Join Anas Younes, MD, and Andrew Zelenetz, MD, PhD, as they present their multidisciplinary expertise on a range of cases pertaining to follicular lymphoma.

Follicular lymphoma is diagnosed in approximately 20% of NHL cases and represents the most common form of indolent NHL. Although FL is characterized by an indolent course of disease, it remains incurable with currently available therapies. The anti-CD20 monoclonal antibody rituximab combined with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy /CHOP-like regimens (R-CHOP or R-chemotherapy) is the standard frontline treatment in patients with previously untreated FL. The past year has seen important advances in the standard of care for frontline FL, which builds upon the efficacy seen with R-CHOP regimens. These advances include a new chemoimmunotherapy combination regimen with bendamustine and rituximab, which demonstrated superior progression-free survival (PFS) in comparison to R-CHOP, and the incorporation of rituximab as maintenance treatment after frontline remission-induction therapy with R-chemotherapy, which also demonstrated prolonged PFS in comparison to no maintenance (i.e., observation alone after remission induction therapy).

In addition, other post-induction treatment strategies, such as consolidation with radioimmunoconjugates, have shown improvements in PFS outcomes in the frontline setting. The treatment of patients with relapsed/refractory FL, particularly rituximab-refractory disease, remains a clinical challenge. Bendamustine, an alkylating agent with a purine-like component, is currently approved for the treatment of rituximab-refractory FL. Other agents, such as newer anti-CD20 monoclonal antibodies with potentially enhanced cytotoxic activity relative to rituximab (e.g., GA-101, ofatumumab) are under investigation for use in relapsed/refractory FL, including in rituximab-refractory disease. The immunomodulating agent lenalidomide has shown promising single-agent activity in patients with relapsed/refractory FL. In addition, the combination of the proteasome inhibitor bortezomib and rituximab has demonstrated activity in relapsed/refractory FL in phase II studies,and a randomized phase III trial is underway to determine the efficacy and safety of this combination compared with rituximab alone in patients with relapsed FL. The sNDA for bortezomib in combination with rituximab in the treatment of relapsed FL was recently submitted to the FDA. A three-drug regimen combining bendamustine, bortezomib, and rituximab is also being evaluated in clinical studies in relapsed/refractory FL.

Precise diagnosis of this disease is critical to determining the appropriate treatment.  Misdiagnosis can result in inappropriate and ineffective treatment. In patients with lymphoma, clinicians must know the exact diagnosis and whether or not there are indications for treatment. For clinicians who do not work with lymphoma on a regular basis or do not have access to an expert hematopathologist, identifying the sub-type of lymphoma and the appropriate treatments is a challenge. Physicians need to be aware of the various options available and the precise indications for their use.  Additionally, as new compounds are developed, their use will need to be incorporated into clinical decision making.