Blinatumomab Plus Chemo Show Improved Survival in Infants with KMT2A-r ALL

Findings from a long-term follow-up study on the use of blinatumomab (Blincyto) in infants with KMT2A-rearranged acute lymphoblastic leukemia (KMT2A-r ALL) demonstrate that adding a single post-induction course of blinatumomab to standard Interfant-06 (NCT00550992) chemotherapy results in a striking and durable improvement in survival.¹

With a median follow-up of 4.2 years, patients receiving blinatumomab achieved a 4-year disease-free survival (DFS) of 83.3% and overall survival (OS) of 93.3%. These outcomes are a dramatic improvement over a historical control cohort, which had a 4-year DFS of 44.0% and OS of 60.2%.

The addition of blinatumomab led to a significant and sustained improvement in survival outcomes. The benefit was maintained over the long-term follow-up period, with no new events (relapse, death, or second malignancy) reported since the initial publication, which had a median follow-up of 2.2 years. This is particularly noteworthy as it extends beyond the 2-year window where relapses historically occur.

In the blinatumomab study group, DFS was 83.3% (95% CI, 64.5%-92.7%) vs 44.0% (95% CI, 37.0%-50.8%) in the Interfant-06 control group. OS was 93.3% (95% CI, 75.9%-98.3%) in the blinatumomab group vs 60.2% (95% CI, 53.0%-66.7%) in the control group. The cumulative incidence of relapse was 13.3% (95% CI, 4.1%-28.1%) in the blinatumomab group vs 49.6% (95% CI, 42.5%-56.3%) in the control group.

Toxicity and Safety Profile

The combination of intensive chemotherapy and blinatumomab-induced B-cell aplasia creates a state of prolonged immunosuppression. While infections were common, the toxicity was manageable and outcomes were favorable compared with historical data.

Of the total patients, 70% (n = 21/30) experienced a severe (grade ≥3) infection at any point during the study. Additionally, 17% of patients (n = 5/30) experienced a severe infection specifically during the blinatumomab infusion cycle.

A critical finding was that no infection-related deaths occurred post-induction in the blinatumomab cohort. This is a significant improvement over the 4% infectious mortality rate observed in the Interfant-06 historical control group.

Out of 95 total infection episodes documented, the lowest number occurred during the blinatumomab phase. Viral infections were the most common (36%), predominantly upper respiratory infections (31.6%).

The use of supportive care was at the discretion of investigators. Intravenous immunoglobulin was administered to 19 patients (63%), with the most frequent use (40%) occurring during the blinatumomab cycle. Granulocyte-colony stimulating factor was administered to 5 patients (17%).

Study Overview and Rationale

Infant ALL is a rare disease, accounting for less than 5% of childhood ALL cases. Despite treatment intensification, infants with ALL, particularly those with a rearrangement of the KMT2A-r gene, face a poor prognosis. Relapse rates are high, with up to 66% occurring within the first year of diagnosis.

Blinatumomab is a bispecific T-cell engager that targets the CD19 protein on B cells and the CD3 protein on T cells, redirecting the patient's own T cells to trigger a cytotoxic response against the leukemia cells. While its efficacy has been demonstrated in relapsed/refractory settings and more recently in standard-risk childhood B-ALL, evidence for its use in frontline therapy for high-risk infant KMT2A-r ALL has been limited.

This was a prospective, single-arm, interventional, multicenter, phase 2 study. A randomized controlled trial was not pursued due to the historically poor outcomes associated with the standard Interfant-06 protocol alone.

In total,30 infants diagnosed with KMT2A-r CD19+ B-ALL at an age of less than 12 months were enrolled. The median age at diagnosis was 5 months. Patients were enrolled across 12 sites in Europe and Australia.

Patients were treated with the standard Interfant-06 chemotherapy protocol. A single cycle of blinatumomab (15 mcg/m², administered as a 28-day continuous infusion) was added after the induction phase.

Long-term outcomes were compared with a selected historical control group of 214 patients from the Interfant-06 study who met similar inclusion criteria but did not receive blinatumomab.

The median follow-up period for the study was 4.2 years (range, 3.2-6.0 years).

“The limitations to our study include study design, which did not allow for a randomized controlled trial of blinatumomab,” said Martins et al, authors of the study. “The poor outcomes of the previous Interfant-06 study were prohibitive of a control arm, and hence, we compared results with a clinically matched Interfant-06 cohort. In addition, a direct comparison of infectious events with the historical protocol was not possible because of the use of different adverse event classification systems.”

Pharmacokinetic Analysis

Pharmacokinetic (PK) analysis was performed on samples from 26 patients to determine blinatumomab's steady-state concentration and clearance in infants.

The mean steady-state concentration was 706 ± 194 pg/mL/d, and the median clearance was 0.89 L/h/m² (range, 0.57-2.66).

The PK parameters in infants were found to be comparable to those reported in older children and adults, suggesting that the drug is processed similarly across pediatric age groups. None of the tested covariates (age below or above 6 months) had a significant impact on blinatumomab clearance.

Next Steps in Research

Future research should explore the potential for replacing more intensive chemotherapy blocks with additional cycles of blinatumomab to further improve outcomes and reduce toxicity.

The results of contemporary studies, such as Interfant-21 (NCT05327894)² and COG AALL2321 (NCT06317662),³ are highly anticipated to provide further confirmation of blinatumomab's impact in this patient group.

REFERENCES

1.Martins M, de Lorenzo P, Kotecha R, et al. Sustained benefit of blinatumomab in infants with KMT2A-rearranged ALL: Long-term outcomes, toxicity, and pharmacokinetics. J Clin Oncol. Published January 8, 2026. Accessed January 26, 2026. doi: 10.1200/JCO-25-01806.

2.Interfant-21 treatment protocol for infants under 1 year with KMT2A-rearranged ALL or mixed phenotype acute leukemia (Interfant-21). ClinicalTrials.gov. Updated January 8, 2026. Accessed January 26, 2026. https://clinicaltrials.gov/study/NCT05327894

3.Testing the addition of the anti-cancer drug venetoclax and/or the anti-cancer immunotherapy blinatumomab to the usual chemotherapy treatment for infants with newly diagnosed KMT2A-rearranged or KMT2A-non-rearranged leukemia. ClinicalTrials.gov. Updated January 26, 2026. Accessed January 26, 2026. https://clinicaltrials.gov/study/NCT06317662