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Adding a postinduction course of blinatumomab (Blincyto) to chemotherapy appeared safe and highly effective for treating an aggressive form of acute lymphoblastic leukemia (ALL) in infants, according to results from a

Of the 30 infants with newly diagnosed KMT2A-rearranged ALL, 16 achieved minimal residual disease (MRD)-negative status following the 28-day infusion with blinatumomab and an additional 12 patients had low MRD levels (<5×10^-4), reported Inge M. van der Sluis, MD, PhD, of the Princess Máxima Center for Pediatric Oncology in Utrecht, the Netherlands, and colleagues.

The regimen, which combined the anti-CD19 bispecific T-cell engager blinatumomab with the Interfant-06 chemotherapy backbone, appeared safe, with toxic effects "consistent with that reported in older patients," the researchers wrote in the .

At 2 years, disease-free survival (DFS) and overall survival (OS) rates were 81.6% (95% CI 60.8-92.0) and 93.3% (95% CI 75.9-98.3), respectively.

"These outcome data are very promising, given the poor survival and lack of improvements in outcomes among infants with KMT2A-rearranged ALL in recent decades," van der Sluis and co-authors wrote, adding that while longer follow-up is pending, "the low incidence of relapse after treatment with blinatumomab is remarkable, given that in historical controls relapses occur frequently and early during therapy."

They noted that the DFS and OS rates in the current study were both substantially higher than in similar patients treated with the chemotherapy protocol alone in the original (49.4% and 65.8%, respectively), with those differences resulting in corresponding hazard ratios of 0.22 (95% CI 0.09-0.34) for DFS and 0.15 (95% CI 0.04-0.62) for OS.

The results are "really remarkable," agreed Elizabeth Raetz, MD, of Hassenfeld Children's Hospital at NYU Langone in New York City, who was not involved in the study.

"Historically, it's been very challenging to treat infants with ALL, and their disease-free survival, overall survival rates have been much lower than what you see in older children" Raetz told MedPage Today. "So this is really one of the first trials that's demonstrated a very significant improvement in their outcomes."

Historically Poor Outcomes

The researchers noted that while outcomes among older children with ALL have improved over the years, infants with ALL diagnosed in their first year have a poor prognosis. Infants with KMT2A-rearranged ALL, which is found in 75% of babies with ALL, have the worst outcomes, with a 6-year event-free survival of only 36% in Interfant-06, which was conducted from 2006 to 2016, the team said.

Furthermore, the investigators pointed out that in that trial, 90% of relapses occurred during the first 2 years of treatment, with two-thirds occurring within the first year, "which illustrates the aggressiveness of this specific type of ALL."

The researchers explained that since blinatumomab has been shown to be safe and effective in older children and adults with relapsed or refractory B-lineage ALL after intensive chemotherapy, the team hypothesized that a course of blinatumomab could be safely added to the Interfant-06 backbone regimen and improve outcomes in infants with KMT2A-rearranged ALL.

The 30 infants were enrolled from July 2018 through July 2021 at 12 sites in nine countries. Nine patients were considered to be high risk (defined as being less than 6 months at diagnosis with a white-cell count of at least 300×10⁹/L at diagnosis or a poor response to prednisone), while the remainder were classified as medium risk. (There were no significant differences between these patients and the selected Interfant-06 historical controls.)

After a month of induction therapy, patients received one cycle of blinatumomab, after which they were treated in accordance with the Interfant-06 protocol, with consecutive courses of protocol IB (cyclophosphamide, cytarabine, and mercaptopurine); MARMA (high-dose cytarabine, high-dose methotrexate, mercaptopurine, and asparaginase); OCTADAD (vincristine, dexamethasone, asparaginase, daunorubicin, thioguanine, cytarabine, and cyclophosphamide); and maintenance therapy (mercaptopurine and methotrexate).

All patients with an MRD of at least 5×10^-4 before OCTADAD were candidates for hematopoietic stem cell transplantation (HSCT) in the first complete remission. HSCT was performed in eight of nine high-risk patients, while none of the 21 medium-risk patients received HSCT because of persistent high levels of MRD.

Ten serious adverse events (AEs) were reported, including fever, infection, hypertension, and vomiting. No fatal AEs were reported, and no patients had neurologic events. The most frequent grade 3 or higher AEs were anemia in 17%; and febrile neutropenia, neutropenia, and elevated γ-glutamyltransferase levels in 7% each. The most frequent low-grade AEs were hypertension, vomiting, and diarrhea, each occurring in 13% of patients.

One death during first remission occurred just before HSCT (considered to be unrelated to blinatumomab).

There were four relapses, the researchers reported. Two medium-risk patients had a combined bone marrow-central nervous system (CNS) relapse during maintenance treatment and as of the time of publication of the study are in continuous second complete remission. Another medium-risk patient had a CNS relapse during protocol IB and is in second complete remission after MARMA and HSCT, while a fourth relapse occurred in a high-risk patient who had a combined bone marrow-CNS relapse 2 months after HSCT.

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