Prof Rachel Rau (University of Washington, Seattle Children’s Hospital, Seattle, WA, USA) joins touchHAEMATOLOGY to discuss the findings from the phase 3 AALL1731 study, a plenary session presented at the 66th ASH Annual Meeting & Exposition. This pivotal trial evaluated blinatumomab, an innovative immunotherapy, in children with NCI standard risk B-cell acute lymphoblastic leukemia (B-ALL). Results revealed a significant improvement in 3-year disease-free survival, reducing relapse rates by 61% compared to standard chemotherapy alone. While blinatumomab was well tolerated overall, the study also highlighted an increased risk of infections in some patient groups. These findings position blinatumomab as a new treatment standard for most pediatric B-ALL patients, marking a potential new standard of care in leukemia therapy.
The session, ‘Blinatumomab Added to Chemotherapy Improves Disease-Free Survival in Newly Diagnosed NCI Standard Risk Pediatric B-Acute Lymphoblastic Leukemia: Results from the Randomized Children’s Oncology Group Study AALL1731’. Abstract 207450 was presented at the 66th ASH Annual Meeting & Exposition on 7–10 December 2024 in San Diego, CA, USA.
Disclosures: Prof Rau is a consultant for Jazz, a member of the Advisory Board for Jazz and Servier and has received honoraria/honorarium from Jazz.
Transcript
I’m Rachel Rau. I’m a pediatric oncologist at Seattle Children’s Hospital in Seattle, Washington.
So, the trial that I discussed at ASH this year was a children’s oncology group run phase 3 trial called AALL1731. This trial, enrolled children with NCI standard risk b-cell acute lymphoblastic leukemia, and that is defined as children who are between the ages of 1 and 10 years of age when they’re diagnosed and have a presenting white blood cell count of less than 50,000 at the time of diagnosis. This makes up about two-thirds of all pediatric B-ALL cases, so it’s, you know, our most common subset of patients.
These patients were enrolled on trial, and once they started therapy with our 3-drug induction at the end of that, then they were assigned to one of three groups based on their expected risk of relapse. Patients with really favourable expected prognosis, with standard chemotherapy alone were called our ‘standard risk favourable’ group. And that group, since they do so well with our standard chemotherapy, they were non-randomly assigned to just standard therapy. The other two groups, had either an intermediate risk of relapse called ‘standard risk average’, and then our higher risk of relapse patients were grouped into a subset called ‘standard risk high’. And it was a standard risk average and standard risk high patients who were eligible for the randomization on this trial. And that randomization included either, a standard risk adapted chemotherapy backbone or that same chemotherapy backbone plus two 28-day cycles of continuously infused blinatumomab.
And blinatumomab is an immunotherapy, which, one end of the molecule binds to CD19 on the surface of the ALL lymphoblasts, and the other side binds to CD3 expressing T-cells. So it engages the patient’s normal T-cells to attack and eliminate the malignant b-cells. So it works in a very different way than most traditional chemotherapies. And, essentially, what we found is amongst patients on our trial who are randomized to receive blinatumomab , the 3-year disease free survival was 96% percent compared to 87.9% for those patients randomized to receive their standard chemotherapy alone, so a significant improvement. That gave a hazard ratio of 0.39, which equates to a 61% reduction in events. And that improved disease free survival was secondary to a significant reduction in relapses. We saw dramatically reduced incidence of relapse in the overall cohort. And if we just look separately at the standard risk average and standard risk high patients, all of them had a significant reduction in relapses.
Importantly, while it reduced the rates of bone marrow involving relapses, the more rare event of an isolated central nervous system relapse was not impacted by the addition of blinatumomab. And that finding actually wasn’t surprising since we know blinatumomab doesn’t have great CNS directed activity. So still sort of future directions for research would be to come up with new ways to address that risk as well.
Overall in the trial, blinatumomab was well tolerated. There were no deaths during blinatumomab therapy, and there were no deaths deemed attributable to blinatumomab in any of our randomized patients. And we had really close infectious disease monitoring in the course of 1731, and we didn’t see differences in the rates of infectious complications in our standard risk high group. But in our standard risk average group, we did note that there was an increased risk of grade 3+ sepsis and catheter-related infections among those who are randomized to receive blinatumomab. And some of that was due to the incidence of infections during blinatumomab cycles themselves, but most of it was actually due to increased rates of those infectious complications in the chemotherapy courses that followed blinatumomab, extending to and even a bit beyond a year after completion of all blinatumomab therapy. So we need to delve into the reasons for that increased risk of infection. We think it might be due to ablation of normal b cells in the patients who receive blinatumomab.
So, you know, we’re we’re working to to dig through those data that we did collect in the context of this trial, but we don’t yet have the answers quite yet. Fortunately, if we just isolated our evaluation to those with severe grade 4 or fatal grade 5 infectious complications, those were super rare on the overall trial and did not differ between arms. So it’s really you know, it’s not great that they had infections, but it’s good to know that they weren’t, you know, of a more severe nature, in the face of blinatumomab therapy.
So what does this mean overall? Number 1, our trial really demonstrates that for patients with NCI standard risk B-ALL of average or higher risk of relapse, blinatumomab added to chemotherapy is really a new treatment standard for that group of patients. And more broadly speaking, if we sort of take a few steps back and look at the published literature just over the past couple of years, we now know for newly diagnosed patients with B-ALL, the addition of blinatumomab to chemotherapy benefits infants, adults and now patients with NCI standard risk disease.
The one sort of gap in the groups that we’ve studied are patients with NCI high-risk B-ALL. So that’s a group really enriched for adolescent patients, but very reasonable to extrapolate from our standard risk high patients and the young adults treated on the recent ECOG-ACRIN study because their treatment approach and their expected outcomes are quite similar to the NCI high-risk population. So, overall, for a vast majority of newly diagnosed B-ALL patients, blinatumomab is should now be considered a standard component of therapy.
This content has been developed independently by Touch Medical Media for touchHAEMATOLOGY. It is not affiliated with the American Society of Hematology (ASH). Unapproved products or unapproved uses of approved products may be discussed by the faculty; these situations may reflect the approval status in one or more jurisdictions. No endorsement of unapproved products or unapproved uses is either made or implied by mention of these products or uses by Touch Medical Media or any sponsor. Views expressed are the speaker’s own and do not necessarily reflect the views of Touch Medical Media.
Interviewer/Editor: Sophie Nickelson
Cite: Rau R. Blinatumomab advances outcomes in paediatric B-ALL: phase 3 AALL1731 trial findings. touchHAEMATOLOGY. 19 December 2024.
