Clinic Conversation of the Week: How to Talk to Parents About the AALL1731 Trial in Pediatric B-ALL
Expert Perspectives · Tristan Knight, MD, FRCPC · 2024-12-10
Blinatumomab is a CD19-directed bispecific T-cell engaging (BiTE) antibody which was approved by the FDA in June 2024 for use in the management of both pediatric and adult patients with CD19-positive Philadelphia chromosome-negative B-lymphoblastic leukemia (B-ALL). Specifically, it is approved for use in the consolidation phase, for patients in either first or second remission with minimal residual disease (MRD). It is also approved for use in relapsed or refractory B-ALL.
What Is the Evidence Supporting Blinatumomab Use?
In children with relapsed/refractory disease, blinatumomab’s safety and efficacy are well-established, based on the findings in the Children’s Oncology Group (COG) AALL1331 study. In that study, children with B-ALL in first relapse were randomized to receive blinatumomab versus a third block of standard chemotherapy for consolidation treatment. Those who received blinatumomab achieved MRD-negative remission much more frequently (90% [44/49] vs 54% [26/48]; difference, 35.6% [95% CI, 15.6%-52.5%]). Additionally, serious adverse events were less frequent in the blinatumomab (24.1%) compared to consolidation chemotherapy (43.1%) group.
What Is the AALL1731 Trial?
AALL1731 is a randomized clinical trial which is investigating whether the addition of blinatumomab to standard chemotherapy will improve outcomes among children with National Cancer Institute (NCI) standard-risk B-ALL. Children enrolled on this clinical trial are randomized to receive two cycles of blinatumomab, in addition to standard multi-agent consolidation chemotherapy, or standard consolidation chemotherapy alone.
In the summer of 2024, an interim analysis identified superior outcomes among children receiving blinatumomab. As such, the COG closed the trial to accrual, halted randomization, and recommended that children who are not yet in the maintenance phase of their treatment receive blinatumomab. Understandably, this development has been a source of excitement in the pediatric oncology community, but it has also been a source of much discussion and anxiety in patient and family circles. I’ll therefore be discussing this trial as I would with the parent of a child enrolled on the study.
Here’s What I Would Say
“Some children receive cancer treatment as part of a clinical trial. When thinking about using a new drug, we do not know if adding it to the existing treatment regimen will be helpful or harmful, so it is important to test this drug before giving it to everyone. The usual way we do this is by giving some children the drug in addition to their usual therapy and comparing those to children who do not receive the drug. Whenever we do this kind of clinical trial, the group responsible for the clinical trial watches the results to see how patients are doing, even before the clinical trial is finished.
In July of 2024, this monitoring group saw that children enrolled on the COG clinical trial AALL1731 who were receiving a drug called blinatumomab were having their leukemia return or relapse much less often than children treated with standard chemotherapy alone. It is important to point out that even for the group that did not receive blinatumomab, most children did not relapse—but fewer children relapsed after receiving blinatumomab.
Based on these results, we are recommending the addition of blinatumomab to the standard chemotherapy treatment for children with standard-risk B-ALL, including those who are not enrolled on a clinical trial. When we conduct a clinical trial and see that adding a new drug to the standard chemotherapy improves outcomes, the combination of the new drug plus the standard chemotherapy becomes the new standard therapy. AALL1731 showed that blinatumomab made a big difference in outcomes, and we are therefore adding it to the standard therapy.
Blinatumomab is a drug that helps the immune system fight off B-cell leukemia by letting the body’s own immune system recognize and target cancer cells. It is administered as a continuous infusion lasting for about one month. It is typically started while inpatient but can often be given outpatient for the rest of the infusion. It has been used safely in children whose leukemia has relapsed or come back. The COG clinical trial tested whether adding two cycles of blinatumomab could be helpful for certain children with newly diagnosed B-ALL. In response to these and other results, the FDA has approved the use of blinatumomab as part of the chemotherapy regimen in patients with newly diagnosed B-ALL who are older than one month of age.
Although this data is very exciting, not every child with B-ALL should receive blinatumomab. For instance, children with B-ALL whose leukemia is classified as having favorable-risk factors already do very well with only standard chemotherapy. Blinatumomab has not been tested in children with this kind of disease, and we do not know whether risks versus benefits warrant its use. Additionally, blinatumomab has not been studied during all phases of treatment.
Right now, we only know that adding blinatumomab to the consolidation phase of chemotherapy (the second block of therapy) helps children. We don’t know what would happen, if anything, if we added it to maintenance chemotherapy. We are therefore not planning to give blinatumomab to children who are already in the maintenance phase of their treatment. However, if a child did not receive blinatumomab and is not yet in maintenance but has completed consolidation, that child will receive additional cycles with blinatumomab to make up the doses that were not given.”
About Dr. Knight
Tristan E. Knight, MD, FRCPC, is a Clinical Assistant Professor of Pediatrics at the University of Washington (Seattle, WA) and practices at Seattle Children’s Hospital. He completed his Pediatric Residency at the University of Hawaii, a Pediatric Hematology/Oncology Fellowship at the Children’s Hospital of Michigan, and a Bone Marrow Transplant (BMT)/Cellular Therapy Fellowship at the Hospital for Sick Children (SickKids). His clinical areas of interest are allogeneic/autologous BMT and cellular/immune effector cell therapy, particularly in the treatment of children with ALL, AML, and neuroblastoma. He has published extensively on novel therapeutic approaches in these conditions, including the use of CAR T-cell therapy in children.