-50%) was associated with a higher tumour burden at first relapse compared to none/shallow [ARD >-50%] immunoparesis. The OS (P = 0·007) and progression-free survival (PFS; P < 0·001) differed significantly between the deep and none/shallow immunoparesis groups. Kaplan-Meier estimates for 3-year OS were 36% and 46%, and for 2-year PFS were 17% and 27%, respectively. On multivariable analysis (MVA) for PFS, both qualitative and quantitative immunoparesis retained negative prognostic impact independently. However, only quantitative immunoparesis was independently prognostic for OS on MVA. Depth of immunoparesis in relapsed MM is an important prognostic factor for post-relapse survival in the era of novel agents and continuous therapy.
在当前的文献中，复发多发性骨髓瘤（MM）的免疫缺陷特征及其对预后的影响尚不清楚。我们评估了 258 例 2008 年至 2015 年间诊断为复发 MM 的患者，以研究深度免疫缺陷对复发后生存的预后影响。在定性免疫缺陷评估中，分别有 9%、30%和 61%的患者存在无、部分和完全免疫缺陷。通过计算多克隆免疫球蛋白（s）和相应的正常下限（s）之间的平均相对差异（ARD）来评估定量免疫缺陷，负值越大表示免疫缺陷越深。中位数 ARD 为-39%，通过递归分区分析，OS 的最佳截断值为-50%。与无/轻度免疫缺陷（ARD＞-50%）相比，深度免疫缺陷（ARD≤-50%）患者在首次复发时的肿瘤负荷更高。OS（P=0.007）和无进展生存期（PFS；P＜0.001）在深度和无/轻度免疫缺陷组之间差异显著。深度和无/轻度免疫缺陷组 3 年 OS 的 Kaplan-Meier 估计值分别为 36%和 46%，2 年 PFS 分别为 17%和 27%。在 PFS 的多变量分析（MVA）中，定性和定量免疫缺陷均独立保留了负预后影响。然而，仅定量免疫缺陷在 MVA 中对 OS 具有独立的预后意义。在新型药物和持续治疗时代，复发 MM 中的免疫缺陷深度是复发后生存的一个重要预后因素。
