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Presenter: Mazyar Shadman

Mantle cell lymphoma remains incurable despite recent treatment advances, and most patients experience relapsed/refractory disease. BTK inhibitors are the preferred choice in the relapsed setting, especially in patients with early relapse. For patients with high-risk features such as TP53 mutation, early referral for CAR T-cell therapy should be considered, even in those with stable disease on a BTK inhibitor. Patients without high-risk features may be monitored and initiate CAR T-cell therapy after clinical disease progression. CAR T-cell therapy is an effective treatment with high rate of complete remissions. For patients who do not achieve a complete remission 3 months after CAR-T therapy, bridging therapy with chemotherapy or targeted therapy agents and referral for allogeneic transplant are recommended.

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Presenter: Jennifer A. Woyach

Minimal residual disease (MRD) in chronic lymphocytic leukemia (CLL) is defined as <1 CLL cell per 10,000 leukocytes (0.01%; <10−4). Flow cytometry and next-generation sequencing have demonstrated high sensitivity in MRD detection. MRD assessment may help to determine prognosis after fixed-duration regimens; this has been established in the contexts of chemoimmunotherapy and venetoclax/antibody combinations. In the short term, MRD status does not seem to inform prognosis in patients treated with a BTK inhibitor plus venetoclax-based regimens; however, long-term data will be needed to determine whether it is beneficial in this population. Numerous trials have demonstrated that MRD may be used to guide therapy. It is unclear whether using an MRD-guided treatment strategy is better than using fixed-duration therapy; ongoing and future studies are warranted.

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Presenter: Aaron T. Gerds

Mutations are a critical piece in understanding how myeloproliferative neoplasms (MPNs) occur, specifically the pathobiology of JAK/STAT activation. Mutations play such an important role, in fact, that they are a key part of the diagnostic classification for these diseases. Furthermore, the mutational landscape of MPNs affects both the prognosis and the biology of disease progression. Current research in the field is focused on understanding how and why these mutations occur, as well as how to attack them to address disease at the time of progression or even before disease progression has occurred.

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NCCN Guidelines® Insights: B-Cell Lymphomas, Version 5.2021

Featured Updates to the NCCN Guidelines

Andrew D. Zelenetz, Leo I. Gordon, Julie E. Chang, Beth Christian, Jeremy S. Abramson, Ranjana H. Advani, Nancy L. Bartlett, L. Elizabeth Budde, Paolo F. Caimi, Sven De Vos, Bhagirathbhai Dholaria, Bita Fakhri, Luis E. Fayad, Martha J. Glenn, Thomas M. Habermann, Francisco Hernandez-Ilizaliturri, Eric Hsi, Boyu Hu, Mark S. Kaminski, Christopher R. Kelsey, Nadia Khan, Susan Krivacic, Ann S. LaCasce, Megan Lim, Mayur Narkhede, Rachel Rabinovitch, Praveen Ramakrishnan, Erin Reid, Kenneth B. Roberts, Hayder Saeed, Stephen D. Smith, Jakub Svoboda, Lode J. Swinnen, Joseph Tuscano, Julie M. Vose, Mary A. Dwyer, and Hema Sundar

In the last decade, a better understanding of the molecular pathogenesis of B-cell non-Hodgkin lymphomas has resulted in the development of novel targeted therapies, such as small molecule inhibitors of select kinases in the B-cell receptor pathway, antibody–drug conjugates, and small molecules that target a variety of proteins (eg, CD-19, EZH2, and XPO-1–mediated nuclear export). Anti-CD19 CAR T-cell therapy, first approved for relapsed/refractory (R/R) diffuse large B-cell lymphoma, has also emerged as a novel treatment option for R/R follicular lymphoma and mantle cell lymphoma. These NCCN Guideline Insights highlight the new targeted therapy options included in the NCCN Guidelines for B-Cell Lymphomas for the treatment of R/R disease.

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Presenter: Shaji K. Kumar

The treatment of multiple myeloma (MM) has evolved over the past decade, yet it remains a chronic disease. Several trials of 4-drug induction regimens have resulted in deepening of disease response. With the emergence of multidrug regimens, questions have arisen regarding the role of autologous stem cell transplant (ASCT) in MM therapy and available treatment options after ASCT. Clinicians have also continued to improve the efficacy of maintenance therapies. In transplant-ineligible patients, the phases of treatment are less distinct; however, several regimens have demonstrated efficacy in this clinical setting. Future research should focus on individualizing treatment approaches.

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Presenter: Ranjana H. Advani

Goals of first-line therapy in classic Hodgkin lymphoma (cHL) should focus on balancing risk versus benefit to the individual while increasing efficacy and decreasing toxicity. Overall, the ABVD regimen is well tolerated but slightly less effective, with a better safety profile compared with escalated BEACOPP. BV-AVD is somewhere in between ABVD and escalated BEACOPP on the cure/morbidity scale. Interim PET is predictive, but new prognostic biomarkers are emerging that may better identify patients at high risk for treatment failure. In patients with interim PET-negative cHL, de-escalating therapy does not impact overall survival along 1) with no proven role for radiotherapy. cHL is largely a disease of young people, and the choice of treatment should always take into account the potential for both short- and long-term toxicity with the goal of optimizing survivorship.

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Presenter: Jennifer R. Brown

The choice of therapy for chronic lymphocytic leukemia (newly diagnosed as well as relapsed/refractory disease) depends on the disease (presence or absence of del(17p) or TP53 mutation) and patient characteristics (age, comorbidities, functional status and patient preference). Many patients can choose between continuous treatment with a Bruton’s tyrosine kinase (BTK) inhibitor or time-limited therapy with venetoclax/obinutuzumab. For patients with 17p deletions, the data support the use of continuous treatment with a BTK inhibitor, although these patients should also be referred to clinical trials evaluating novel combination therapy options with minimal residual disease monitoring. The choice of therapy for relapsed disease also depends on prior therapy and duration of response to prior therapy in addition to the disease and patient characteristics (as mentioned earlier). BTK inhibitor– or venetoclax-based regimens are recommended for patients experiencing relapse following chemoimmunotherapy. In the case of disease relapse following BTK inhibitor therapy, prospective data are available only for venetoclax-based regimens, whereas disease relapse (after a period of durable remission) following time-limited therapy with venetoclax-based regimens can be managed through re-treatment with venetoclax or a BTK inhibitor.

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Presenter: Ronald S. Go

The histiocytoses, a group of clonal and reactive conditions, arise from monocytic macrophage or dendritic cell lineages. The current NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Histiocytic Neoplasms reflect the most up-to-date, evidence-based data relating to the evaluation and management of this disease. Specifically, the guidelines focus on adult Langerhans cell histiocytosis, Erdheim-Chester disease, and Rosai-Dorfman disease. Because these disorders are rare, challenges have arisen regarding clinical suspicion, histologic diagnosis, treatment, and molecular subtyping. Future versions of the NCCN Guidelines will address the diagnosis and management of pediatric patients, as well as malignant histiocytosis.