Treatment of diffuse large B-cell lymphoma: a risk-based approach

Advances in molecular biology have provided an increased understanding of the heterogeneity of diffuse large B-cell lymphoma, allowing multiple clinical and biologic prognostic factors to be elucidated. Recently, the addition of rituximab to CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone) has been adopted as the new standard of care, representing the first major improvement in therapy in 2 decades. Although outcomes have markedly improved, patients with lymphoma that is not cured with this standard first-line therapy continue to pose a difficult challenge. Early identification of patients at high risk would allow alternative treatment strategies to be considered in a risk-based management approach. Accurate risk assessment will require all previously recognized prognostic indicators to be revalidated in the era of immunochemotherapy. Although the International Prognostic Index remains predictive, it no longer distinguishes a subgroup with < 50% chance of survival. Many molecular prognostic markers, such as Bcl-2 and Bcl-6 protein expression, no longer appear predictive of outcome. Early positron emission tomography scanning is a powerful independent predictive tool that will likely be relied on more frequently in the future. Finally, the role of increased dose intensity or dose density will need to be reevaluated for combinations that include rituximab. Alternative treatment strategies and newer therapies will need to be explored in the context of clinical trials.