With Chemo, Blinatumomab Boosts DFS in Pediatric B-ALL

SAN DIEGO — The addition of the bispecific T-cell engager blinatumomab (Blincyto) to chemotherapy greatly boosted 3-year disease-free survival (DFS) in younger pediatric patients with newly diagnosed, standard-risk B-cell acute lymphoblastic leukemia (B-ALL), in a phase 3 randomized trial. 

Among pediatric patients with B-ALL followed for a mean of 2.5 years (1.6-3.2 years), 718 patients in the blinatumomab-plus-chemotherapy group had a 3-year DFS of 96.0±1.2% compared with 87.9±2.1% of the 722 patients in the chemotherapy-only group, researchers reported here at the American Society of Hematology (ASH) 2024 Annual Meeting.

“Our results demonstrate that blinatumomab added to chemotherapy represents a new treatment standard for most patients with NCI [National Cancer Institute] standard-risk [B-ALL],” said first author Rachel E. Rau, MD, Seattle Children’s Hospital, University of Washington, during a news briefing.

As Cynthia E. Dunbar, MD, chief of the Translational Stem Cell Biology Branch at the National Heart, Lung, and Blood Institute, noted in a news briefing: “B-cell ALL is the most common childhood cancer and one of the most treatable. However, some children still relapse following standard chemotherapy treatments and then have a much grimmer outcome.”

The AALL1731 study was initiated in 2019 with a recruitment goal of 2245 participants. The patients were over age 1 and less than 10 years, with an initial white blood cell count of

The control group received standard-intensity chemotherapy (standard risk–average patients) or augmented Berlin-Frankfurt-Münster (BFM)-based chemotherapy (standard risk–High patients). In addition, the blinatumomab groups received 2 cycles of the drug. 

Randomization was terminated in 2024 at 1440 patients because of the positive results. Patients had a median age of 4.3 years (2.8-6.4), 52.6% were boys, 26% were Hispanic, and 5% were non-Hispanic Black. 

The addition of blinatumomab improved DFS by 61% (hazard ratio, 0.39; 95% CI, 0.24 – 0.64; P

In the group of standard risk–average patients, 3-year DFS was 97.5±1.3% in the blinatumomab group versus 90.2±2.3% in the control group (HR, 0.33; 95% CI, 0.15 – 0.69). For standard risk–high patients, 3-year DFS was 94.1±2.5% and 84.8±3.8%, respectively. 

Six deaths occurred in remission, all in standard risk–high patients and none during blinatumomab cycles. Out of first courses of blinatumomab, 0.3% were associated with Grade 3 or higher cytokine release syndrome and 0.7% with seizures.

“We did note higher rates of subsequent sepsis and catheter-related infections in our standard risk–average patients who received blinatumomab,” Rau said. 

“The improvement in disease survival was secondary to significant reduction in bone marrow relapse,” Rau added. “We did not see a similar reduction in the more rare event of an isolated central nervous system relapse. This finding was not surprising given blinatumomab’s known limited activity in the central nervous system.”

Rau noted that there are two challenges in terms of access to blinatumomab: its cost, at about $225,000 per a 2023 report, and its administration. The drug is administered via 4-week–long infusions. “The delivery method is very cumbersome,” she said. 

“These are big problems that are going to take the combined efforts of pediatric oncologist cancer consortia and pharmaceutical industry partners as well as government agencies,” she said. Fortunately, she said, in June 2024 the US Food and Drug Administration approved blinatumomab for adult and pediatric patients 1 month and older with CD19-positive Philadelphia chromosome-negative B-ALL in the consolidation phase of multiphase chemotherapy. 

“So it’s relatively easy, at least, to prescribe blinatumomab in the United States for our patients that we feel would benefit from it,” she said. 

As for method of delivery, Rau said easier-to-deliver formulations are in development. 

Rau has disclosed spousal employment (AbbVie), serving on advisory boards (Servier, Jazz), consulting, and receiving honoraria (Jazz). Other study authors report various disclosures including ties with Amgen, the maker of blinatumomab. Dunbar has reported no relevant financial relationships. 

Randy Dotinga is an independent writer and board member of the Association of Health Care Journalists.