News in follicular lymphoma
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84
Follicular lymphoma (FL), the second most common lymphoma in Europe, represents a daily challenge for most hematologists, biologists, and pathologists. Recent years have seen several developments, from diagnosis to therapeutic strategies, indicating that we are reaching a major turning point. Here, we will discuss the more notable changes from recent years and future perspectives in FL. Regarding diagnostic criteria, the latest provisional World Health Organization classification of 2022 proposes some modifications including the removal of grading based on the centroblast count per high-power field for FL grades 1 to 3A. Grade 3B FL might be replaced by the term “large cell FL”. While some of these elements remain debated, their future adoption would require careful attention from all involved to eliminate any diagnostic ambiguity and ensure optimal care of FL patients. On the prognostic side, following the integration of positron emission tomography (PET scanning) in the initial evaluation, interest in osteo-medullary biopsy seems to be decreasing and is likely to lose its place in daily practice outside of clinical trials. Therapeutically, recent years have seen a decline in chemotherapy and confirmation of the value of immunotherapy and targeted therapies (i.e., lenalidomide, tazemetostat, and zanubrutinib.) While immunochemotherapy remains recommended in the first-line setting, the combination of anti-CD20 antibodies and lenalidomide has demonstrated non-inferiority in this indication and is establishing itself as a standard treatment in the second-line setting. Immediately after, in the third-line setting (for tisagenlecleucel) and fourth-line setting (for axicabtagene ciloleucel), chimeric antigen receptor T cells (CAR-T cells) are emerging as the primary option, with the development of lisocabtagene maraleucel showing impressive results in the second line of treatment. Among other options, bispecific anti-CD20-CD3 antibodies (mosunetuzumab, epcoritamab, and odronextamab) have shown exciting results in heavily pre-treated patients and will now be evaluated in clinical trials for first line patients suffering from FL with a high tumor mass, in combination with chemotherapy or lenalidomide.
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