Kündgen Lea Jasmin, Akhoundova Dilara, Hoffmann Michele, Legros Myriam, Shaforostova Inna, Seipel Katja, Bacher Ulrike, Pabst Thomas
Department of Medical Oncology, Inselspital, University of Bern, CH-3010 Bern, Switzerland.
Department of Clinical Chemistry, Inselspital, University of Bern, CH-3010 Bern, Switzerland.
Cancers (Basel). 2025 May 4;17(9):1565. doi: 10.3390/cancers17091565.
Cytogenetic abnormalities and the persistence of minimal residual disease (MRD) following autologous stem cell transplantation (ASCT) are two established prognostically unfavorable biomarkers in multiple myeloma (MM). Previous studies have shown that post-transplant MRD status is a powerful predictor of progression-free survival (PFS) and overall survival (OS). However, the impact of MRD remains poorly characterized in MM patients with high- or ultra-high-risk cytogenetics. This study investigated the prognostic value of post-transplant MRD in standard- versus high- and ultra-high-risk MM. To this aim, we performed a retrospective analysis of 137 MM patients who underwent high-dose chemotherapy (HDCT) and ASCT at our institution between January 2019 and December 2021. Cytogenetics were assessed by fluorescence in situ hybridization. High-risk genomic alterations included del(17p), t(4;14), t(14;16), t(14;20), gain(1q), and mutations, with two or more alterations defining the ultra-high-risk category. MRD was assessed in bone marrow aspirates post-ASCT using flow cytometry. Eighty-two (60%) patients were categorized as being at standard risk, forty (29%) as high risk, and fifteen (11%) as ultra-high risk. Median follow-up was 47 months. MRD negativity was achieved in 76 (55%) patients. At 48 months, the overall PFS rate was 61% (72%, 50%, and 32% for the standard-, high-, and ultra-high-risk subgroups, respectively; = 0.0004), while the OS rate was 85% (89%, 79%, and 80% in standard-, high-, and ultra-high-risk MM patients, respectively; = 0.1494). Within the standard-risk subgroup, longer PFS was observed for patients achieving MRD negativity ( = 0.0172). High- and ultra-high-risk patients showed no significant differences in PFS when stratified by MRD status, possibly due to prompt progression to MRD positivity. Our results suggest that high- and ultra-high-risk MM patients might benefit from closer response monitoring, including dynamic MRD assessment. Further, high- and ultra-high-risk patients might require a more intensive peri-transplant treatment.
细胞遗传学异常和自体干细胞移植（ASCT）后微小残留病（MRD）的持续存在是多发性骨髓瘤（MM）中两个已确定的预后不良生物标志物。先前的研究表明，移植后MRD状态是无进展生存期（PFS）和总生存期（OS）的有力预测指标。然而，在具有高风险或超高风险细胞遗传学的MM患者中，MRD的影响仍未得到充分描述。本研究调查了移植后MRD在标准风险与高风险和超高风险MM中的预后价值。为此，我们对2019年1月至2021年12月在我们机构接受大剂量化疗（HDCT）和ASCT的137例MM患者进行了回顾性分析。通过荧光原位杂交评估细胞遗传学。高风险基因组改变包括del(17p)、t(4;14)、t(14;16)、t(14;20)、1q增益和突变，两种或更多种改变定义为超高风险类别。使用流式细胞术在ASCT后的骨髓穿刺物中评估MRD。82例（60%）患者被分类为标准风险，40例（29%）为高风险，15例（11%）为超高风险。中位随访时间为47个月。76例（55%）患者实现了MRD阴性。在48个月时，总体PFS率为61%（标准风险、高风险和超高风险亚组分别为7:2%、50%和32%；P = 0.0004），而OS率为85%（标准风险、高风险和超高风险MM患者分别为89%、79%和80%；P = 0.1494）。在标准风险亚组中，实现MRD阴性的患者观察到更长的PFS（P = 0.0172）。当按MRD状态分层时，高风险和超高风险患者在PFS方面没有显著差异，可能是由于迅速进展为MRD阳性。我们的结果表明，高风险和超高风险MM患者可能受益于更密切的反应监测，包括动态MRD评估。此外，高风险和超高风险患者可能需要更强化的移植周围治疗。
