Daratumumab in pediatric relapsed/refractory acute lymphoblastic leukemia or lymphoblastic lymphoma: the DELPHINUS study.

Autor:	Bhatla T; Department of Pediatrics, Children's Hospital of New Jersey, Newark Beth Israel Medical Center, Newark, NJ., Hogan LE; Department of Pediatrics, Stony Brook Children's, Stony Brook, NY., Teachey DT; Division of Oncology, Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA., Bautista F; Department of Pediatric Hematology-Oncology, Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.; Department of Pediatric Hematology-Oncology, Hospital Infantil Universitario Niño Jesús, Madrid, Spain., Moppett J; Paediatric Haematology, Bristol Royal Hospital for Children, Bristol, United Kingdom., Velasco Puyó P; Department of Pediatric Hematology-Oncology, Vall d'Hebron Hospital, Barcelona, Spain., Micalizzi C; Clinical Experimental Haematology Unit, IRCCS Istituto Giannina Gaslini, Genova, Italy., Rossig C; Department of Pediatric Hematology and Oncology, University Children's Hospital Münster, Münster, Germany., Shukla N; Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY., Gilad G; Department of Pediatric Hematology-Oncology, Schneider Children's Medical Center of Israel, Petach Tikva, Israel.; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel., Locatelli F; Department of Pediatric Hematology and Oncology, IRCCS Ospedale Pediatrico Bambino Gesù, Catholic University of the Sacred Heart, Rome, Italy., Baruchel A; Pediatric Hematology and Immunology Department, Robert Debré University Hospital, Assistance Publique-Hôpitaux de Paris and Université de Paris Cité, Paris, France., Zwaan CM; Department of Pediatric Hematology-Oncology, Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.; Department of Pediatric Oncology, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands., Bezler NS; Division of Hematology and Oncology, Connecticut Children's, University of Connecticut School of Medicine, Hartford, CT., Rubio-San-Simón A; Department of Pediatric Hematology-Oncology, Hospital Infantil Universitario Niño Jesús, Madrid, Spain., Taussig DC; Centre for Molecular Pathology, The Royal Marsden Hospital, Institute of Cancer Research, Sutton, United Kingdom., Raetz EA; Department of Pediatrics, New York University Langone Health, New York, NY., Mao ZJ; Department of Laboratory Medicine, University of Washington, Seattle, WA., Wood BL; Department of Laboratory Medicine, University of Washington, Seattle, WA., Alvarez Arias D; Janssen Research and Development, LLC, Spring House, PA., Krevvata M; Janssen Research and Development, LLC, Spring House, PA., Nnane I; Janssen Research and Development, LLC, Spring House, PA., Bandyopadhyay N; Janssen Research and Development, LLC, Raritan, NJ., Lopez Solano L; Janssen Research and Development, LLC, Raritan, NJ., Dennis RM; Janssen Research and Development, LLC, Raritan, NJ., Carson R; Janssen Research and Development, LLC, Spring House, PA., Vora A; Department of Haematology, Great Ormond Street Hospital for Children, London, United Kingdom.
Jazyk:	angličtina
Zdroj:	Blood [Blood] 2024 Nov 21; Vol. 144 (21), pp. 2237-2247.
DOI:	10.1182/blood.2024024493
Abstrakt:	Abstract: Patients with relapsed/refractory acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LL) have poor outcomes compared with newly diagnosed, treatment-naïve patients. The phase 2, open-label DELPHINUS study evaluated daratumumab (16 mg/kg IV) plus backbone chemotherapy in children with relapsed/refractory B-cell ALL (n = 7) after ≥2 relapses, and children and young adults with T-cell ALL (children, n = 24; young adults, n = 5) or LL (n = 10) after first relapse. The primary end point was complete response (CR) in the B-cell ALL (end of cycle 2) and T-cell ALL (end of cycle 1) cohorts, after which patients could proceed off study to allogeneic hematopoietic stem cell transplant (HSCT). Seven patients with advanced B-cell ALL received daratumumab with no CRs achieved; this cohort was closed because of futility. For the childhood T-cell ALL, young adult T-cell ALL, and T-cell LL cohorts, the CR (end of cycle 1) rates were 41.7%, 60.0%, and 30.0%, respectively; overall response rates (any time point) were 83.3% (CR + CR with incomplete count recovery [CRi]), 80.0% (CR + CRi), and 50.0% (CR + partial response), respectively; minimal residual disease negativity (<0.01%) rates were 45.8%, 20.0%, and 50.0%, respectively; observed 24-month event-free survival rates were 36.1%, 20.0%, and 20.0%, respectively; observed 24-month overall survival rates were 41.3%, 25.0%, and 20.0%, respectively; and allogeneic HSCT rates were 75.0%, 60.0%, and 30.0%, respectively. No new safety concerns with daratumumab were observed. In conclusion, daratumumab was safely combined with backbone chemotherapy in children and young adults with T-cell ALL/LL and contributed to successful bridging to HSCT. This trial was registered at www.clinicaltrials.gov as NCT03384654. (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)
Databáze:	MEDLINE
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