Blinatumomab plus Interfant-06 chemotherapy “appeared to be safe and had a high level of efficacy” in infants with newly diagnosed KMT2A-rearranged acute lymphoblastic leukemia (ALL), according to a recent study.
Inge van der Sluis, MD, PhD, of the Princess Maxima Center for Pediatric Oncology and colleagues conducted the research and published their findings in the New England Journal of Medicine.
“KMT2A-rearranged [ALL] in infants is an aggressive disease with three-year event-free survival below 40%,” Dr. van der Sluis and colleagues wrote. “Most relapses occur during treatment, with two-thirds occurring within one year and 90% within two years after diagnosis. Outcomes have not improved in recent decades despite intensification of chemotherapy.”
They evaluated the safety and efficacy of blinatumomab, a bispecific T-cell engager targeting CD19, in 30 patients younger than one year who had newly diagnosed KMT2A-rearranged ALL. Patients received the chemotherapy used in the Interfant-06 trial plus one postinduction course of blinatumomab. They received blinatumomab 15 μg per square meter of body surface area per day for a 28-day continuous infusion. All 30 patients received the full course of blinatumomab.
Clinically relevant toxic effects were the primary endpoint of the study and were defined by the study’s investigators as “any toxic effect that was possibly or definitely attributable to blinatumomab and resulted in permanent discontinuation of blinatumomab or death.” The researchers collected data on adverse events (AEs) and measurable residual disease (MRD). They compared outcome data with historical control data from the Interfant-06 trial.
At a median follow-up of 26.3 months, no toxic effects meeting the definition of the primary endpoint occurred. However, 10 serious AEs occurred, including four fever events, four infection events, one hypertension event, and one vomiting event. The toxic effects profile was “consistent with that reported in older patients,” according to Dr. van der Sluis and colleagues.
Nearly all (93%) patients had MRD negativity or low levels of MRD. A total of 16 patients (53%) were MRD negative and a total of 12 patients (40%) had low levels of MRD. All patients who continued chemotherapy achieved MRD negativity during further treatment. The two-year disease-free survival (DFS) rate was 81.6% and the overall survival (OS) rate was 93.3% in the current study. In the Interfant-06 trial, the two-year DFS rate was 49.4% and the two-year OS rate was 65.8%.
“Blinatumomab added to Interfant-06 chemotherapy appeared to be safe and had a high level of efficacy in infants with newly diagnosed KMT2A-rearranged ALL as compared with historical controls from the Interfant-06 trial,” Dr. van der Sluis and colleagues concluded.
van der Sluis IM, de Lorenzo P, Kotecha RS, et al. Blinatumomab added to chemotherapy in infant lymphoblastic leukemia. N Engl J Med. 2023;388(17):1572-1581. doi:10.1056/nejmoa2214171