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Boyu Hu, Jay L. Patel, Randa Tao, Richard B. Cannon, Marcus Monroe, and Gaurav Goyal

Survival outcomes of patients with histiocytic neoplasms are poor, with no standard-of-care treatments available for these malignancies. Recent characterization of the genomic landscape of various histiocytic neoplasms have shown a predominance of activating driver mutations within the MAPK/ERK pathway (ie, BRAF, MEK, KRAS, MAPK, and NRAS). Subsequently, successful treatment of these malignancies with BRAF and MEK inhibitors has been reported. This report presents the first patient with histiocytic sarcoma harboring a somatic KRAS Q61H mutation who was subsequently treated to a near complete response with the MEK inhibitor trametinib. Due to patient preference, lack of standard of care treatments, and associated morbidity from head and neck dissection, initial disease reduction provided by trametinib therapy allowed for a less morbid resection. This case report highlights the utility of up-front next-generation sequencing and the efficacy of MEK inhibition in patients with histiocytic sarcoma harboring activating KRAS mutations.

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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.