Combined miniCHOP (reduced-dose cyclophosphamide, doxorubicin, vincristine, and prednisone) and treatment with the fully-human anti-CD20 monoclonal antibody ofatumumab is associated with improved overall survival among elderly patients diagnosed with diffuse large B-cell lymphoma (DLBCL), according to an open-label, single-arm, phase II clinical study conducted in France and Belgium. The findings were published in The Lancet Haematology by the Lymphoma Study Association (LYSA).
The findings follow a 2011 LYSA study—published in The Lancet Oncology—of combined rituximab and miniCHOP that had found a 2-year overall survival rate of 59% but a high rate of early toxicities.
“Our results suggest that, in patients older than 80 years with DLBCL, ofatumumab and pre-phase treatment seem to improve overall survival compared with the previously-reported data,” the authors reported in The Lancet Haematology. “The combination of pre-phase treatment, a monoclonal antibody against CD20, and miniCHOP can be considered a new treatment platform for use in randomized clinical trial design for DLBCL treatment in patients older than 80 years.”
An estimated 30% of patients diagnosed with DLBCL are older than age 70 years at diagnosis. Ofatumumab is a novel, second-generation monoclonal antibody. Like rituximab, it targets CD20 antigen, albeit using a distinct epitope.
During 2010 and 2011, the authors enrolled 120 patients with previously-untreated CD20-positive DLBCL. Patients were administered a “pre-phase” of oral vincristine and oral prednisone before receiving their first cycle of intravenous ofatumumab plus miniCHOP. The combination therapy involved ofatumumab (a total dose of 1000 mg), doxorubicin (25 mg/m2), cyclophosphamide (400 mg/m2), and vincristine (1 mg) on day 1 of each cycle, followed by 40 mg/m2 of oral prednisone on days 1–5, the authors reported.
“Ofatumumab was administered with 1000 mg of paracetamol and 50 mg of diphenhydramine,” they reported.
At an average follow-up of 26.8 months, median overall survival for the intent-to-treat population had not yet been reached but the 2-year overall survival was 64.7% (compared to 59% in the 2011-reported study). A total of 28 patients died from lymphoma in that time.
Common toxicities included grade 3/4 neutropenia (21% of patients), febrile neutropenia (6%), anemia (5%), and thrombocytopenia (2%).
The study was funded by LYSA and GlaxoSmithKline.