ASH 2022 | ASH 2022 LBA: results from the ECOG-ACRIN E1910 trial

So patients, adult patients with acute lymphoblastic leukemia typically have a poor prognosis because they tend to have more resistant leukemia. And because of side effects from treatment, they can oftentimes have severe complications. It can even lead to their death. So their outcomes are not very good. There’s a concept now of minimal residual disease, or measurable residual disease we call it, where we can assess patient’s response to treatment. And if they are in a remission by our conventional criteria but they have small amounts of leukemia in their bone marrow, we know that they’re more likely to relapse as they continue their treatment. So there’s a number of immunologic agents that have been utilized now in recent years that have shown benefit in patients where the leukemia has come back.

And in particular, there’s an agent called blinatumomab. Blinatumomab is what’s called a bispecific T cell engager molecule. It brings a T cell close to a leukemia blast cell and kills it. This is approved in the United States by the Food and Drug Administration for patients with relapsed/refractory disease where the leukemia has come back or hasn’t responded to treatment and also patients that have this MRD or measurable residual disease-positive state where we know they have a high risk of relapse. However, we know that patients that get into remission and are still MRD-negative, so they seem to have a better prognosis, but we know that they can still relapse down the road.

So in this E1910 clinical trial that we conducted in the United States through the National Clinical Trials Network, we aimed to see if adding blinatumomab to chemotherapy in patients who were MRD-negative could lessen their risk of leukemia coming back. Patients underwent two months of induction chemotherapy, then they got some additional chemotherapy to prevent the leukemia from showing up in their central nervous system. And then at that point, we assess their measurable residual disease status. And if they were MRD-negative, then we randomized them to continue more chemotherapy that we call consolidation chemotherapy, or to give them four cycles of blinatumomab plus the four cycles of chemotherapy. And then they went on to maintenance therapy. Blinatumomab is given by a continuous IV infusion for four weeks. So there were four cycles of that interspersed through their treatment.

And what we showed was the patients that got the blinatumomab compared to the patients that got the conventional chemotherapy did much better. Their overall survival of three and a half years was 83% compared to 65% for the patients who received the chemotherapy only. And this mainly was because we prevented their leukemia from coming back. So those patients that got the blinatumomab plus chemotherapy relapsed less. So we’re very encouraged by these results. We think it’s a new standard of care, and that it’s something that needs to be considered in the management of these patients going forward.