Tenosynovial giant cell tumor: case report of a patient effectively treated with pexidartinib (PLX3397) and review of the literature

Abstract

BackgroundTenosynovial giant cell tumors (TGCTs) or giant cell tumors of tendon sheath are neoplasms that arise in the synovium. They can be categorized as nodular (localized) or diffuse type (D-TGCT). Historically, surgery has been the mainstay of therapy, but diffuse type disease recurs at a high rate and treatment often requires increasingly morbid procedures. Elucidation of the importance of the colony-stimulating factor (CSF1)/CSF1 receptor (CSF1R) pathway in the pathogenesis of this disease has created significant interest in targeting this pathway as a novel TGCT treatment approach. Pexidartinib, a selective tyrosine kinase inhibitor against CSF1R, showed an 83% disease control rate (52% with partial response and 31% with stable disease) in a recent phase 1 study of patients with TGCT.Case presentationWe present an illustrative example of a TGCT patient who would have required a morbid operation who derived considerable clinical benefit from pexidartinib treatment. Her tumor volume decreased by 48% after 4 months of treatment, and 55 months after starting treatment the patient exhibits continued disease stability with minimal clinical symptoms, and significant improvement in functional status.ConclusionsThis case illustrates the effectiveness of systemic therapy in controlling a disease associated with high surgical morbidity. This approach may be especially useful in the treatment of extra-articular disease which often invades neurovascular bundles; as the effectiveness in metastatic disease is still unknown. In the future, systemic treatment for TGCT may be appropriate for the neoadjuvant setting to decrease disease burden prior to surgery with the aim of decreasing recurrence rates. However, properly designed prospective studies will need to be carried out to answer these questions.

Pexidartinib: First Approval

“…Pexidartinib has been developed by Daiichi Sankyo for the treatment of tenosynovial giant cell tumor (TGCT; also known as giant cell tumor of the tendon sheath or pigmented villonodular synovitis [9]). Most commonly arising in the synovium of joints or tendon sheaths of young adults, TGCT is a rare and locally aggressive neoplasm that overexpresses CSF1 [10,11].…”

Pexidartinib (TURALIO™): The First FDA-Indicated Systemic Treatment for Tenosynovial Giant Cell Tumor

“…In contrast, diffuse TGCT (D-TGCT) is a more destructive and locally aggressive form of the disease in which the tumor infiltrates soft tissue mass along the synovial lining [ 6 , 7 ]. TGCT occurs primarily in young adults between 30 and 40 years of age [ 8 ]. The annual incidence of TGCT in the United States is approximately 11 cases per million people; of these, 9.2 cases are L-TGCT type and 1.8 cases are D-TGCT type [ 8 ].…”

“…TGCT occurs primarily in young adults between 30 and 40 years of age [ 8 ]. The annual incidence of TGCT in the United States is approximately 11 cases per million people; of these, 9.2 cases are L-TGCT type and 1.8 cases are D-TGCT type [ 8 ]. Although there is no sex predilection in the diffuse type, there is a higher prevalence of L-TGCT in females (1.6–2.1:1) [ 8 ].…”

“…Adequate surgical resection, when feasible, remains the treatment of choice for TGCT [ 9 ]. While localized disease is readily curable, diffuse disease has shown high recurrence rates with arthroscopy (40%) and open surgery (14%) [ 8 , 9 ]. Due to the high recurrence rates, patients will go through multiple surgical resections, which may reduce their quality of life, increase morbidity, and reduce the function of affected joints [ 5 ].…”

“…Since 2008, systemic treatment options for TGCT have been investigated but have been unsuccessful. Clinical activity was seen with monoclonal antibodies and tyrosine kinase inhibitors targeting the CSF1/CSF1 receptor (CSF1R) axis in patients with locally advanced or relapsed D-TGCT [ 8 , 9 ]. Intravenous monoclonal antibodies, emactuzumab and cabiralizumab, have been tested in patients with TGCT.…”