Follicular lymphoma (FL) is the most common subtype of indolent non-Hodgkin lymphoma (NHL), accounting for 20% to 30% of all NHL cases. Characterized by an indolent relapsing and remitting course, and with a cumulative risk of high-grade transformation, FL has historically been considered an incurable disease.

In an advanced stage, FL is usually treated with observation as long as the patient remains symptom-free and the disease does not progress, but symptomatic disease is treated with chemoimmunotherapy. An estimated 20% to 30% of patients will not respond to induction therapy or will experience disease progression while on maintenance therapy. For this group of patients, other options are available, including stem cell transplantation (SCT) and an increasing number of novel agents that have demonstrated significant efficacy in this setting. Despite these options, there is no universally accepted standard of care for relapsed FL, and studies that compare available treatment options are very limited.

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A review published in Bone Marrow Transplantation discussed conventional therapeutic options for relapsed FL (rFL) without high-grade transformation, the use of novel agents, and the role and timing of autologous SCT (ASCT) and allogeneic SCT (alloSCT) in this setting.

Novel Agents for Relapsed Disease

Although novel agents have shown promise in changing the treatment paradigm for FL, few randomized trials have been conducted and long-term follow-up data are lacking. In addition, even though these agents have been associated with impressive response rates, the response is typically not durable. Combinations of agents have improved responses but can result in excessive toxicity. These agents also tend to be very expensive, and cost and the need for continuous dosing represent a major challenge for the health care community.

One novel class of therapeutics are the second- and third-generation monoclonal antibodies (mAbs) that target CD20, such as ofatumumab, a fully humanized type I anti-CD20 mAb that has shown clinical responses in rFL and efficacy as a single agent. Results have been less robust in patients who are refractory to rituximab, but obinutuzumab combined with bendamustine has improved progression-free survival in patients previously treated with rituximab.

The use of antibody drug conjugates may be able to enhance the efficacy of mAbs by delivering cellular toxins directly to tumor cells. Polatuzumab vedotin, an anti-CD79b antibody conjugated to monomethyl aurostatin E, has shown efficacy as a single agent, and inotuzumab ozogamicin, an anti-CD22 antibody conjugated to calicheamicin, has also been investigated in this setting.