Research in context
Evidence before this study
We searched PubMed, the American Society of Hematology, the European Society of Hematology, the American Society of Clinical Oncology, and the European Society of Medical Oncology databases with for articles published in English between database inception and Sept 1, 2016, using the search terms “lymphoma, diffuse large B-cell”, “elderly”, “geriatric evaluation”, “prephase”, and “ofatumumab”. Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoid malignancy worldwide, with an incidence that steadily increases with age. In the next 50 years, the number of people aged 85 years and older is likely to quadruple. Since 2005, studies in elderly people have focused on this challenging health issue. These studies emphasised that very elderly patients require adequate therapeutic management, as shown in the case of DLBCL, for which lower doses provided a trade-off between efficacy and safety in patients aged 80 years and older. The Groupe d'Etude des Lymphomes Agressifs reported a prospective phase 2 study of attenuated chemotherapy (miniCHOP) with rituximab, a monoclonal antibody against CD20, at a conventional dose. Median overall survival was 29 months with 62% of patients having a complete response or unconfirmed complete response. Unfortunately, the study results also showed unacceptable early toxicity, occurring mainly during the first two cycles. The German High-Grade Non-Hodgkin Lymphoma Study Group strongly suggested that a pre-phase with vincristine and hydrocortisone could be useful to prevent early toxicity.
Added value of this study
We report an open-label, phase 2 study in patients aged 80 years and older with untreated CD20-positive DLBCL. Patients with DLBCL at any Ann Arbor stage and with any performance status were eligible. Patients received a pre-phase of vincristine and prednisone treatment before starting the first cycle of ofatumumab and miniCHOP combination treatment. The primary objective was to assess the efficacy of the treatment with overall survival. Our result confirms that a substantial proportion of patients with DLCBL aged 80 years and older could achieve a complete response with immunochemotherapy with a pre-phase of ofatumumab and miniCHOP. Additionally, a pre-phase seems to reduce both early death risk and toxicity.
Implications of all the available evidence
This finding shows the importance of the management of patients aged 80 years and older with a specifically designed protocol. Our results and those from the German High-Grade Non-Hodgkin Lymphoma Study Group are strongly in favour of a systematic pre-phase before immunochemotherapy for DLBCL in elderly people. The combination of miniCHOP plus a monoclonal antibody against CD20 with a pre-phase treatment could be the platform to design randomised clinical trials for DLBCL treatment in elderly people.