Infants with KMT2A-rearranged acute lymphoblastic leukaemia (ALL) – a dire disease with poor prognosis despite treatment intensification under the latest protocols – are found to have improved 4-year disease-free survival (DFS) and overall survival (OS) with the addition of blinatumomab to standard chemotherapy.

In a phase II single-arm interventional study conducted between July 2018 and July 2021 across nine countries in Europe and in Australia, 30 infants with KMT2A-rearranged ALL received one cycle of blinatumomab (28-day continuous infusion at 15 μg/m²/day) added postinduction to the standard Interfant-06 chemotherapy protocol. DFS and OS rates at 4 years were compared with selected historical controls from an Interfant-06 cohort. [Martins MV, et al, EHA 2026, abstract PS1490]

Additionally, serum immunoglobulin G (IgG) levels were monitored systematically from the start of the blinatumomab cycle through to the start of protocol IB in the Interfant-06 backbone, with subsequent measurements performed at investigators’ discretion, to delineate patterns of IgG depletion and recovery following blinatumomab treatment.

Increased 4-year DFS & OS

“Adding blinatumomab to upfront standard therapy resulted in a sustained beneficial outcome for infants with KMT2A-rearranged ALL,” the investigators reported.

At 4 years, DFS rate was 83.3 percent for blinatumomab-treated infants compared with 44 percent in Interfant-06–selected historical controls, while 4-year OS rate was 93.3 vs 60.2 percent.

Patterns of IgG depletion & recovery

A total of 169 IgG values were documented. These showed a steady decrease over the course of blinatumomab treatment, dropping from a median of 2.82 g/L (Z-score, -0.72) on day 1 and 3.35 g/L (Z-score, -0.67) on day 2 of blinatumomab to a median nadir of 2.05 g/L (Z-score, -1.29) at the start of the next treatment phase (ie, protocol IB). Subsequently, IgG levels gradually normalized (>4 g/L). All available IgG values normalized by the last 3 months of the maintenance phase.

“The delay in IgG recovery suggests a combined cumulative effect with blinatumomab and subsequent chemotherapy. Continued monitoring is required,” the investigators noted.

Nearly two-thirds (63 percent) of patients received intravenous Ig (IVIg) supplementation, which was given predominantly (40 percent) during the blinatumomab cycle.

Safety profile

Although blinatumomab impairs IgG production, infections during blinatumomab treatment remained minimal as compared with other treatment phases, accounting for 8 percent of all infections reported during the protocol.

Notably, no postinduction infectious deaths occurred among blinatumomab-treated patients. Among Interfant-06–selected historical controls, the rate of postinduction infectious deaths was 4 percent.

Clinical implications & future directions

“While adding blinatumomab to upfront therapy consistently led to a decrease in Ig levels, we identified a shorter nadir and earlier recovery of IgG in infants compared with adults, where limited evidence points to a late recovery with a nadir around 57 weeks after blinatumomab treatment,” the investigators noted.

“Our findings can guide pre-emptive strategies for IVIg replacement to prevent significant treatment-related hypogammaglobulinaemia,” they continued. “As Ig levels vary widely in infants, decisions on IVIg supplementation should be guided by infant age-specific reference ranges. A more conservative supplementation approach is supported unless clinically relevant infections are observed.”

“Ongoing trials of blinatumomab should involve systematic monitoring of Ig recovery throughout treatment to further refine infection prevention strategies and validate the improved survival outcomes reported in our study,” they added.

Blinatumomab improves 4-year survival in infants with KMT2A-rearranged ALL