P360: EFFICACY AND SAFETY OF DARATUMUMAB IN PEDIATRIC AND YOUNG ADULT PATIENTS WITH RELAPSED/REFRACTORY T-CELL ACUTE LYMPHOBLASTIC LEUKEMIA OR LYMPHOBLASTIC LYMPHOMA: RESULTS FROM PHASE 2 DELPHINUS STUDY

Abstract

Background: Approximately 15-20% of pediatric patients with T-cell acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LL) will be refractory to/relapse after frontline treatment; relapsed disease is associated with poor outcomes. In a phase 2 study, 2 of 7 (28.6%) patients with T-cell ALL in first relapse achieved a complete response (CR) using the vincristine, prednisone, PEG-asparaginase, and doxorubicin (VPLD) reinduction backbone. Daratumumab (DARA), a human IgGκ monoclonal antibody targeting CD38 approved for treating multiple myeloma, has shown preclinical efficacy in ALL models. Aims: Here we report the initial results of DARA plus VPLD in pediatric and young adult patients with relapsed/refractory T-cell ALL or LL enrolled in the phase 2, open-label DELPHINUS study. Methods: Eligible patients were aged 1-30 y, had T-cell ALL or LL in first relapse or refractory to 1 prior induction/consolidation regimen, and had a performance status ≥70. DARA (16 mg/kg IV QW) was given with VPLD in Cycle 1 and with methotrexate, cyclophosphamide, cytarabine, and 6-mercaptopurine in Cycle 2. Patients received age/risk-adjusted intrathecal therapy. Response was measured at the end of each cycle by local bone marrow morphology. The primary endpoint for ALL patients was CR rate in pediatric patients at the end of Cycle 1. Patients achieving CR after Cycles 1 or 2 could proceed to allogeneic HSCT off study. Overall response rate (ORR) was defined as CR or CR with incomplete hematological recovery (CRi) at any time before start of subsequent therapy or HSCT. Minimal residual disease (MRD) negativity (<0.01%) at any time before disease progression, start of subsequent therapy, or HSCT was centrally reviewed by flow cytometry. Results: Twenty-four pediatric (age 1-17 y) and 5 young adult (age 18-30 y) ALL patients and 10 LL patients (age 1-30 y) received ≥1 DARA dose. Median (range) age was 10.0 (2-25) y (ALL) and 14.5 (5-22) y (LL); median (range) time from initial diagnosis to first study treatment was 2.0 (0.1-6.1) y (ALL) and 0.8 (0.5-6.0) y (LL). Pediatric ALL patients received a median (range) of 2 (1-3) treatment cycles; young adult ALL patients and LL patients each received 2 (1-2). Among pediatric ALL patients, 10 (41.7%) patients (90% CI, 24.6-60.3) achieved CR at the end of Cycle 1. ORR was 83.3% (CR, 13 [54.2%] patients; CRi, 7 [29.2%] patients) in pediatric and 60.0% (all CR) in young adult ALL patients and 40.0% (all CR) in LL patients. Ten (41.7%) pediatric ALL patients achieved MRD negativity. All pediatric ALL patients had a grade 3/4 TEAE. No pediatric ALL pt discontinued DARA primarily due to AEs and 1 (4.2%) died due to TEAEs (brain edema and hepatic failure) attributed to study treatment but unrelated to DARA. Summary/Conclusion: The addition of DARA to VPLD in pediatric and young adult patients with relapsed/refractory T-cell ALL or LL showed initial activity, generating improved response rates compared to those achieved with backbone therapy alone, with a manageable safety profile.