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

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.

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Journal
Blood
Published
2024-08-19
DOI
https://doi.org/10.1182/blood.2024024493
Citations
41
Primary Topic
Acute Lymphoblastic Leukemia research
Type
article
Field-Weighted Citation Impact
22.26

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article

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

John Moppett, André Baruchel, Brent Lee Wood, Pablo Velasco et al.
41 citations
Blood
Acute Lymphoblastic Leukemia research
22.26
article

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

John Moppett, André Baruchel, Brent Lee Wood, Pablo Velasco, Claudia Rössig, Neerav Shukla, Franco Locatelli, Robyn M. Dennis, Elizabeth A. Raetz, Ivo Nnane, David T. Teachey, Nibedita Bandyopadhyay, Teena Bhatla, David Taussig, Michel Zwaan, Robin L. Carson, Ajay Vora, Concetta Micalizzi, Diana Alvarez Arias, Natalie S. Bezler, Lorena Lopez Solano, Alba Rubio‐San‐Simón, Laura Hogan, Gil Gilad, Maria Krevvata, Zhengwei Mao, Franciso Bautista
article en
41 citations

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.

BloodVol. 144(21)
Università Cattolica del Sacro Cuore (IT), Newark Beth Israel Medical Center (US), Memorial Sloan Kettering Cancer Center (US), Children's Hospital of Philadelphia (US), University of Connecticut (US), Institute of Cancer Research (GB), Tel Aviv University (IL), University of Washington (US), Université Paris Cité (FR), Great Ormond Street Hospital (GB), Istituto Giannina Gaslini (IT), Bristol Royal Hospital for Children (GB), NYU Langone Health (US), Assistance Publique – Hôpitaux de Paris (FR), Springhouse (US), Connecticut Children's Medical Center (US), University Hospital Münster (DE), Schneider Children's Medical Center (IL), Hospital Infantil Universitario Niño Jesús (ES), Royal Marsden Hospital (GB), Bambino Gesù Children's Hospital (IT), Princess Máxima Center (NL), Vall d'Hebron Hospital Universitari (ES), Ormond (United States) (US), Erasmus MC - Sophia Children’s Hospital (NL), Stony Brook Children's Hospital (US), Janssen (United States) (US), Istituti di Ricovero e Cura a Carattere Scientifico (IT), Hartford Financial Services (United States), University College London (GB), University of Pennsylvania (US)
Amgen, Bristol-Myers Squibb, Pfizer, Sanofi, Yale University, Gilead Sciences, Vertex Pharmaceuticals, Jazz Pharmaceuticals, Incyte, Syndax Pharmaceuticals, Servier, Swedish Orphan Biovitrum, EUSA Pharma, Genentech, Daiichi Sankyo Europe
Good health and well-being
Openalex Percentile: Top 0%
Acute Lymphoblastic Leukemia research
22.26
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