Near Complete Response to Trametinib Treatment in Histiocytic Sarcoma Harboring a Somatic KRAS Mutation

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  • 1 Division of Hematology/Hematologic Malignancies, Department of Internal Medicine, Huntsman Cancer Institute/University of Utah, Salt Lake City, Utah;
  • | 2 Division of Clinical Pathology, Department of Pathology, ARUP Laboratories and University of Utah, Salt Lake City, Utah;
  • | 3 Department of Radiation Oncology, and
  • | 4 Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, Huntsman Cancer Institute/University of Utah, Salt Lake City, Utah; and
  • | 5 Division of Hematology-Oncology, University of Alabama at Birmingham, Birmingham, Alabama.

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.

Submitted November 1, 2021; final revision received January 3, 2022; accepted for publication January 3, 2022. Published online March 24, 2022.

Disclosures: The authors have disclosed that they have no financial interests, arrangements, or affiliations with the manufacturers of any products discussed in this article or their competitors.

Funding: This work was supported by the Walter B. Frommeyer, Jr., Fellowship Award in Investigative Medicine, University of Alabama at Birmingham (G. Goyal).

Correspondence: Boyu Hu, MD, Huntsman Cancer Institute/University of Utah, 2000 Circle of Hope Drive, Research North – Room 2166, Salt Lake City, UT 84103. Email: boyu.hu@hci.utah.edu
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