ASH 2023 | Uproleselan added to cladribine + LDAC for treated secondary AML: insights from a Phase Ib/II study

So at this year’s ASH meeting 2023, we presented our data with uproleselan combined with our backbone of cladribine and low-dose cytarabine in patients with newly diagnosed treated secondary AML. So before I go on, I want to remind you all that treated secondary AML is a term given to those patients who had prior MDS who received therapy for their MDS with hypomethylating agents and then developed acute myeloid leukemia, so-called ts-AML. They were previously called hypomethylating agent failure, who then develop AML. But this is a specific subgroup of patients, which in fact was excluded from the VLA study and are very difficult population of patients to treat, with a median survival of 4 to 5 months and a very low response rate and high rates of early mortality.

So we decided to use uproleselan, which is an agent that targets e-selectin, which can be upregulated after hypomethylating agent-exposure, hence the rationale to combine this with chemotherapy. So we’ve treated 20 patients thus far, 18 evaluable, with a median age of 72. These were people who had received prior HMA but also prior HMA-Ven for their myelodysplastic syndrome. And what we found is that the overall response rate was around 50%, including 11% CRi, 6% CRp and 22% MLFS. A good proportion of these patients were able to move to allogeneic stem cell transplantation. And we are now correlating the expression of e-selectin with responses in this patient population. Notably, the early mortality rate was relatively low for this population with this low intensity regimen that does not include high-intensity chemotherapy nor anthracyclines. And so this may be a good regimen going forward in this very difficult population.