Abstract：
In this review article we provide a critical insight into recent reports evaluating innovative therapies for warm type autoimmune hemolytic anemia (wAIHA). Among published articles, we selected two reports on the use of the proteasome inhibitor bortezomib in association with dexamethasone or rituximab, one study on the spleen tyrosine kinase inhibitor fostamatinib, and a retrospective study on recombinant erythropoietin (rEPO). Among recent scientific communications, we discussed a report on the phosphoinositide 3-kinase delta inhibitor (PI3Kδi) parsaclisib. All studies highlighted a good efficacy although to be confirmed in larger trials and with limitations due to the heterogeneity of wAIHA patients enrolled, the small number of subjects, the concomitant medications allowed, and the short follow-up. Ongoing trials include new B-cell/plasma-cell targeting agents such as the Bruton tyrosine kinase inhibitors ibrutinib and rilzabrutinib, and the anti-CD38 MoAbs daratumumab and its analogue isatuximab. Further drugs in clinical trials target the complement cascade in wAIHA with complement activation, such as the C3 inhibitor pegcetacoplan and the C1q inhibitor ANX005. Finally, an interesting and non-immuno-toxic strategy is to remove the pathogenic autoantibodies via blocking the neonatal Fc receptor, by intravenous nipocalimab and subcutaneous RVT-1401. Such novel agents targeting the several immunopathological mechanisms acting in wAIHA and their possible combination, will increase the therapeutic armamentarium and possibly fill the gap of wAIHA relapsed after/refractory to rituximab. Moreover, these new target therapies may represent a tool for the unmet need of very acute cases.
摘要：
在这篇综述文章中，我们提供了对最近报告的批判性见解，这些报告评估了温暖型自身免疫性溶血性贫血（wAIHA）的创新疗法。在已发表的文章中，我们选择了使用蛋白酶体抑制剂硼替佐米联合地塞米松或利妥昔单抗的两份报告，一项关于脾酪氨酸激酶抑制剂福司他替尼的研究，和重组促红细胞生成素（rEPO）的回顾性研究。在最近的科学交流中，我们讨论了关于磷酸肌醇3-激酶δ抑制剂（PI3Kδi）parsaclisib的报告。所有研究都强调了良好的疗效，尽管有待在更大的试验中证实，并且由于WAIHA患者的异质性而存在局限性，学科数量少，允许的伴随药物，和短暂的后续行动。正在进行的试验包括新的B细胞/浆细胞靶向剂，如布鲁顿酪氨酸激酶抑制剂ibrutinib和rilzabrutinib，和抗CD38MoAbsdaratumumab及其类似物伊沙妥昔单抗。临床试验中的其他药物靶向具有补体激活的wAIHA中的补体级联，例如C3抑制剂pegcetacoplan和C1q抑制剂ANX005。最后,一种有趣且非免疫毒性的策略是通过阻断新生儿Fc受体来去除致病性自身抗体，通过静脉注射nipocalimab和皮下RVT-1401。这种新型药物靶向作用于wAIHA的几种免疫病理学机制及其可能的组合，将增加治疗性军械库，并可能填补利妥昔单抗复发/难治的WAIHA的空白。此外，这些新的靶向疗法可能是一种工具，可以满足非常急性病例的未满足需求。
