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SOHO 2025 | Novel concepts in TP53-mutated MDS: from p53 reactivators to immune-based therapies
In this video, David Sallman, MD, Moffitt Cancer Center, Tampa, FL, highlights promising concepts being explored for the treatment of TP53-mutated myelodysplastic syndromes (MDS). He emphasizes the need for novel approaches that do not rely on standard cytotoxic chemotherapy and notes some novel agents being explored, including rezatapopt, pivekimab sunirine, and tagraxofusp. This interview took place at the 13th Annual Meeting of the Society of Hematologic Oncology (SOHO 2025) in Houston, TX.
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Transcript
Yeah so I think this has been a big challenge. We’ve had, you know, several pivotal concepts, both the magrolimab concept that I mentioned, as well as earlier experience with Eprenetapopt or APR-246 that unfortunately have failed. So what is promising? There is one other p53 reactivator. This is specific for the Y220C variant. So there is an agent called that has presented data several times in solid tumors, but we do have a first-in-human trial led by Courtney DiNardo at MD Anderson, hopefully will be a part of in the future as well...
Yeah so I think this has been a big challenge. We’ve had, you know, several pivotal concepts, both the magrolimab concept that I mentioned, as well as earlier experience with Eprenetapopt or APR-246 that unfortunately have failed. So what is promising? There is one other p53 reactivator. This is specific for the Y220C variant. So there is an agent called that has presented data several times in solid tumors, but we do have a first-in-human trial led by Courtney DiNardo at MD Anderson, hopefully will be a part of in the future as well. So I think those patients, again, it’s probably 1%, but that could be one, I think, exciting agent looking also in combination with azacitidine. I think the key question is just novel concepts. So for example, azacitidine venetoclax pivekimab, which we presented several times, It should have updated data at ASH. We have seen nice responses. Again, response is probably not enough, but looking at durability, I would say my experience has been that this is better than standard of care. And I think that is an interesting agent. Pivekimab potentially also tagraxofusp, also looking potentially in that space as well. So again, novel concepts that don’t rely on standard cytotoxic chemotherapy. I think any immune-based strategy that we could incorporate even in frontline makes sense. So Cusatuzumab, which is an anti-CD70 therapy, has a randomized Phase II trial ongoing that’s biased a little bit towards treating the adverse risk in p53 mutant. And a couple of other agents tuspetinib with a little bit of data, maybe even actimab. Again, nothing that I would say is clearly a home run, but the strong argument is that we do at least have trials. and I think data will speak for itself, ideally focusing more on molecular eradication and the durability of response more than just sort of a composite CR/CRh.
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Disclosures
Consultancy: AbbVie, Agios, Debiopharm, Janssen, Johnson & Johnson, Molecular Partners, Novartis
Advisory Board: AbbVie, Agios, Astellas, AvenCell, Bristol-Myers Squibb, BlueBird Bio, Dark Blue Therapeutics, Geron, Novartis, Shattuck Labs, Servier, Syndax, Syros, Taiho Oncology
Research Funding: Aprea, Jazz
