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.