A phase II study has found that adding a postinduction course of blinatumomab (Blincyto) to chemotherapy is safe and highly effective for treating an aggressive form of acute lymphoblastic leukemia (ALL) in infants. The study, conducted by researchers from the Princess Máxima Center for Pediatric Oncology in Utrecht, the Netherlands, found that 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.”
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). At 2 years, disease-free survival (DFS) and overall survival (OS) rates were 81.6% and 93.3%, respectively. These outcomes are very promising, given the poor survival and lack of improvements in outcomes among infants with KMT2A-rearranged ALL in recent decades.
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 Interfant-06 trial. Historically, 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 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. 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 study found the addition of blinatumomab to chemotherapy to be safe and highly effective for treating aggressive ALL in infants, with promising outcomes for DFS and OS rates. Longer follow-up is pending, but the low incidence of relapse after treatment with blinatumomab is remarkable, given that in historical controls relapses occur frequently and early during therapy.
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