What Is the Best Strategy for Incorporating New Agents into the Current Treatment of Follicular Lymphoma?

Abstract

Although there is increasing knowledge about the pathobiology of follicular lymphoma (FL), the incorporation of new agents is challenged by the long clinical course and inherent heterogeneity of the disease. Furthermore, a longstanding concept in FL is that although most patients have an indolent initial phase of disease, this is typically followed by sequentially shorter remission durations and justifies the continued intense search for new rationally designed agents. Ideally, there would be personalized prognostic tools, preemptive target identification, and means to predict response in individual patients. Short of having these tools, one conceptual approach is to consider FL as a series of clinical disease states divided between treatment-naïve (low tumor burden and high tumor burden), relapsed (typically still chemoimmunotherapy-sensitive), and multiply relapsed (usually chemoimmunotherapy-resistant) disease. By applying what is known about the biology of FL along with the available agents, new treatment options can be better defined and tested within these clinical contexts. During the last few years, novel chemotherapeutics, biologic agents, monoclonal antibodies, antibody drug conjugates, and maintenance strategies are all either replacing or adding onto existing strategies. These new agents and approaches challenge the notion of inevitably shorter response durations, and offer hope of improved clinical outcomes compared with traditional sequential cytotoxic therapy.