Arnall Justin R, Usmani Saad Z, Adamu Hawawu, Mishkin Joseph, Bhutani Manisha
1 Department of Pharmacy, Levine Cancer Institute, Atrium Health, Charlotte, NC, USA.
2 Department of Hematologic Oncology and Blood Disorders, Levine Cancer Institute, Atrium Health, Charlotte, NC, USA.
J Oncol Pharm Pract. 2019 Jun;25(4):1021-1025. doi: 10.1177/1078155218815305. Epub 2018 Nov 26.
Systemic light-chain (AL) amyloidosis is a rare hematologic disorder where proteins infiltrate tissues leading to organ failure and death. Cardiac involvement, present in ∼70% of patients, determines stage and prognosis of the disease, with advanced involvement having a median survival of six months. The treatment of light-chain amyloidosis is directed at recovering organ function with therapeutic strategies following those of multiple myeloma with plasma cell-directed therapies. The use of single agent daratumumab has been reported in light-chain amyloidosis achieving rapid and deep responses. The combination of daratumumab, pomalidomide, and dexamethasone (DaraPomD) is particularly interesting for severe AL based on success in multiple myeloma. A 43-year-old female with light-chain amyloidosis and concomitant multiple myeloma presented with severe bowel dysmotility causing abdominal pain, anemia, and a 100-pound unintentional weight loss. A combination of cyclophosphamide, bortezomib, and dexamethasone was initiated but after five cycles her symptoms were progressing and therapy was switched to DaraPomD to optimize response. At the conclusion of two cycles she had achieved an amyloid complete-hematologic response, with her recurring ileus and abdominal pain significantly improved. Additionally, cardiac markers also suggested a rapid response without a common paradoxical worsening of congestive heart failure, and was overall well tolerated. Given the severe symptoms and refractory nature of our patient's disease DaraPomD was reasonable. With the tolerability and response seen, this patient experience supports a formal clinical trial evaluating the safety and efficacy of DaraPomD in light-chain amyloidosis.
系统性轻链（AL）淀粉样变性是一种罕见的血液系统疾病，蛋白质浸润组织会导致器官衰竭和死亡。约70%的患者存在心脏受累情况，这决定了疾病的分期和预后，晚期受累患者的中位生存期为6个月。轻链淀粉样变性的治疗旨在通过遵循多发性骨髓瘤的治疗策略、采用针对浆细胞的疗法来恢复器官功能。已有报道称，在轻链淀粉样变性中使用单药达雷妥尤单抗可实现快速且深度的缓解。基于在多发性骨髓瘤中的成功经验，达雷妥尤单抗、泊马度胺和地塞米松（DaraPomD）联合方案对于严重的AL尤其值得关注。一名43岁患有轻链淀粉样变性并伴有多发性骨髓瘤的女性，出现严重的肠道运动障碍，导致腹痛、贫血以及100磅的非故意体重减轻。开始使用环磷酰胺、硼替佐米和地塞米松联合治疗，但五个疗程后她的症状仍在进展，于是将治疗方案改为DaraPomD以优化缓解效果。两个疗程结束时，她实现了淀粉样变完全血液学缓解，反复出现的肠梗阻和腹痛明显改善。此外，心脏标志物也显示出快速反应，且没有出现充血性心力衰竭常见的矛盾性恶化情况，总体耐受性良好。鉴于我们患者疾病的严重症状和难治性，DaraPomD方案是合理的。鉴于观察到的耐受性和缓解效果，该患者的经历支持开展一项正式的临床试验，评估DaraPomD在轻链淀粉样变性中的安全性和有效性。
