Department of Hematology, Insitute of Hematology, West China Hospital, Sichuan University, Chengdu, China.
Department of Hematology, Clincal Medical College & Affiliated Hospital of Chengdu University, Chengdu, China.
Cancer Med. 2024 Sep;13(17):e70193. doi: 10.1002/cam4.70193.
Chromosomal 1q gains and amplifications (+1q21) are frequently observed in patients with newly diagnosed multiple myeloma (NDMM). However, the interpretation of the high-risk (HR) prognostic implications stemming from 1q21 abnormalities remain challenging to implement effectively.
In a comprehensive analysis of 367 consecutive patients with symptomatic MM, we assessed the prognostic significance of +1q21 using FISH with a threshold of 7.4%. The patient cohort was randomly divided into a training set (66.5%, n = 244) and a validation set (33.5%, n = 133). A multivariate Cox regression analysis was conducted to identify significant prognostic factors associated with PFS. Weight scores were assigned to each risk factor based on the β-value of the corresponding regression coefficient. A predictive risk-scoring model involving +1q21 was then developed, utilizing the total score derived from these weight scores. The model's discriminative ability was evaluated using the AUC in both the training and validation sets. Finally, we compared the performance of the +1q21-involved risk with the established R-ISS and R2-ISS models.
Upon initial diagnosis, 159 patients (43.32%) exhibited +1q21, with 94 (59.11%) having three copies, referred to as Gain(1q21), and 65 (40.89%) possessing four or more copies, referred to as Amp (1q21). Both were significantly linked to a reduced PFS in myeloma (p < 0.05), which could be effectively mitigated by ASCT. The +1q21-involved risk model, with an AUC of 0.697 in the training set and 0.725 in the validation set, was constructed including Gain(1q21), Amp(1q21), no-ASCT, and TP53 deletion. This model, termed the ultra-high-risk (UHR) model, demonstrated superior performance in predicting shorter PFS compared to the R-ISS stage 3 and R2-ISS stage 4.
The UHR model, which integrates the presence of +1q21 with no-ASCT and TP53 deletion, is designed to identify the early relapse subgroup among patients with +1q21 in NDMM.
染色体 1q 增益和扩增(+1q21)在新诊断的多发性骨髓瘤(NDMM)患者中经常观察到。然而,有效地实施源自 1q21 异常的高危(HR)预后意义的解释仍然具有挑战性。
在对 367 例有症状 MM 患者的综合分析中,我们使用 FISH 以 7.4%的阈值评估了+1q21 的预后意义。患者队列被随机分为训练集(66.5%,n=244)和验证集(33.5%,n=133)。进行了多变量 Cox 回归分析,以确定与 PFS 相关的显著预后因素。根据相应回归系数的β值为每个风险因素分配权重得分。然后,基于这些权重得分,开发了一种涉及+1q21 的预测风险评分模型。使用来自这些权重得分的总分来评估模型的判别能力。在训练集和验证集中分别评估 AUC 以评估模型的区分能力。最后,我们比较了涉及+1q21 的风险与既定的 R-ISS 和 R2-ISS 模型的性能。
在初诊时,159 例患者(43.32%)表现出+1q21,其中 94 例(59.11%)有三个拷贝,称为增益(1q21),65 例(40.89%)有四个或更多拷贝,称为扩增(1q21)。两者均与骨髓瘤中的 PFS 降低显著相关(p<0.05),ASCT 可有效减轻。包含 Gain(1q21)、Amp(1q21)、无 ASCT 和 TP53 缺失的+1q21 相关风险模型在训练集中的 AUC 为 0.697,在验证集中为 0.725。该模型称为超高风险(UHR)模型,与 R-ISS 3 期和 R2-ISS 4 期相比,在预测较短的 PFS 方面表现出更好的性能。
UHR 模型将+1q21 与无 ASCT 和 TP53 缺失相结合,旨在识别 NDMM 中+1q21 患者的早期复发亚组。