da Fonseca Ana Rita, Justino Caio Cesar, Campos de Molla Vinicius, Yamakawa Patricia Eiko, Rabelo Iara Baldim, Arnold Louise, Kelly Richard, Griffin Morag, Munir Talha, Hill Anita, Velloso Elvira, Dalessandro Thales, Risitano Antonio M, Scheinberg Phillip, Kulasekararaj Austin, Arrais-Rodrigues Celso
Department of Clinical and Experimental Hematology, Universidade Federal de São Paulo, São Paulo, Brazil.
Hospital Sírio Libanês, São Paulo, Brazil.
Blood Adv. 2025 Feb 25;9(4):906-912. doi: 10.1182/bloodadvances.2024014159.
Immunosuppressive therapy using horse antithymocyte globulin (ATG; h-ATG) combined with cyclosporine (CsA) and eltrombopag is the standard care for aplastic anemia (AA) in patients without a suitable matched donor. However, in many countries, h-ATG use has been discontinued, leaving rabbit ATG (r-ATG), which has a lower response rates and poorer survival, as the only alternative. In previous studies, alemtuzumab (ALZ), a humanized monoclonal antibody targeting CD52, combined with CsA, resulted in an adequate overall response rate (ORR) in patients with AA. This study describes a multicenter, international retrospective analysis of ALZ for treating AA.We analyzed a series of patients who received subcutaneous ALZ for AA in 4 centers in Brazil and the United Kingdom from March 2009 to January 2024. We analyzed 64 ALZ treatments in 61 adult patients with AA, 76% with severe AA (SAA) or very SAA. The ORR was 59.4% at 12 months (complete, 21.9%; partial, 37.5%). Cumulative incidence (CI) of response was 54.7% at 6 months and 59.4% at 12 months. Younger patients (age <65 years) had higher CI of response (67% vs 31%; P = .03), as did patients treated with a total dose of 103 mg (70% vs 38%; P = .02). Overall survival was 86% at 1 year, 78% at 2 years, and 70% at 4 years, significantly higher in responders (90% vs 44%; P < .0001). Adverse events were of low grade, and infectious events were infrequent. Subcutaneous ALZ is a feasible, effective, and safe alternative to r-ATG for patients with AA requiring immunosuppressive treatment when h-ATG access is limited.
使用马抗胸腺细胞球蛋白（ATG；h-ATG）联合环孢素（CsA）和艾曲泊帕进行免疫抑制治疗是无合适匹配供体的再生障碍性贫血（AA）患者的标准治疗方法。然而，在许多国家，h-ATG的使用已被停止，使得兔ATG（r-ATG）成为唯一的替代选择，但其缓解率较低且生存率较差。在先前的研究中，靶向CD52的人源化单克隆抗体阿仑单抗（ALZ）联合CsA，在AA患者中产生了足够的总缓解率（ORR）。本研究描述了一项关于ALZ治疗AA的多中心、国际回顾性分析。我们分析了2009年3月至2024年1月在巴西和英国4个中心接受皮下注射ALZ治疗AA的一系列患者。我们分析了61例成年AA患者的64次ALZ治疗，其中76%为重度AA（SAA）或极重度AA。12个月时的ORR为59.4%（完全缓解，21.9%；部分缓解，37.5%）。6个月时缓解的累积发生率（CI）为54.7%，12个月时为59.4%。年轻患者（年龄<65岁）的缓解CI较高（67%对31%；P = 0.03），接受总剂量103 mg治疗的患者也是如此（70%对38%；P = 0.02）。1年总生存率为86%，2年为78%，4年为70%，缓解者的生存率显著更高（90%对44%；P < 0.0001）。不良事件为低级别，感染事件很少见。对于h-ATG获取受限且需要免疫抑制治疗的AA患者，皮下注射ALZ是r-ATG的一种可行、有效且安全的替代方法。
