New directions in aplastic anemia and PNH

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Presentation ID p414-1


Presenter: Cansu Koyunlar, Rotterdam, Netherlands

The study authors conclude that their results indicate a reduced functionality of aged and transplanted Gata2+/− HSCs in multiple lineages. Currently, they are working on the identification of Gata2 haploinsufficiency phenotype and the analysis of transcriptomic changes in Gata2 haploinsufficient HSCs observed in our aged Gata2+/− mouse model. Additionally, they are working on understanding the clonality of HSCs in the aged Gata2+/− mice.


The study authors show that HLA-DR-lacking HSPCs were exclusively detected in AA/PNH patients with DR15. This suggests that CD4+ T cells specific to autoantigens presented by DR15 are involved in the development of bone marrow failure. According to the study authors, the presence of hematopoietic stem progenitor cells (HSPCs) partially lacking DR in these patients suggests the presence of HSPCs that lack DR15 but retain the other DR allele. And: given that DR(-) cells were only detected in GPI(+) HSPCs and the expansion of DR(-) cells occurred concomitantly with the expansion of GPI(-) clones after CsA cessation, the antigen-specific CD4+ T-cell attack against HSPCs is likely responsible for the survival advantage of GPI(-) HSPCs in AA/PNH.


The study authors conclude that data from the SOAR study indicate that ETB + CsA therapy may be beneficial as a first-line treatment for severe aplastic anemia patients who cannot use anti-thymocyte globulin. The authors mention the particularly notable ORR, given the median age of this patient cohort (55.0 years). No new safety signals were identified.


The study authors show that Iptacopan is a new, well-tolerated oral factor B inhibitor that blocks both intra- and extravascular hemolysis in patients with hemolytic paroxysmal nocturnal hemoglobinuria (PNH). The 12-week study results demonstrate that, in anti-C5 naive patients with active hemolysis, iptacopan therapy ≥50 mg BID results in normalization of various hemolytic markers and resolution of anemia. Maximal effects on various efficacy parameters were obtained at 200 mg BID. According to the study authors, these results demonstrate that proximal inhibition of the complement cascade parallel and further improves the hematological benefit seen with anti-C5 therapies, with iptacopan eventually offering an alternative first-line therapy for patients with PNH.


The study authors show that adult patients with paroxysmal nocturnal hemoglobinuria (PNH) with suboptimal response on prior ECU treatment received pegcetacoplan in this continuation of the PEGASUS trial and experienced durable treatment effect in all efficacy parameters at Week 48. The safety profile of pegcetacoplan was consistent with previously reported data. The results suggest that pegcetacoplan represents a new effective therapeutic option for patients with PNH.