The combination of blinatumomab and chemotherapy appears safe and effective in infants with KMT2A-rearranged acute lymphoblastic lymphoma (ALL), according to researchers.

Patients who received the combination had superior overall survival (OS) and disease-free survival (DFS) when compared with historical control patients who received chemotherapy alone. 

In addition, the toxicity profile of blinatumomab was similar to that observed in other age groups. The researchers reported these findings in The New England Journal of Medicine.

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Patient and Treatment Details

This phase 2 trial included 30 patients younger than 1 year of age who had newly diagnosed, KMT2A-rearranged ALL. The patients received 1 month of the same induction therapy used in the Interfant-06 trial (cyclophosphamide, cytarabine, and mercaptopurine). 

After induction, patients received 1 cycle of blinatumomab as a 4-week continuous infusion, with dexamethasone beforehand and intrathecal prophylaxis (methotrexate and prednisolone) on day 15. 

Patients then received another course of the induction regimen, followed by MARMA (high-dose cytarabine, high-dose methotrexate, mercaptopurine, and asparaginase), OCTADAD (vincristine, dexamethasone, asparaginase, daunorubicin, thioguanine, cytarabine, and cyclophosphamide), and maintenance (mercaptopurine and methotrexate). 

Patients with high-risk disease and those who had medium-risk disease with minimal residual disease (MRD) of at least 5 x 10-4 before OCTADAD were allowed to undergo hematopoietic stem cell transplant in first complete remission. 


The median follow-up was 26.3 months. The primary endpoint was any potentially or definitely related adverse event (AE) that resulted in blinatumomab discontinuation or death. 

The primary endpoint was not met, and all patients received the full 28-day course of blinatumomab. There were a total of 78 AEs, including 16 grade 3 or higher AEs. The most common grade 3 or higher AEs were anemia (17%), febrile neutropenia (7%), neutropenia (7%), and elevated γ-glutamyltransferase levels (7%).

The researchers compared efficacy results in these 30 patients to results in 214 historical control patients from the Interfant-06 trial who received the same treatment but without blinatumomab. Baseline characteristics were similar between the 2 groups.

In the current trial, the rate of MRD negativity was 53% after 2 weeks of blinatumomab and 53% after 4 weeks. Of 22 patients who were MRD-positive at the end of induction, 9 were MRD-negative after completing blinatumomab. 

Before starting MARMA, 93% of patients in the current trial and 83% of the historical control group had MRD levels below 5 x 10-4  (P =.26). All patients in the current trial had MRD levels below 5 x 10-4 before OCTADAD, compared with 83% of patients in the historical control group.

The 2-year OS rate was 93.3% in the current trial and 65.8% in the historical control group (hazard ratio [HR], 0.15; 95% CI, 0.04-0.62). The 2-year DFS rates were 81.6% and 49.4%, respectively (HR, 0.22; 95% CI, 0.09-0.34).

In the current trial, 4 patients relapsed, but 3 of them were in complete remission at last follow-up. One patient died in first remission, but the death was deemed unrelated to blinatumomab.

Although longer follow-up is needed, the researchers noted that “the low incidence of relapse after treatment with blinatumomab is remarkable, given that, in historical controls, relapses occur frequently and early during therapy.”

“In this study, adding blinatumomab to the standard chemotherapy backbone in infants with newly diagnosed KMT2A-rearranged ALL was feasible and appeared to be safe,” the researchers concluded. 

Disclosures: This research was partly supported by Amgen. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


van der Sluis IM, de Lorenzo P, Kotecha RS, et al. Blinatumomab added to chemotherapy in infant lymphoblastic leukemia. N Eng J Med. Published online April 27, 2023. doi:10.1056/NEJMoa2214171