Gilles Salles1, Ajay K Gopal2, Monique C Minnema3, Karen Wakamiya4, Huaibao Feng5, Jordan M Schecter5, Michael Wang6. 1. Hématologie, Hospices Civils de Lyon and Université de Lyon, Lyon, France. 2. Department of Medicine, University of Washington, Seattle, WA. 3. Department of Hematology, UMC Utrecht Cancer Center, Utrecht, The Netherlands. 4. Agilent Technologies Inc, Carpinteria, CA. 5. Janssen Research & Development, Raritan, NJ. 6. Division of Cancer Medicine, Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX. Electronic address: miwang@mdanderson.org.
Abstract
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, multicenter, 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.
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, multicenter, 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.
Authors: Thomas G Martin; Kathryn Corzo; Marielle Chiron; Helgi van de Velde; Giovanni Abbadessa; Frank Campana; Malini Solanki; Robin Meng; Helen Lee; Dmitri Wiederschain; Chen Zhu; Alexey Rak; Kenneth C Anderson Journal: Cells Date: 2019-11-26 Impact factor: 6.600
Authors: Xu Wang; Xinfang Yu; Wei Li; Praveen Neeli; Ming Liu; Ling Li; Mingzhi Zhang; Xiaosheng Fang; Ken H Young; Yong Li Journal: J Exp Clin Cancer Res Date: 2022-06-28
Authors: Marilyn T Nedumcheril; Robert A DeSimone; Sabrina E Racine-Brzostek; Ok Kyong Chaekal; Ljiljana V Vasovic Journal: J Blood Med Date: 2021-05-25