Chung Alfred, Kaufman Gregory P, Sidana Surbhi, Eckhert Erik, Schrier Stanley L, Lafayette Richard A, Arai Sally, Witteles Ronald M, Liedtke Michaela
Deparment of Medicine, Stanford University School of Medicine, Stanford, CA and.
Department of Lymphoma and Myeloma, MD Anderson Cancer Center, Houston, TX.
Blood Adv. 2020 Feb 11;4(3):458-466. doi: 10.1182/bloodadvances.2019000776.
Immunoglobulin light chain amyloidosis (AL amyloidosis) involves deposition of abnormally folded light chains into a wide range of tissues causing organ dysfunction, including in the heart and kidney. Daratumumab, a CD38-targeted antibody, has recently demonstrated efficacy in producing hematologic responses in previously treated disease. However, data on survival outcomes and organ responses to daratumumab are lacking. Seventy-two patients with previously treated AL amyloidosis who received daratumumab monotherapy with dexamethasone were retrospectively evaluated. With a median follow-up of 27 months, 2-year overall survival (OS) was 86.9% (median OS, not reached) and 2-year time-to-next treatment or death (TTNT)-free survival was 62% (median TTNT, not reached). Forty of 52 evaluable patients achieved a hematologic response (77%), with >60% of patients achieving a very good partial response or better; median time-to-hematologic response was 1 month. Fifty-seven patients (79%) had cardiac involvement, and 55% of evaluable patients achieved a cardiac response, with a median response time of 3.2 months among responders. Cardiac responses were associated with an improvement in OS, with landmark analysis for cardiac responses at 3 months trending toward statistical significance (100% vs 55% at 30 months, P = .051). Forty-seven patients (65%) had renal involvement, and 52% of evaluable patients achieved a renal response, with a median response time of 6 months among responders; there was no significant difference in OS between renal responders and nonresponders. This study demonstrates that daratumumab is highly effective in the treatment of previously treated AL amyloidosis, and a significant proportion of patients can achieve deep hematologic responses, as well as improvements in organ function.
免疫球蛋白轻链淀粉样变性（AL淀粉样变性）涉及异常折叠的轻链沉积于多种组织，导致器官功能障碍，包括心脏和肾脏。达雷妥尤单抗是一种靶向CD38的抗体，最近已证明其在既往治疗的疾病中产生血液学反应方面具有疗效。然而，关于达雷妥尤单抗的生存结果和器官反应的数据尚缺乏。对72例接受达雷妥尤单抗单药联合地塞米松治疗的既往治疗的AL淀粉样变性患者进行了回顾性评估。中位随访27个月，2年总生存率（OS）为86.9%（中位OS未达到），2年无下次治疗或死亡时间（TTNT）生存率为62%（中位TTNT未达到）。52例可评估患者中有40例获得血液学反应（77%），超过60%的患者获得非常好的部分反应或更好反应；血液学反应的中位时间为1个月。57例患者（79%）有心脏受累，55%的可评估患者获得心脏反应，反应者的中位反应时间为3.2个月。心脏反应与OS改善相关，3个月时心脏反应的标志性分析有统计学意义的趋势（30个月时为100%对55%，P = 0.051）。47例患者（65%）有肾脏受累，52%的可评估患者获得肾脏反应，反应者的中位反应时间为6个月；肾脏反应者和无反应者的OS无显著差异。本研究表明，达雷妥尤单抗在治疗既往治疗的AL淀粉样变性方面非常有效，且相当比例的患者可实现深度血液学反应以及器官功能改善。
