Long-term efficacy of imatinib mesylate in patients with advanced Tenosynovial Giant Cell Tumor

F G M Verspoor,O Mir,W T A Van Der Graaf,M A J Van De Sande,A Italiano,J Desai,B M Seddon,H Gelderblom,J.-Y Blay,M J L Mastboom,S Stacchiotti,A Wagner,L Eberst,G Hannink,P A Cassier,M Brahmi,E Bompas,R G Maki

doi:10.1038/s41598-019-51211-y

Abstract

Tenosynovial giant cell tumors (TGCT), are rare colony stimulating factor-1(CSF-1)-driven proliferative disorders affecting joints. Diffuse-type TGCT often causes significant morbidity due to local recurrences necessitating multiple surgeries. Imatinib mesylate (IM) blocks the CSF-1 receptor. This study investigated the long term effects of IM in TGCT. We conducted an international multi-institutional retrospective study to assess the activity of IM: data was collected anonymously from individual patients with locally advanced, recurrent or metastatic TGCT. Sixty-two patients from 12 institutions across Europe, Australia and the United States were identified. Four patients with metastatic TGCT progressed rapidly on IM and were excluded for further analyses. Seventeen of 58 evaluable patients achieved complete response (CR) or partial response (PR). One- and five-year progression-free survival rates were 71% and 48%, respectively. Thirty-eight (66%) patients discontinued IM after a median of 7 (range 1–80) months. Reported adverse events in 45 (78%) patients were among other edema (48%) and fatigue (50%), mostly grade 1–2 (89%). Five patients experienced grade 3–4 toxicities. This study confirms, with additional follow-up, the efficacy of IM in TGCT. In responding cases we confirmed prolonged IM activity on TGCT symptoms even after discontinuation, but with high rates of treatment interruption and additional treatments.

Highlights

Surgical resection is the primary treatment for both subtypes
We have previously reported on the efficacy of Imatinib mesylate (IM) in Tenosynovial giant cell tumors (TGCT)
Five (11%) patients had grade 3–4 toxicities, including neutropenia, acute hepatitis, facial edema, skin toxicity and fatigue (Table 3). This retrospective study provides the largest case series, with long follow-up, of patients with locally advanced, recurrent or metastatic diffuse-type TGCT treated with IM

Summary

Introduction

Surgical resection is the primary treatment for both subtypes. diffuse TGCT is difficult to remove completely and often requires a total synovectomy, or at times a joint replacement, or rarely even amputation[1,2,7]. In patients with extensive and/or recurrent TGCT, other available treatment modalities include radiation. Synovectomy[8], external beam radiation therapy[9], and cryosurgery[10]. Their therapeutic value has only been assessed in retrospective, in most cases single center series and their long term side effects and complications are poorly described[11]. Inhibition of CSF1/CSF-1 receptor (CSF-1R) signaling has shown efficacy in the treatment of locally advanced and recurrent diffuse TGCT15–17. It has been shown that inhibition of CSF-1R by imatinib is competitive with ATP, with a Ki value of 120 nmol/L18. In the present study we provide long term follow-up on these initial patients and data on 33 additional consecutive patients

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Discussion

Conclusion