Double-deletion of 1p32 defines ultra-high-risk myeloma, but monoallelic del(1p32) remains a strong prognostic factor

Cytogenetics abnormalities (CA) are known to be the preponderant prognostic factor in multiple myeloma (MM). Our team has recently developeda prognostic score based on 6 CA, where del(1p32) appears to be the second worst abnormality after del(17p). The aim of this study was to confirm the adverse impact of 1p32 deletion on newly-diagnosed multiple myeloma (NDMM) patients. Among 2551 NDMM patients, 11% were harboring del(1p32). Their overall survival (OS) was half as long as the OS of patients without del(1p32) (49 months vs. 124 months). Likewise, progression-free survival was significantly shorter. More importantly, double-deletion of the 1p32 locus conferred a dramatically poorer prognosis than a monoallelic del(1p32) (OS: 25 months vs. 60 months). As expected, the OS of del(1p32) patients significantly decreased when this abnormality was associated with other high-risk CA (del(17p), t(4;14) or gain(1q)). In the multivariate analysis, del(1p32) appeared as a negative prognostic factor; after adjustment for age and treatment, the risk of progression was 1.3 times higher among patients harboring del(1p32), and the risk of death was 1.9 times higher. At the dawn of risk-adapted treatment strategies, we have confirmed the adverse impact of del(1p32) in MM and the relevance of its assessment at diagnosis. Clinical data were obtained from 2551 NDMM patients recruited within hospitals involved in the Intergroupe Francophone du Myélome, followed up for ≥ 36 months or having died or progressed within 36 months post-treatment. The diagnosis was established between 2010 and 2021, and 1258 patients were treated with intensive therapy. PCs were analyzed either by FISH (848 patients), SNP array (1395 patients) or by NGS (308 patients), depending on the date of receipt. We compared survival and characteristics of patients according to del(1p32) status (282 patients harboring del(1p32) versus 2,269 control patients.

细胞遗传学异常（Cytogenetics Abnormalities，缩写CA）是多发性骨髓瘤（Multiple Myeloma，缩写MM）的首要预后影响因素。本团队近期开发了一项基于6项细胞遗传学异常的预后评分系统，其中1p32缺失（del(1p32)）是仅次于17p缺失（del(17p)）的不良预后异常类型。本研究旨在证实1p32缺失对初诊多发性骨髓瘤（Newly Diagnosed Multiple Myeloma，缩写NDMM）患者的不良预后影响。

本研究共纳入2551例初诊多发性骨髓瘤患者，其中11%携带1p32缺失。该类患者的总生存期（Overall Survival，缩写OS）仅为未携带该异常患者的一半（49个月 vs 124个月）；其无进展生存期亦显著缩短。更为关键的是，1p32位点双缺失患者的预后远差于单等位基因1p32缺失患者（总生存期：25个月 vs 60个月）。

正如预期，当1p32缺失合并其他高危细胞遗传学异常（17p缺失、t(4;14)易位或1q扩增（gain(1q)））时，携带1p32缺失的患者总生存期会显著降低。多变量分析结果显示，1p32缺失为独立的不良预后因素；在校正年龄与治疗方案后，携带1p32缺失的患者疾病进展风险升高1.3倍，死亡风险升高1.9倍。

在风险适应性治疗策略日益普及的当下，本研究证实了1p32缺失对多发性骨髓瘤患者的不良预后影响，以及在诊断时对该异常进行检测的临床价值。

本研究的临床数据来源于法语骨髓瘤协作组（Intergroupe Francophone du Myélome）旗下多家医院招募的2551例初诊多发性骨髓瘤患者，所有患者均完成至少36个月的随访，或在治疗后36个月内出现死亡或疾病进展。患者的确诊时间为2010年至2021年，其中1258例患者接受了强化治疗。

根据样本接收时间的不同，研究人员采用荧光原位杂交（Fluorescence In Situ Hybridization，缩写FISH，848例患者）、单核苷酸多态性芯片（Single Nucleotide Polymorphism Array，缩写SNP array，1395例患者）或下一代测序（Next-Generation Sequencing，缩写NGS，308例患者）对浆细胞（Plasma Cells，缩写PCs）进行检测。

研究人员根据是否携带1p32缺失对患者的生存期与临床特征进行了对比分析：282例携带1p32缺失的患者作为病例组，2269例患者作为对照组。