Nathan H. Fowler - Follicular Lymphoma: Current Management and Novel Approaches

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Few things strike fear into the clinician and patient as the word cancer. Despite decades of research and countless dollars, the majority of cancers remain incurable, and therapy carries a high cost, both financially and on patients short- and long-term quality of life. With the exception of very early-stage malignancies, most cancers carry a high risk of relapse following frontline treatment. Side effects occur often, can be severe, and are unpredictable. Fortunately, due to technical advances, emerging science, and a fundamental shift in new drug development, we are witnessing dramatic improvements in life expectancy and treatment tolerability across a spectrum of malignancies.

For years, follicular lymphoma has remained a disease with more questions than answers. The natural history can be highly variable, and clinical information at diagnosis only occasionally predicts a patients long-term outcome. Some patients achieve spontaneous remission in the absence of therapy, while others transform or fail high-dose chemotherapy in short order. Historically, attempts to biologically define these dramatically different patient groups have been largely unsuccessful. Although the cell of origin and the hallmark mutation have been well described, very few targeted therapeutics existed. Finally, traditional chemotherapy approaches are associated with high response rates, yet nearly all patients still relapse. The reason behind many of these observations was largely unknown.

Fortunately, the last several years have been marked by a significant improvement in the understanding of the pathogenesis and biology underlying follicular lymphoma. Research into the role of the immune microenvironment have helped teams develop innovative approaches to treat follicular lymphoma. The work on key cellular pathways, novel cellular antigens, and unique genomic drivers has led to the identification of several potential therapeutic targets resulting in an explosion of active drugs and dramatically improved out-comes.

In this textbook, we will review the pathogenesis and molecular drivers of follicular lymphoma. We will also cover the history and activity of traditional therapeutic strategies and discuss many exciting advances which have recently become available for patients. In each section, the authors will also discuss the future therapeutic role of key molecular pathways, targeted agents, immunotherapeutics, and next-generation radiotherapy approaches.

As our understanding of lymphoma continues to evolve, I am confident that we will soon discover the answers to key questions surrounding follicular lymphoma. But most importantly, ongoing and future work will lead to even better options for clinicians eventually leading to curative, less toxic options for all patients.

Finally, whether clinician, scientist, patient, or caregiver, our time in this life is short. Never underestimate the power of small acts of kindness.