Corticosteroid-Refractory Myositis After Dual BRAF and MEK Inhibition in a Patient with BRAF V600E-Mutant Metastatic Intrahepatic Cholangiocarcinoma

Timothy P DiPeri; Mehmet Demirhan; Daniel D Karp; Siqing Fu; David S Hong; Vivek Subbiah; Joann Lim; Leomar Y Ballester; Jean H Tayar; Maria E Suarez-Almazor; Milind Javle; Funda Meric-Bernstam

doi:10.36401/JIPO-21-18

Corticosteroid-Refractory Myositis After Dual BRAF and MEK Inhibition in a Patient with BRAF V600E-Mutant Metastatic Intrahepatic Cholangiocarcinoma

J Immunother Precis Oncol. 2022 Feb 4;5(1):26-30. doi: 10.36401/JIPO-21-18. eCollection 2022 Feb.

Authors

Timothy P DiPeri¹, Mehmet Demirhan^{2

3}, Daniel D Karp², Siqing Fu², David S Hong², Vivek Subbiah², Joann Lim², Leomar Y Ballester^{4

5}, Jean H Tayar⁶, Maria E Suarez-Almazor^{6

7}, Milind Javle⁸, Funda Meric-Bernstam^{1

2

9}

Affiliations

¹ Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
² Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
³ Department of Medicine, Elmhurst Hospital Center, Icahn School of Medicine at Mount Sinai, New York City, NY, USA.
⁴ Department of Pathology and Laboratory Medicine, University of Texas Health Science Center, Houston, TX, USA.
⁵ Department of Neurosurgery, University of Texas Health Science Center, Houston, TX, USA.
⁶ Section of Rheumatology and Clinical Immunology, Department of General Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁷ Department of Health Services Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁸ Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁹ Department of Khalifa Institute for Personalized Cancer Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Abstract

Intrahepatic cholangiocarcinoma is a rare malignancy, which is rich in actionable alterations. Genomic aberrations in the mitogen-activated protein kinase (MAPK) pathway are common, and BRAF exon 15 p.V600E mutations are present in 5-7% of biliary tract cancers (BTC). Dual inhibition of BRAF and MEK has been established for BRAF-mutated melanoma and lung cancer, and recent basket trials have shown efficacy of this combination in BRAF V600E-mutant BTCs. Here, we report on a patient with BRAF exon 15 p.V600E mutant metastatic intrahepatic cholangiocarcinoma who was started on BRAF and MEK inhibition with vemurafenib and combimetinib. Shortly thereafter, he developed debilitating myositis, which was refractory to corticosteroids, requiring therapeutic plasma exchange and intravenous immunoglobulin. We also review BRAF as a target in BTCs, relevant clinical trials, and adverse events associated with BRAF and MEK inhibition.

Keywords: cholangiocarcinoma; myositis; precision oncology; targeted therapy.

Publication types

Case Reports

Grants and funding

Sources of Support: This work was supported in part by the following: National Institute of Health (NIH) Training of Academic Surgical Oncologists (5T32CA009599-32), Sheikh Khalifa Bin Zayed Al Nahyan institute for Personalized Cancer Therapy, NIH/NCATS Center for Clinical and Translational Sciences (CCTS)/MD Anderson Translational Informatics (UL1 TR003167), and National Cancer Institute (NCI) Cancer Center Support (CORE) Grant (5P30CA016672-44). The Targeted Agent and Profiling Utilization Registry (TAPUR) trial (NCT02693535) was sponsored by the American Society of Clinical Oncology (ASCO).