From drug discovery to biomarker-driven clinical trials in lymphoma

Over the past three decades, the pathological classification of lymphoma has substantially improved. The early Rappaport classification included a handful of subtypes that did not reflect the cell of origin and, not surprisingly, resulted in diagnostic inaccuracies. The WHO currently classifies lymphoma into 30 major distinctive types. While this classification improved the accuracy and consistency of the histological diagnosis of lymphoma, it had little impact on advancing drug development or improving the cure rate of this disease. One reason for this lack of improvement is that recent developments in cancer genomics show these histopathological subtypes to be heterogeneous. Basing treatment decisions on histopathological subtypes is inefficient as it groups different underlying molecular characteristics into one category. Such a strategy exposes many patients to potentially toxic drugs without providing benefits. The recent approval of two new cancer drugs with companion diagnostics to allow selection and treatment of patients with melanoma and non-small-cell lung cancer has raised hope that a similar approach may also expedite successful drug development in lymphoma. We review the current status of biomarker development in lymphoma, and discuss novel biomarker-directed clinical trial designs for lymphoma.