伊布替尼治疗复发/难治原发性自身免疫性溶血性贫血二例——探索性研究

Ibrutinib treatment for 2 cases of relapsed/refractory autoimmune hemolytic anemia: a pilot study

目的探索伊布替尼治疗复发/难治原发性自身免疫性溶血性贫血(AIHA)的疗效及安全性。方法2例原发性AIHA患者多次复发,1例有脾切除史,经糖皮质激素、利妥昔单抗及多种免疫抑制药物治疗无效,诊断为复发/难治原发性AIHA。给予伊布替尼起始剂量280 mg/d(例1第3~8周加量到420 mg/d)治疗,观察疗效及安全性。结果例1治疗2周后脱离输血,HGB增长>20 g/L,获得部分疗效;10周后HGB 113 g/L伴有代偿性溶血实验室改变,获得完全缓解伴代偿性溶血状态(CRi)。例2治疗2周后脱离输血,HGB增长>20 g/L,获得部分疗效;6周后HGB 118 g/L伴有代偿性溶血实验室改变,获得CRi。2例患者分别随访16周和12周,已维持疗效14周和10周,未复发。伊布替尼治疗期间2例患者血液学不良反应轻,非血液学不良反应轻微。结论伊布替尼单药治疗复发/难治原发性AIHA有初步疗效,尚需规范的临床研究试验进一步验证其疗效及安全性。

Objective To explore the efficacy and safety of ibrutinib treatment for relapsed/refractory(R/R)primary autoimmune hemolytic anemia(AIHA).Methods Two cases of primary AIHA with relapse events were refractory to glucocorticoid,anti-CD20 monoclonal antibody,immunosuppressive drugs,and splenectomy(case 1 only).Ibrutinib treatment was administered at an initial dose of 280 mg/d(420 mg/d for case 1 from the 3rd to 8th week).Results Both patients achieved transfusion independence and HGB>20 g/L above baseline after 2 weeks(partial response).For case 1,HGB concentration restored to 113 g/L but with incomplete hemolysis recovery after 10 weeks;HGB reached the level of 118 g/L,also with incomplete hemolysis recovery,after 6 weeks in case 2.They all acquired complete response with incomplete hemolysis recovery(CRi).The responses sustained 14 weeks and 10 weeks after follow-up at 16 weeks and 12 weeks,respectively.During the treatment,hematologic and nonhematologic toxicity is mild and acceptable.Conclusion Ibrutinib alone is effective for the 2 R/R primary AIHA cases.We need further clinical trial to identify its efficacy and safety.