EHA 2025 | The effectiveness of sequential alloSCT in patients with venetoclax-exposed R/R AML or MDS-IB2

First of all, the patients who had been previously treated with venetoclax and have relapsed or refractory to that therapy is really one of the highest unmet needs in acute myeloid leukemia and MDS-IB2. So what we have been doing in Vilnius is actually offering these very poor prognosis patients a sequential allogeneic stem cell transplantation as a salvage treatment. So we don’t try to induce a remission and then go in a conventional manner to an allotransplant, but we just go an upfront allogeneic approach. We had 25 patients who had previously been exposed to venetoclax regimens, so half of those patients were actually treated with Ven-HMA as a frontline regimen and relapsed or were refractory to it. The other half of the patients had actually been unsuccessfully treated with venetoclax salvage regimens. That could be venetoclax plus chemo or the same venetoclax plus HMA. So these 25 patients went on to a sequential allotransplantation, which was a double, a two-part treatment, which consisted of a 10-day venetoclax, also venetoclax-based conditioning, preconditioning, I would call it, with low-dose chemotherapy, such as, cytarabine, cladribine, also adding decitabine to it. So it’s a four or five drug combination, which aims to have a lower toxicity, but also to lower the disease burden. So after those 10 days, the patients went on to standard conventional conditioning with alkylating agents such as busulfan, melphalan, thiotepa. So after that, the patients went to the stem cell infusion. And then, of course, standard post-transplant care, such as post-transplant cyclophosphamide for GvHD prophylaxis. And the majority of patients actually had received stem cells from haploidentical donors. So 60% of patients were actually transplanted from a haploidentical donor and the remaining 40 had actually been transplanted with matched unrelated or matched sibling donor stem cells. So at day 30 after the stem cell transplantation, so the first disease evaluation, it actually showed that the response rates to this regimen is 95%. Almost all patients were in complete remissions. Importantly, what we actually also saw that the MRD negativity rate was also high, so 86% of responders had an MRD negativity at day 30. These high response rates were of course encouraging, however, we did see some treatment-related mortalities especially in elderly patients, so the median age was 56 years old, but some patients were older than 65 in their 70s and this was a toxic regimen to them so three patients unfortunately had died due to treatment toxicity within the first 30 days. The median overall survival for all patients was 10.5 months and the median relapse-free survival was 9.6 months. So what we actually show here that even those patients who are in the majority of cases are deemed to be treated in a palliative intent. We try to salvage them and I think we’re very happy that some patients are still in prolonged CRs and doing well after this approach.

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