Marcoux Curtis, Pasvolsky Oren, Milton Denái R, Tanner Mark R, Bashir Qaiser, Srour Samer, Saini Neeraj, Lin Paul, Ramdial Jeremy, Nieto Yago, Tang Guilin, Lee Hans C, Patel Krina K, Kebriaei Partow, Ahmed Amna, Aljawai Yosra, Thomas Sheeba K, Orlowski Robert Z, Shpall Elizabeth J, Champlin Richard E, Qazilbash Muzaffar H
Division of Hematology, Dalhousie University, Halifax, Canada.
Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Transplant Cell Ther. 2025 Jan;31(1):12.e1-12.e10. doi: 10.1016/j.jtct.2024.10.011. Epub 2024 Oct 22.
Despite tremendous advancements in multiple myeloma (MM) therapeutics, outcomes remain heterogeneous, heavily influenced by clinical and cytogenetic factors. Among these, deletion of the short arm of chromosome 17 (del(17p)) is a strong predictor of poor prognosis. The aim of this study was to evaluate real-world outcomes in patients with newly diagnosed MM (NDMM) with del(17p) undergoing upfront autologous hematopoietic stem cell transplantation (auto-HCT). We conducted a single-center retrospective analysis of patients with NDMM who underwent upfront auto-HCT at MD Anderson Cancer Center between 2008 and 2018. Primary endpoints were progression-free survival (PFS) and overall survival (OS), with secondary endpoints being hematological response and measurable residual disease (MRD) status postauto-HCT. MRD status in the bone marrow biopsy was evaluated using 8-color next-generation flow cytometry with a sensitivity of 1/10 cells. One hundred and fifteen patients were included (55% male). Median age at auto-HCT was 62 years (range 34 to 83). The median del(17p) clone size was 20%, with 51 (53%) patients having clone sizes >20% and 15 (15%) patients having clone sizes >55%. Additional high-risk cytogenetic abnormalities included t(4;14) in 15 (13%) patients, t(14;16) in 8 (7%) patients, and 1q21+ in 25 (22%) patients. After induction, 10% of patients achieved ≥ CR, and 50% achieved ≥ VGPR, with 25% having MRD-negative ≥ VGPR. Post-transplant, 42% achieved ≥ CR, and 83% achieved ≥ VGPR as best response, with 55% (48/87) having MRD-negative ≥ VGPR. With a median follow-up of 31.4 months (range 3.1 to 199.1), median PFS and OS for the entire cohort were 19.9 and 71.5 months, respectively, and 5-year OS was 53%. Concurrent del(17p) and t(4;14) were associated with significantly worse outcomes, with median PFS and OS of 11.5 and 22.4 months, respectively. In multivariable analysis (MVA), female sex was associated with worse PFS (HR [95% CI] 2.87 [1.75 to 4.72], P < .001), while MRD negative CR post-transplant (0.35 [0.18 to 0.68], P = .002) and maintenance therapy (0.46 [0.27 to 0.77], P = 0.003) were associated with better PFS. In MVA for OS, female sex (2.22 [1.18 to 4.17], P = 0.013) and the presence of t(4;14) (2.55 [1.09 to 5.95], P = 0.030) were associated with worse OS, whereas Karnofsky Performance Status of ≥90 (0.47 [0.23 to 0.94], P = 0.034) was associated with better OS. This study affirms del(17p) as a high-risk abnormality with unfavorable outcomes despite modern therapies. The co-occurrence of del(17p) and t(4;14) was associated with particularly poor outcomes. Novel approaches are needed for this high-risk subgroup.
尽管多发性骨髓瘤（MM）治疗取得了巨大进展，但治疗结果仍存在异质性，受到临床和细胞遗传学因素的严重影响。其中，17号染色体短臂缺失（del(17p)）是预后不良的有力预测指标。本研究的目的是评估新诊断的伴有del(17p)的MM（NDMM）患者接受 upfront 自体造血干细胞移植（auto-HCT）后的真实世界治疗结果。我们对2008年至2018年在MD安德森癌症中心接受 upfront auto-HCT的NDMM患者进行了单中心回顾性分析。主要终点是无进展生存期（PFS）和总生存期（OS），次要终点是血液学缓解以及auto-HCT后的可测量残留病（MRD）状态。使用灵敏度为1/10细胞的8色下一代流式细胞术评估骨髓活检中的MRD状态。纳入了115例患者（55%为男性）。auto-HCT时的中位年龄为62岁（范围34至83岁）。del(17p)克隆大小的中位数为20%，51例（53%）患者的克隆大小>20%，15例（15%）患者的克隆大小>55%。其他高危细胞遗传学异常包括15例（13%）患者的t(4;14)、8例（7%）患者的t(14;16)和25例（22%）患者的1q21+。诱导治疗后，10%的患者达到≥完全缓解（CR），50%的患者达到≥非常好的部分缓解（VGPR），25%的患者为MRD阴性且≥VGPR。移植后，42%的患者达到≥CR，83%的患者达到≥VGPR作为最佳缓解，55%（48/87）的患者为MRD阴性且≥VGPR。中位随访31.4个月（范围3.1至199.1个月），整个队列的中位PFS和OS分别为19.9个月和71.5个月，5年总生存率为53%。del(17p)和t(4;14)同时存在与显著更差的结果相关，中位PFS和OS分别为11.5个月和22.4个月。在多变量分析（MVA）中，女性与更差的PFS相关（风险比[95%置信区间]2.87[1.75至4.72]，P<.001），而移植后MRD阴性CR（0.35[0.18至0.68]，P=.002）和维持治疗（0.46[0.27至0.77]，P = 0.003）与更好的PFS相关。在OS的MVA中，女性（2.22[1.18至4.17]，P = 0.013）和t(4;14)的存在（2.55[1.09至5.95]，P = 0.030）与更差的OS相关，而卡氏功能状态≥90（0.47[0.23至0.94]，P = 0.034）与更好的OS相关。本研究证实del(17p)是一种高危异常，尽管有现代治疗方法，但预后不良。del(17p)和t(4;14)同时存在与特别差的结果相关。对于这个高危亚组需要新的治疗方法。
