Daratumumab in pediatric relapsed/refractory acute lymphoblastic leukemia or lymphoblastic lymphoma: the DELPHINUS study
Teena Bhatla, Laura Hogan, David T. Teachey, Franciso Bautista, John Moppett, Pablo Velasco, Concetta Micalizzi, Claudia Rössig, Neerav Shukla, Gil Gilad, Franco Locatelli, André Baruchel, Michel Zwaan, Natalie S. Bezler, Alba Rubio‐San‐Simón, David Taussig, Elizabeth A. Raetz, Zhengwei Mao, Brent L. Wood, Diana Alvarez Arias, Maria Krevvata, Ivo Nnane, Nibedita Bandyopadhyay, Lorena Lopez Solano, Robyn M. Dennis, Robin Carson, Ajay Vora
Abstract
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.