Phase 2 Study of Daratumumab in Relapsed/Refractory Mantle-Cell Lymphoma, Diffuse Large B-Cell Lymphoma, and Follicular Lymphoma

On the basis of encouraging preclinical studies, this phase 2 trial assessed daratumumab monotherapy in relapsed/refractory non-Hodgkin lymphoma subtypes, including relapsed/refractory diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and mantle-cell lymphoma (MCL). The trial screened 138 patients and enrolled 15 patients with DLBCL, 16 with FL, and 5 with MCL. The low overall response rate caused the study to meet the predefined futility criteria. No new safety signals were observed. Background: Daratumumab is a CD38 monoclonal antibody approved for treating relapsed/refractory and newly diagnosed multiple myeloma. Preclinical daratumumab studies demonstrated cytotoxic activity and reduced tumor growth in B-cell non-Hodgkin lymphoma (NHL) subtypes, including diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and mantle-cell lymphoma (MCL). Patients and Methods: This was a phase 2, open-label, multi-center, 2-stage trial. Patients with relapsed/refractory DLBCL, FL, or MCL with >= 50% CD38 expression were eligible for stage 1. Daratumumab (16 mg/kg; 28-day cycles) was administered intravenously weekly for 2 cycles, every 2 weeks for 4 cycles, and every 4 weeks thereafter. Overall response rate was the primary end point. Pharmacokinetic and safety were also evaluated. Stage 2 was planned to further assess daratumumab in larger populations of NHL subtypes if futility criteria were not met. The study was registered with ClinicalTrials.gov (NCT02413489). Results: The trial screened 138 patients resulting in accrual of 15 patients with DLBCL, 16 with FL, and 5 with MCL. Median CD38 expression across treated patients was 70%. Overall response rate was 6.7%, 12.5%, and not evaluable in DLBCL, FL, and MCL cohorts, respectively. The most common grade 3/4 treatment-emergent adverse event was thrombocytopenia (11.1%), and 4 (11.1%) patients discontinued treatment because of treatment-emergent adverse events. Infusion-related reactions occurred in 72.2% of patients (3 patients with grade 3; no grade 4). Conclusion: In NHL, the safety and pharmacokinetics of daratumumab were consistent with myeloma studies. Screen-fail rates were high, prespecified futility thresholds were met in 2 cohorts, and the study was terminated. Studies in other hematologic malignancies and amyloidosis are ongoing.