Current and Prospective Treatment Strategies for Follicular Lymphoma

Follicular lymphoma (FL) is a common indolent lymphoproliferative malignancy often characterized by peripheral lymphadenopathy, in addition to varying degrees of splenomegaly and bone marrow involvement. The initial presentation is usually asymptomatic, lacking the presence of constitutional symptoms. Due to potential aggressive transformation, the demand for novel treatment strategies is high.^1,2

In a review article published in the British Journal of Haematology, Carla Casulo, MD, of the department of medicine at the University of Rochester in New York, summarized current literature surrounding the management of FL. She also reviewed some novel treatment strategies recently approved by the US Food and Drug Administration (FDA).

Lori A Leslie, MD, of the John Theurer Cancer Center in Hackensack, New Jersey, told Hematology Advisor, “With a rapidly increasing number of novel therapies available for patients with relapsed/refractory FL, the most difficult part of FL management [is] choosing the best of many available options.”

Pathogenesis and Treatment of Follicular Lymphoma

Despite major advances in treatment, the underlying mechanisms causing malignant transformation of normal B lymphocytes into FL are still being elucidated. Although specific genetic abnormalities, such as the t(14;18) IGH-BCL2 translocation, have been recognized in up to 85% of patients with the condition, multiple genetic events are likely implicated. Recent findings have suggested that abnormal T-cell function within the cellular microenvironment may also be involved in disease pathogenesis.^1,2

Traditionally, frontline treatment for patients with low tumor burden disease has been observation or rituximab. Both strategies have demonstrated similar outcomes, with some studies showing no differences in overall survival (OS) with either approach.¹

In cases of high tumor burden FL, patients are often symptomatic and typically receive treatment with chemoimmunotherapy combinations, such as rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or bendamustine. The role of these regimens in providing durable responses has been established on the basis of many randomized trials.¹

The anti-CD20 monoclonal antibody obinutuzumab may also be used in the frontline setting. In comparison with rituximab, obinutuzumab-based regimens have demonstrated marginally better progression-free survival (PFS). Despite these benefits, higher-grade toxicities have been seen in regimens with an obinutuzumab-based backbone.¹

“I base the decision to use obinutuzumab-based [induction compared with] rituximab-based induction on the individual chemotherapy backbone, patient age, and comorbid conditions,” wrote Dr Casulo in her review.