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    Advancements in Follicular Lymphoma Driven by Converging Standards of Care and Novel Therapies

    In a recent OncLive® Scientific Interchange and Workshop, Christopher R. Flowers, MD, MS, from The University of Texas MD Anderson Cancer Center, discussed the current and emerging therapeutic advances in follicular lymphoma (FL). FL is a slow-growing type of non-Hodgkin lymphoma that presents several treatment challenges due to its indolent behavior and the varied responses patients have to different therapies.

    Dr. Flowers emphasized the need to identify optimal treatment sequencing and incorporate individual patient preferences in the management of FL. Despite patients often responding well to therapies, the disease eventually recurs, leading to the need for effective therapies beyond what they have previously received.

    Several promising treatment options have recently emerged, including bispecific antibodies and CAR T-cell therapies. However, the optimal sequencing of these agents for patients with relapsed/refractory FL is still unknown, particularly for older patients or those with health conditions that limit their ability to utilize these therapies effectively.

    Dr. Flowers discussed the phase 3 AUGMENT trial, which evaluated the combination of rituximab and lenalidomide compared to rituximab plus placebo in patients with indolent non-Hodgkin lymphoma. The study showed that the rituximab and lenalidomide combination prolonged progression-free survival and increased the complete response rate compared to rituximab plus placebo.

    The discussion also focused on the unmet need for biomarkers that can guide treatment decisions and watch-and-wait strategies in FL. Predictive biomarkers could help predict how patients will respond to different therapies and inform treatment sequencing to ensure the most effective and tolerable treatments are given.

    In the frontline setting, there are several therapeutic options available, including bendamustine plus rituximab, lenalidomide plus rituximab, and obinutuzumab-based regimens. The phase 3 RELEVANCE trial evaluated lenalidomide plus rituximab versus rituximab plus chemotherapy in patients with previously untreated, advanced FL. While the trial did not meet its primary endpoint, it demonstrated equivalent outcomes between the two treatment approaches.

    The panel of experts highlighted the importance of individualized treatment decisions based on patient and disease factors. Factors such as disease growth, tumor burden, and patient preferences play a significant role in choosing the appropriate therapy for each patient.

    Maintenance therapy after frontline treatment was also discussed, with experts expressing differing opinions on its use. Some believe that patients who achieve a partial response with their initial therapy may benefit from maintenance therapy, while others prioritize patient age and potential adverse effects when making maintenance therapy recommendations.

    In the second-line treatment setting, data from the phase 3 SYMPHONY-1 trial with the EZH2 inhibitor tazemetostat showed promising overall response rates in both EZH2-mutant and wild-type patients. The safety profile of tazemetostat was also discussed, with emphasis on its tolerability and ease of administration.

    Newer data from the phase 2 ROSEWOOD trial highlighted the efficacy of the BTK inhibitor zanubrutinib in patients with relapsed/refractory FL. The study showed that zanubrutinib had a higher overall response rate, complete response rate, and longer progression-free survival compared to obinutuzumab.

    Overall, the experts agreed that additional treatment options are needed in the second- and third-line settings before considering bispecific antibodies or CAR T-cell therapy. They emphasized the importance of individualized treatment approaches, taking into account patient preferences, disease factors, and potential adverse effects.

    In conclusion, while significant progress has been made in the treatment of follicular lymphoma, there are still unmet needs in identifying optimal treatment sequencing and incorporating individual patient preferences. Ongoing research and the development of predictive biomarkers may provide greater insights into personalized treatment approaches for this challenging disease.

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