ASH 2025 | ARCHIVE conditioning for upfront alloSCT in active AML and high-risk MDS-IB2

We know that poor risk, acute myeloid leukemia, as well as relapsed refractory setting, all require an allograft for a curative, consolidative approach. However, due to the lack of efficacy of remission induction therapies, or in some cases, the excessive toxicity, a proportion of patients become ineligible for an allograft. So we’re performing our single center study of an upfront allogeneic stem cell transplant approach using an investigative conditioning regimen of alkylating agents, cytarabine, cladribine, hypomethylating agents, and venetoclax, which is called ARCHIVE, and we use it for upfront allografting in patients with active acute myeloid leukemia, so no remission induction. These can be either newly diagnosed patients or relapsed refractory patients, and also patients with MDS-IB2 were also enrolled. Importantly, we have enrolled 25 patients of whom 16 were female. The majority, 80%, had acute myeloid leukemia and the remaining 20% had MDS-IB2. So the median age of this cohort was 57 years. 18 patients had an ECOG of zero or one. So that’s 72% and the remaining 28% had an ECOG of two. So importantly, the majority also had relapsed refractory disease, that would be 84%, where the remaining four patients had been newly diagnosed. Unsurprisingly, the vast majority of patients, 80%, had a poor risk by ELN 2022 risk stratification. As for relapsed refractory patients, the median number of prior therapy lines was one. However, there were patients who were heavily pre-treated with up to eight prior therapy lines. Importantly, in the relapsed refractory subgroup, more than half of the patients, 52%, were exposed previously to venetoclax, 12% to FLT3 inhibitors, and 8% to venetoclax, and 4% to BCR-ABL inhibitors. So different targeted therapies were already used in these patients. Importantly, for 28%, this approach was actually not the first allograft. So seven patients had already relapsed after the first, second, or even third transplant. Regarding the median blast count at baseline prior to the initiation of this investigative conditioning regimen, so the median blast count was 13%, so all patients had active leukemia while starting their conditioning. Importantly, all patients had been allografted after this conditioning regimen. Different donors were used for stem cell collection, so 56% were transplanted from a haploidentical donor. So more than half of the patients had received a haploidentical transplant. 28% had a matched unrelated donor and 8% had been transplanted from a mismatched unrelated donor and the remaining 8% from a matched sibling donor, so different donors, of whom more than half were haploidentical. So what have we achieved with this conditioning regimen in this approach is that the complete remission rate plus complete remission with incomplete platelet recovery rate at day 30 post-transplant was 96%, so almost all patients, 23 out of 24, had achieved a complete remission. Importantly, almost all patients, 23 out of 24, had achieved a complete remission. Importantly, almost all available patients were MRD negative by multiparametric flow cytometry at a 91% MRD negativity rate. So two patients did not achieve MRD negativity at day 30 post-transplant. Importantly, the neutrophil and platelet recovery times were actually similar to the ones you would expect in patients proceeding to an allograft. So the median time to neutrophil recovery was 16 days, and for platelet recovery, that was 25 days, taking into account that the majority of patients had received PTCL as their T-cell depletion. Unsurprisingly, grade 3, 4, 5 infectious complications were common and were confirmed in 88% of cases. So almost all patients had an infectious complication, but again, this is not something unexpected in these patients. The D30 mortality was 8%. Right now at the data cutoff, 20 patients are alive and in CR with no confirmed relapses at the data cutoff. There were five deaths due to infectious complications or GvHD. So the median follow-up time was short, it was five months, and right now the median OS and relapse-free survival rates, median rates were not reached. Overall, we do see that the early results are very promising of this approach of this investigational conditioning regimen, which is used for an upfront allograft, allowing patients to achieve a CR at a very high rate and also omitting the standard induction chemotherapy or venetoclax and HMA-based therapy.

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