EHA 2025 | ADVANCED: a novel conditioning regimen for alloSCT in patients with adverse-risk AML

So the sequential allogeneic stem cell transplantation usually is a two-part approach when we have the preconditioning part and the standard conditioning part but that extends to a period of usually two to three weeks so that can be actually very myelosuppressive and intensive to our patients in terms of toxicity. So that is why we’re working on in Vilnius on a novel conditioning regimen, which actually puts those two parts together in a single intensified conditioning, aiming not only as a standard conditioning prior stem cell infusion, but also to address the acute myeloid leukemia burden. So these patients, we have already 20 patients enrolled in this trial. They all have active leukemia, active acute myeloid leukemia with adverse risk features. The majority of them have TP53 mutations, complex monosomic karyotypes, MECOM rearrangements. Other patients have MDS-related mutations. These patients are, some of them are just newly diagnosed with no previous treatment exposures. Other patients are in a relapsed refractory time point. So the median blast count of the disease burden is actually 15% bone marrow blasts. So they’re all in active disease. So the conditioning regimen, the advanced conditioning regimen is structured and it uses cladribine, intermediate-dose cytarabine, venetoclax, decitabine, GCSF on days minus 9 to minus 5. So a 5-day semi-intensive approach to lower the AML burden. And then on days minus 4, minus 3, minus 2, we use the alkylating agents, such as thiotepa, busulfan, melphalan, and in some patients, TBI. So what we did see is that this approach is actually very effective for these high-risk patients, irrespective of whether these are newly diagnosed and went upfront to an upfront allo or these were relapsed refractory patients. So the complete remission rate at day 30 after the stem cell infusion was 94%. So only one patient did not respond. What we also see is that this is tolerable and in fact we had patients who were older than 70 years old successfully salvaged with this approach. The survival rates are actually too early to talk about because the follow-up is really short, it’s about five to six months. We don’t see any relapses. Treatment toxicity, we only had one early death in a patient for whom we performed this approach as a second allotransplant, so this was a difficult case, but overall the toxicity is actually tolerable, the rates of sepsis and mucositis are not something you would expect in a not higher than in a conventional approach, so of course we’re really looking forward to longer follow-up to have more patients included and to have a more broader comprehensive overview on how this approach can actually address the unmet needs for adverse risk acute myeloid leukemia patients.

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