Sandmann Sarah, Karsch Katharina, Bartel Peter, Exeler Rita, Brix Tobias J, Mai Elias K, Varghese Julian, Lenz Georg, Khandanpour Cyrus
Institute of Medical Informatics, University of Münster, Münster, Germany.
Department of Medicine A, Hematology, Oncology and Pneumology, University Hospital Münster, Münster, Germany.
Front Oncol. 2022 Jul 19;12:919278. doi: 10.3389/fonc.2022.919278. eCollection 2022.
A variety of biomarkers are considered for diagnosis (e.g., β2-microgobulin, albumin, or LDH) and prognosis [e.g., cytogenetic aberrations detected by fluorescence hybridization (FISH)] of multiple myeloma (MM). More recently, clonal evolution has been established as key. Little is known on the clinical implications of clonal evolution.
We performed in-depth analyses of 25 patients with newly diagnosed MM with respect to detailed clinical information analyzing blood samples collected at several time points during follow-up (median follow-up: 3.26 years since first diagnosis). We split our cohort into two subgroups: with and without new FISH clones developing in the course of disease.
Each subgroup showed a characteristic chromosomal profile. Forty-three percent of patients had evidence of appearing new clones. The patients with new clones showed an increased number of translocations affecting chromosomes 14 (78% vs. 33%; = 0.0805) and 11, and alterations in chromosome 4 (amplifications and translocations). New clones, on the contrary, were characterized by alterations affecting chromosome 17. Subsequent to the development of the new clone, 6 out of 9 patients experienced disease progression compared to 3 out of 12 for patients without new clones. Duration of the therapy applied for the longest time was significantly shorter within the group of patients developing new clones (median: 273 vs. 406.5 days; = 0.0465).
We demonstrated that the development of new clones, carrying large-scale alterations, was associated with inferior disease course and shorter response to therapy, possibly affecting progression-free survival and overall survival as well. Further studies evaluating larger cohorts are necessary for the validation of our results.
多种生物标志物被用于多发性骨髓瘤（MM）的诊断（例如，β2微球蛋白、白蛋白或乳酸脱氢酶）和预后评估[例如，通过荧光原位杂交（FISH）检测到的细胞遗传学异常]。最近，克隆进化已被确认为关键因素。关于克隆进化的临床意义，人们知之甚少。
我们对25例新诊断的MM患者进行了深入分析，涉及详细的临床信息，分析了随访期间多个时间点采集的血液样本（自首次诊断起的中位随访时间：3.26年）。我们将队列分为两个亚组：疾病过程中出现新FISH克隆的患者和未出现新FISH克隆的患者。
每个亚组都显示出特征性的染色体图谱。43%的患者有出现新克隆的证据。出现新克隆的患者中，影响14号染色体的易位数量增加（78%对33%；P = 0.0805），还有11号染色体以及4号染色体的改变（扩增和易位）。相反，新克隆的特征是影响17号染色体的改变。新克隆出现后，9例患者中有6例经历了疾病进展，而未出现新克隆的12例患者中有3例经历了疾病进展。在出现新克隆的患者组中，应用时间最长的治疗疗程明显更短（中位值：273天对406.5天；P = 0.0465）。
我们证明，携带大规模改变的新克隆的出现与较差的病程和较短的治疗反应相关，可能也会影响无进展生存期和总生存期。需要进一步评估更大队列的研究来验证我们的结果。
