Treatment of relapsed or refractory acute myeloid leukemia with humanized anti-D33 monoclonal antibody HuM195
Treatment of relapsed or refractory acute myeloid leukemia with humanized anti-D33 monoclonal antibody HuM195
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DOI：
10.1038/sj.leu.2402803
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发表时间：
2003-02-01
期刊：
影响因子：
11.4
通讯作者：
Wedel, N
中科院分区：
文献类型：
--
作者：
Feldman, E;Kalaycio, M;Wedel, N
HuM 195是一种人源化、未缀合的抗CD 33单克隆抗体。50例复发性或难治性AML成人患者随机接受HuM 195，剂量为12或36 mg/m2，在第1-4天和第15-18天静脉输注4小时。病情稳定或缓解的患者在第29-32天和第43-46天再接受两个周期。24例患者给予HuM 195作为首次挽救治疗，26例患者给予HuM 195作为第二次或后续挽救治疗。20例患者治疗前骨髓原始细胞百分比在5 - 30%之间，其他患者的原始细胞计数大于30%。患者的中位年龄为62岁（范围为26-86岁），在95%的免疫分型患者中检测到CD 33。在49例可评价患者中，观察到2例完全缓解和1例部分缓解。所有三种反应都发生在接受12 mg/m2剂量水平治疗的患者中，并且所有患者的基线原始细胞百分比均低于30%。在另外9名患者中观察到原始细胞计数下降30 - 74%。大多数患者发生输注相关发热和寒战事件，通常为轻度，主要与首次抗体给药相关。未观察到肝、肾或心脏毒性，其他不良事件如恶心、呕吐、粘膜炎和腹泻不常见或认为与HuM 195无关。此外，未检测到抗HuM 195应答。HuM 195作为单一药物在复发性或难治性AML患者中具有最小但可观察到的抗白血病活性，并且活性仅限于低负担疾病患者。在两种剂量水平的抗体之间未观察到临床功效或毒性的显著差异。HuM 195耐受性良好，主要毒性为输注相关发热和寒战。这种未偶联的单克隆抗体的有意义的临床疗效可能仅在具有微小残留疾病的患者中实现，或与化疗联合使用。
HuM195 is a humanized, unconjugated, anti-CD33 monoclonal antibody. Fifty adult patients with relapsed or refractory AML were randomized to receive HuM195 at a dose of 12 or 36 mg/m(2) by intravenous infusion over 4 h on days 1-4 and 15-18. Patients with stable or responding disease received two additional cycles on days 29-32 and 43-46. HuM195 was given as first salvage therapy in 24 patients and as second or subsequent salvage therapy in 26 patients. Pretreatment blast percentage in the marrow was between 5 and 30% in 20 patients with the others having blast counts greater than 30%. The median age of patients was 62 years (range 26-86) and CD33 was detected in 95% of patients for whom immunophenotyping was available. Of 49 evaluable patients, two complete and one partial remission were observed. All three responses were in patients treated at the 12 mg/m(2) dose level and all had baseline blast percentages less than 30%. Decreases in blast counts ranging from 30 to 74% were seen in nine additional patients. Infusion-related events of fever and chills occurred in the majority of patients and were generally mild and primarily related to the first dose of antibody. No hepatic, renal or cardiac toxicities were observed and other adverse events such as nausea, vomiting, mucositis and diarrhea were uncommon or felt to be unrelated to HuM195. In addition, anti-HuM195 responses were not detected. HuM195 as a single agent has minimal, but observable, anti-leukemic activity in patients with relapsed or refractory AML and activity is confined to patients with low burden disease. No significant differences in clinical efficacy or toxicity were seen between the two dose levels of antibody. HuM195 was well tolerated with infusion-related fevers and chills the predominant toxicities seen. Meaningful clinical efficacy of this unconjugated monoclonal antibody may be realized only in patients with minimal residual disease, or in combination with chemotherapy.