Blinatumomab Is Safe and Efficacious in Infant Acute Lymphoblastic Leukemia

Despite the improvements to event-free survival for older children with acute lymphoblastic leukemia (ALL), infants diagnosed with KMT2A-rearranged ALL within their first year of life have an event-free survival below 40%. Ninety percent of disease relapse occurs within the first 2 years of diagnosis, indicating the need for better therapies for this disease. Blinatumomab, a bispecific T-cell engager molecule that targets CD19, was demonstrated to be safe and effective after chemotherapy in older children and adults with relapsed ALL; therefore, van der Sluis and colleagues sought to determine the safety and efficacy of blinatumomab added to the chemotherapy backbone used in the Interfant-06 study in 30 newly diagnosed infants with KMT2A-rearranged ALL in a phase II clinical trial. The primary endpoint of this trial was clinically relevant toxic side effects, which was defined as any toxic effect that was attributable to blinatumomab and resulted in discontinuation of treatment or death. Secondary endpoints included toxicity and antileukemic activity. Toxic effects that met the primary endpoint were not observed with all patients receiving the full course of blinatumomab. Nine patients had 10 serious adverse events including fever, infection, hypertension, and vomiting, with no fatal adverse events being reported. Evaluation of safety revealed that 28 of 30 patients (93%) were minimal residual disease (MRD)–negative or had low MRD levels (<5 × 10⁻⁴, i.e., <5 leukemic cells per 10,000 normal cells) at the end of blinatumomab infusion, and after a median follow-up of 26.3 months, the 2-year disease-free survival was 81.6% compared to the 49.4% after the chemotherapy used in the Interfant-06 trial, which was used as a historical control. Moreover, overall survival was demonstrated as 93.3% as compared to the historical control, which had an overall survival of 65.8%. In summary, the results of this trial indicate both the safety and efficacy of blinatumomab plus chemotherapy in newly diagnosed infant KMT2A-rearranged ALL and suggest that further investigation is warranted.

van der Sluis IM, de Lorenzo P, Kotecha RS, Attarbaschi A, Escherich G, Nysom K, et al. Blinatumomab added to chemotherapy in infant lymphoblastic leukemia. N Engl J Med 2023;388:1572–81.

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