蛋白酶体抑制剂和 IMiDs 可克服多发性骨髓瘤中的一些高危细胞遗传学异常，但不能获得 1q21 异常。
Proteasome inhibitors and IMiDs can overcome some high-risk cytogenetics in multiple myeloma but not gain 1q21.
机构信息
Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
KG Jebsen Center for Myeloma Research, Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
出版信息
Eur J Haematol. 2016 Jan;96(1):46-54. doi: 10.1111/ejh.12546. Epub 2015 Jun 29.
Chromosomal aberrations have significant prognostic importance in multiple myeloma (MM). However, proteasome inhibitors (PI) and IMiDs may partly overcome the poor prognostic impact of some of them. In this study, we investigated a population-based consecutive cohort newly diagnosed patients with MM admitted during a defined time period to hospitals in Denmark, Norway, and Sweden. The impact of treatment modality on the prognostic importance of specific chromosomal aberration was investigated, with special reference to gain 1q21. The median follow-up of patients still alive at analysis was 40 months for the high-dose (HDT)-treated ones and 29 months for the whole population. Three hundred forty-seven patients with a known 1q21 status were included in this study. The 347 patients were divided into three groups, that is, 119 patients with the 1q21 gain, 105 patients with other aberrations (OA), that is, del(13q), del(17p), t(4,14), and/or (14;16), and 123 patients with no aberrations (NA). The groups were compared in terms of overall survival (OS), time to progression (TTP), and response. The 3-yr OS for patients with gain 1q21 was 60% compared to patients with OA 74% and NO 82% (gain 1q21 vs. NO P < 0.001; gain 1q21 vs. OA P = 0.095). If treated with PI or IMiDs, the 3-yr OS was 58% for patients with gain 1q21 compared to patients with OA 78% and NO 78%, respectively (P = 0.041, P = 0.140). In HDT patients, the 3-yr OS was 69% for patients with gain 1q21 compared to patients with OA 84% and NO 88%, respectively (P < 0.008, P = 0.600). Thus, neither HDT nor using PI or IMiDs could overcome the poor prognostic impact of gain 1q21, while these drugs and HDT seemed to improve OS in patients with OA, approaching the survival in NO. Further, gain 1q21 appears to be one of the most important poor prognostic chromosomal aberrations in multiple myeloma with current treatments. Trials using new drugs or allogeneic transplantation are warranted.
染色体异常在多发性骨髓瘤（MM）中具有重要的预后意义。然而，蛋白酶体抑制剂（PI）和 IMiDs 可能部分克服其中一些异常的不良预后影响。在这项研究中，我们调查了丹麦、挪威和瑞典医院在规定时间内新诊断为 MM 的连续队列人群。研究了治疗方式对特定染色体异常预后重要性的影响，特别关注 1q21 的增益。在分析时，仍存活的患者中位随访时间为接受高剂量（HDT）治疗者 40 个月，全人群为 29 个月。本研究共纳入 347 例已知 1q21 状态的患者。347 例患者分为三组，即 119 例 1q21 增益患者、105 例其他异常（OA）患者，即 del(13q)、del(17p)、t(4,14)和/或（14;16），以及 123 例无异常（NA）患者。比较三组患者的总生存（OS）、进展时间（TTP）和反应。1q21 增益患者的 3 年 OS 为 60%，OA 患者为 74%，NO 患者为 82%（1q21 增益与 NO，P<0.001；1q21 增益与 OA，P=0.095）。如果接受 PI 或 IMiDs 治疗，1q21 增益患者的 3 年 OS 为 58%，OA 患者为 78%，NO 患者为 78%（P=0.041，P=0.140）。在 HDT 患者中，1q21 增益患者的 3 年 OS 为 69%，OA 患者为 84%，NO 患者为 88%（P<0.008，P=0.600）。因此，HDT 或使用 PI 或 IMiDs 均不能克服 1q21 增益的不良预后影响，而这些药物和 HDT 似乎改善了 OA 患者的 OS，接近 NO 患者的生存。此外，1q21 增益似乎是多发性骨髓瘤中当前治疗方法中最重要的不良预后染色体异常之一。需要进行新药物或同种异体移植的试验。
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