brentuximab vedotin

b-cell lymphoma

hodgkin lymphoma

cell lymphoma

directors advisory committees

research funding

non-hodgkin lymphoma

clinical trial

stem cell

Blood

BACKGROUND: CD30 is a cell membrane protein detectable by immunohistochemistry (IHC) in approximately 80% of primary mediastinal large B-cell (PMBL), 20% of diffuse large B-cell (DLBCL) and 100% of grey zone lymphomas (GZL). Brentuximab vedotin (BV) is a CD30-directed immunoconjugate with established efficacy in relapsed Hodgkin and some T-cell lymphomas. This targeted agent may have a role in management of patients (pts) with CD30+ B-cell non-Hodgkin lymphomas (NHL).  METHODS: We designed an open label, multicenter phase I/II trial using BV administered concurrently with R-CHP (rituximab 375 mg/m2, cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2 on Day [D] 1 and prednisone 100 mg on D1-5) every 3 weeks for 6 cycles (C) as frontline treatment for CD30+ PMBL, DLBCL and GZL. Pts with any Ann Arbor stage and at least equivocal CD30 expression on IHC were eligible. Consolidative radiation (RT) was allowed after completion of study at discretion of the treating physician. Phase I utilized a 3+3 de-escalation design with starting dose of BV at 1.8 mg/kg in combination with R-CHP. G-CSF use was based on institutional policies. The primary objective of phase I was assessment of safety and dose limiting toxicity (DLT) defined as any grade (G) 3/4 non-hematologic toxicity observed in C1 requiring dose delay >14 days from the planned D1 of C2. The primary phase II objectives were overall response (ORR) and complete response (CR) rates with secondary endpoints of progression free survival (PFS), overall survival (OS), and safety. Explorative analyses include correlation of response with quantitative CD30 expression and results of a customized Nanostring panel. Revised Response Criteria were used for response assessment (Cheson, 2007). Enrollment began in 1/2014 and completed in 6/2017.  RESULTS: We enrolled 33 treatment naive pts at 3 centers. One pt was re-classified from GZL to HL prior to starting therapy and one pt withdrew consent. The remaining 31 pts included 23 (74%) with PMBL, 6 DLBCL (19%) and 2 GZL (7%). Median a...

Brentuximab Vedotin with R-CHP Chemotherapy As Frontline Treatment for Patients with CD30 Positive Primary Mediastinal Large B-Cell, Diffuse Large B-Cell, and Grey Zone Lymphomas: Results of a Phase I/II Multisite Trial