• Inge M van der Sluis, Paola de Lorenzo, Rishi S Kotecha, Andishe Attarbaschi, Gabriele Escherich, Karsten Nysom, Jan Stary, Alina Ferster, Benoit Brethon, Franco Locatelli, Martin Schrappe, Peggy E Scholte-van Houtem, Maria G Valsecchi, and Rob Pieters.
• From the Princess Máxima Center for Pediatric Oncology (I.M.S., P.E.S.-H., R.P.), and the Dutch Childhood Oncology Group (I.M.S., R.P.) - both in Utrecht, the Netherlands; Tettamanti Center (P.L.) and Biostatistics and Clinical Epidemiology (M.G.V.), Fondazione IRCCS San Gerardo dei Tintori, Monza, the School of Medicine and Surgery, University of Milano-Bicocca, Milan (M.G.V.), and the Department of Pediatric Hematology-Oncology and Cell and Gene Therapy, IRCCS Ospedale Pediatrico Bambino Gesù, Catholic University of the Sacred Heart, Rome (F.L.) - all in Italy; Australian and New Zealand Children's Hematology and Oncology Group, Perth Children's Hospital (R.S.K.), Telethon Kids Cancer Centre, Telethon Kids Institute, University of Western Australia (R.S.K.), and Curtin Medical School, Curtin University (R.S.K.) - all in Perth, WA, Australia; St. Anna Children's Hospital, Department of Pediatric Hematology and Oncology, Medical University of Vienna, and St. Anna Children's Cancer Research Institute - both in Vienna (A.A.); the German Cooperative Study Group for Childhood Acute Lymphoblastic Leukemia, Hamburg (G.E.) the Clinic of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg (G.E.), and the ALL-Berlin-Frankfurt-Münster (BFM) Group, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel (M.S.) - all in Germany; the Department of Pediatrics and Adolescent Medicine, Rigshospitalet, University Hospital, Copenhagen (K.N.); Czech Working Group for Pediatric Hematology (J.S.) and CLIP (Childhood Leukemia Investigation Prague), Department of Pediatric Hematology and Oncology, Second Faculty of Medicine, Charles University and University Hospital Motol (J.S.) - all in Prague, Czech Republic; Hôpital Universitaire des Enfants Reine Fabiola, Brussels (A.F.); and the Department of Pediatric Hematology, University Robert Debre Hospital, Assistance Publique-Hôpitaux de Paris, Paris (B.B.).
• N. Engl. J. Med. 2023 Apr 27; 388 (17): 157215811572-1581.

BackgroundKMT2A-rearranged acute lymphoblastic leukemia (ALL) in infants is an aggressive disease with 3-year event-free survival below 40%. Most relapses occur during treatment, with two thirds occurring within 1 year and 90% within 2 years after diagnosis. Outcomes have not improved in recent decades despite intensification of chemotherapy.MethodsWe studied the safety and efficacy of blinatumomab, a bispecific T-cell engager molecule targeting CD19, in infants with KMT2A-rearranged ALL. Thirty patients younger than 1 year of age with newly diagnosed KMT2A-rearranged ALL were given the chemotherapy used in the Interfant-06 trial with the addition of one postinduction course of blinatumomab (15 μg per square meter of body-surface area per day; 28-day continuous infusion). The primary end point was clinically relevant toxic effects, defined as any toxic effect that was possibly or definitely attributable to blinatumomab and resulted in permanent discontinuation of blinatumomab or death. Minimal residual disease (MRD) was measured by polymerase chain reaction. Data on adverse events were collected. Outcome data were compared with historical control data from the Interfant-06 trial.ResultsThe median follow-up was 26.3 months (range, 3.9 to 48.2). All 30 patients received the full course of blinatumomab. No toxic effects meeting the definition of the primary end point occurred. Ten serious adverse events were reported (fever [4 events], infection [4], hypertension [1], and vomiting [1]). The toxic-effects profile was consistent with that reported in older patients. A total of 28 patients (93%) either were MRD-negative (16 patients) or had low levels of MRD (<5×10-4 [i.e., <5 leukemic cells per 10,000 normal cells], 12 patients) after the blinatumomab infusion. All the patients who continued chemotherapy became MRD-negative during further treatment. Two-year disease-free survival was 81.6% in our study (95% confidence interval [CI], 60.8 to 92.0), as compared with 49.4% (95% CI, 42.5 to 56.0) in the Interfant-06 trial; the corresponding values for overall survival were 93.3% (95% CI, 75.9 to 98.3) and 65.8% (95% CI, 58.9 to 71.8).ConclusionsBlinatumomab added to Interfant-06 chemotherapy appeared to be safe and had a high level of efficacy in infants with newly diagnosed KMT2A-rearranged ALL as compared with historical controls from the Interfant-06 trial. (Funded by the Princess Máxima Center Foundation and others; EudraCT number, 2016-004674-17.).Copyright © 2023 Massachusetts Medical Society.

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