Saunders Brendan, Theodorakakou Foteini, Fotiou Despina, Boullt Samuel, Evans Benjamin, Dimopoulos Meletios A, Kastritis Efstathios, Bianchi Giada
Amyloidosis Program, Division of Hematology, Brigham and Women's Hospital, Boston, MA.
Department of Clinical Therapeutics, National Kapodistrian University of Athens, Athens, Greece.
Blood Adv. 2025 Aug 12;9(15):3771-3779. doi: 10.1182/bloodadvances.2024015528.
A difference between involved and uninvolved free light chains (dFLC) ≥180 mg/L is part of the 2012 Mayo staging system for amyloid light chain (AL) amyloidosis given its negative impact on overall survival (OS). However, none of the 758 patients evaluated to develop and validate this staging system received bortezomib or daratumumab-containing regimens. Over the past 2 decades, cyclophosphamide-bortezomib-dexamethasone (CyBorD) and, more recently, daratumumab-CyBorD (DaraCyBorD) have become cornerstone treatments for AL amyloidosis, demonstrating high efficacy in rapidly normalizing FLC levels. We hypothesized that, in patients with newly diagnosed AL amyloidosis treated with bortezomib- and daratumumab-based regimens, a baseline high FLC burden may no longer predict adverse prognosis. In this retrospective, multicenter study of 223 patients with newly diagnosed AL amyloidosis treated with CyBorD or DaraCyBorD therapy, we investigated (1) the association between baseline involved FLC and dFLC hematologic response at 28 days and 3, 6, 9, and 12 months after the commencement of therapy; (2) the OS of patients with baseline low (<180 mg/L), medium (180-400 mg/L), and high (>400 mg/L) dFLC; and (3) the prognostic value of bone marrow plasma cell burden in determining response to CyBorD or DaraCyBorD therapy and OS and, finally, the prognostic value of the 2012 Mayo staging system in the CyBorD and DaraCyBorD cohorts. Our findings suggest that a dFLC of >180 mg/L no longer holds prognostic value in the era of CyBorD/DaraCyBorD-based AL amyloidosis therapy and question the utility of the Mayo 2012 staging system in the era of highly effective chemoimmunotherapies.
受累与未受累游离轻链差值（dFLC）≥180 mg/L是2012年梅奥淀粉样轻链（AL）淀粉样变性分期系统的一部分，因其对总生存期（OS）有负面影响。然而，参与制定和验证该分期系统的758例患者中，没有一人接受过含硼替佐米或达雷妥尤单抗的方案。在过去20年中，环磷酰胺-硼替佐米-地塞米松（CyBorD），以及最近的达雷妥尤单抗-CyBorD（DaraCyBorD）已成为AL淀粉样变性的基础治疗方案，在使游离轻链（FLC）水平迅速恢复正常方面显示出高效能。我们推测，在接受基于硼替佐米和达雷妥尤单抗方案治疗的新诊断AL淀粉样变性患者中，基线FLC负担较高可能不再预示不良预后。在这项对223例接受CyBorD或DaraCyBorD治疗的新诊断AL淀粉样变性患者的回顾性多中心研究中，我们调查了：（1）基线受累FLC与治疗开始后28天及3、6、9和12个月时dFLC血液学反应之间的关联；（2）基线dFLC低（<180 mg/L）、中（180 - 400 mg/L）和高（>400 mg/L）患者的总生存期；（3）骨髓浆细胞负担在确定对CyBorD或DaraCyBorD治疗的反应及总生存期方面的预后价值，以及最后，2012年梅奥分期系统在CyBorD和DaraCyBorD队列中的预后价值。我们的研究结果表明，在基于CyBorD/DaraCyBorD的AL淀粉样变性治疗时代，dFLC>180 mg/L不再具有预后价值，并对梅奥2012分期系统在高效化学免疫疗法时代的实用性提出质疑。
