Standard of care for children with newly diagnosed B-cell ALL

Abstract

Adding two cycles of the immunotherapy blinatumomab to chemotherapy for children with newly diagnosed standard-risk B-cell acute lymphoblastic leukemia (ALL) improved outcomes significantly beyond any recent chemotherapy intervention according to the results of the AALL1731 trial presented at the 66th American Society of Hematology Annual Meeting and Exposition and published in The New England Journal of Medicine.^{1, 2}

At a median follow-up of 2.5 years, patients treated with blinatumomab and chemotherapy had an estimated 3-year disease-free survival (DFS) rate of 96.0% versus 87.9% for those treated with chemotherapy alone.

Among patients with an average relapse risk, the estimated 3-year DFS rate was 97.5% and 90.2% for those treated with blinatumomab plus chemotherapy and those treated with chemotherapy alone, respectively.

This is the first study to add blinatumomab to chemotherapy for patients who are newly diagnosed with National Cancer Institute (NCI) standard-risk B-cell ALL. Prior studies in both adults and children have shown the benefit of adding blinatumomab to chemotherapy for relapsed B-cell ALL.

The results are practice changing according to Elias Jabbour, MD, a professor of medicine in the Department of Leukemia at The University of Texas MD Anderson Cancer Center, who is not affiliated with the trial.

“Early integration of blinatumomab improves overall outcomes and may spare the need for intensive approaches in patients,” he says.

The AALL1731 trial, an international, phase 3, randomized controlled trial by the Children’s Oncology Group, included 1440 patients with standard-risk B-cell ALL with an average or higher risk of relapse who were randomized to chemotherapy alone (n = 722) or blinatumomab and chemotherapy (n = 718). Patients with NCI standard-risk disease were defined as those who were 1 year old or older and younger than 10 years at diagnosis and who presented with a white cell count of less than 50,000/µL.

The results are from the first interim efficacy analysis. Because of the significantly improved DFS, randomization of the trial was terminated early after the data and safety monitoring committee reviewed the results.

“The new standard, when possible, is to add two cycles of blinatumomab to the backbone of Children’s Oncology Group tested traditional therapies for patients with standard risk ALL with either an average or higher risk of relapse,” says the senior author of the study, Mignon Loh, MD, head of the Division of Pediatric Hematology, Oncology, Bone Marrow Transplant, and Cellular Therapy at Seattle Children’s Hospital.

Dr Loh says that the investigators intend to test the addition of blinatumomab in patients with high-risk ALL (older patients or those who present with higher white blood cell counts). “I feel that it is highly likely, based on available published data from us and other adult groups, that blinatumomab will also work for these patients as well.”