ASH 2023 | Novel immunotherapies in AML and insights into the future of the treatment landscape

So I had the privilege to give the educational on recent developments in immunotherapy in AML, and I actually addressed all different immunotherapy platforms that are currently being employed in the setting of AML, so these are antibody-drug conjugates, fusion proteins, monoclonal antibodies, also the T-cell engagers, as well as adoptive cell therapy utilizing CAR-NK or CAR T-cells. And I’d like to highlight some recent developments which I think hold promise. 

First of all, there are novel antibody-drug conjugates targeting CD123 -pivekimab, which has really promising data in conjunction with ven/aza, so possibly novel triplets will emerge, and I think probably this will be suitable for a defined AML population. And I think on the CAR T-cell platform, there’s really interesting development of combining an engineered allogeneic stem cell graft followed by adoptive transfer of CAR T-cells or any other immunotherapy platform. And there has been some interesting data showing that CD33 knockdown stem cells are actually engrafting, and then this was followed by the application of gemtuzumab, so the CD33 drug conjugate antibody, and actually, there was no cytopenia seen. So I think modification of the stem cell graft followed by whatever immunotherapy platform is a very interesting, although in the first sight maybe complicated, approach, that is probably going to be followed now that we also have preclinical data where CRISPR-edited epitope editing of the stem cell graft, and now I’m talking about also essential proteins CD45, FLT-3, CD123 and C-kit at least preclinically have been generated, then followed by adoptive transfer of CAR T-cells. And clearly we still have to see relation to safety. So one issue is immunogenicity and also the long-term function of the stem cell graft. But this, I think, opens up an entire area in which adoptive transfer can evolve.