Response to imatinib in villonodular pigmented synovitis (PVNS) resistant to nilotinib

Clinical Sarcoma Research

Paolo G Casali¹  Jean Y Blay⁴  Alessandro Gronchi⁵  Silvana Pilotti³  Antonella Messina⁶  Flavio Crippa²  Silvia Stacchiotti¹ 

[1] Adult Mesenchymal Tumor Medical Oncology Unit, Department of Cancer Medicine, Fondazione IRCCS Istituto Nazionale Tumori Milan, Milan, Italy;Department of Nuclear Medicine, Fondazione IRCCS Istituto Nazionale Tumori Milan, Milan, Italy;Department of Pathology and Molecular Biology, Fondazione IRCCS Istituto Nazionale Tumori Milan, Milan, Italy;Department of Medicine, Centre Léon Bérard, Lyon, France;Department of Surgery, Fondazione IRCCS Istituto Nazionale Tumori Milan, Milan, Italy;Department of Radiology, Fondazione IRCCS Istituto Nazionale Tumori Milan, Milan, Italy

关键词: Targeted therapy;    Imatinib;    PVNS;    Pigmented villonodular synovitis;   

Others  :  861445
DOI  :  10.1186/2045-3329-3-8

 received in 2013-03-04, accepted in 2013-05-07,  发布年份 2013

【 摘 要 】

Background

Pigmented villonodular synovitis (PVNS) is a rare locally aggressive tumor. PVNS is characterized in most cases by a specific t(1;2) translocation, which fuses the colony stimulating factor-1 (CSF1) gene to the collagen type VIa3 (COL6A3) promoter thus leading through a paracrine effect to the attraction of non-neoplastic inflammatory cells expressing CSF1-receptor. Imatinib is a tirosin-kinase inhibitors (TKI) active against CSF1-receptor whose activity in naïve PVNS was already described. We report on two PVNS patients who responded to imatinib after failure to nilotinib, another CSF1-receptor inhibitor.

Methods

Since August 2012, 2 patients with progressive, locally advanced PVNS resistant to nilotinib (Patient 1: man, 34 years; Patient 2: woman, 24 years) have been treated with second-line imatinib 400 mg/day. Both patients are evaluable for response.

Results

Both patients are still on treatment (7 and 4 months). Patient 1 had a dimensional response by MRI after 2 months from starting imatinib, together with symptomatic improvement. In Patient 2 a metabolic response was detected by [18F]fluorodeoxyglucose–positron emission tomography (PET) at 6 weeks coupled with tumor shrinkage by MRI, and symptomatic improvement.

Conclusions

Imatinib showed antitumor activity in 2 patients with nilotinib-resistant PVNS. This observation strengthen the idea that targeted agent with similar profile can give a different clinical result, as already described for gastrointestinal stromal tumor (GIST) patients treated with the same agents. Molecular studies are needed to clarify the biologic mechanism(s) underlying the response.

【 授权许可】

   
2013 Stacchiotti et al.; licensee BioMed Central Ltd.

【 图 表 】

【 参考文献 】

• [1]Mankin H, Trahan C, Hornicek F: Pigmented villonodular synovitis of joints. J Surg Oncol 2011, 103:386-389.
• [2]Blay JY, El Sayadi H, Thiesse P: Complete response to imatinib in relapsing pigmented villonodular synovitis/tenosynovial giant cell tumor (PVNS/TGCT). Ann Oncol 2008, 19:821-822.
• [3]Cassier PA, Gelderblom H, Stacchiotti S: Efficacy of imatinib mesylate for the treatment of locally advanced and/or metastatic tenosynovial giant cell tumor/pigmented villonodular synovitis. Cancer 2012, 118:1649-1655.
• [4]West RB, Rubin BP, Miller MA: A landscape effect in tenosynovial giant-cell tumor from activation of CSF1 expression by a translocation in a minority of tumor cells. Proc Natl Acad Sci USA 2006, 103:690-695.
• [5]Cupp JS, Miller MA, Montgomery KD: Translocation and expression of CSF1 in pigmented villonodular synovitis, tenosynovial giant cell tumor, rheumatoid arthritis and other reactive synovitides. Am J Surg Pathol 2007, 31:970-976.
• [6]Ray-Coquard I, Gelderblom H, Chevreau C: An open-label international multicentric phase II study of nilotinib in progressive pigmented villo-nodular synovitis (PVNS) not amenable to a conservative surgical treatment. J Clin Oncol 2012., 30(15 Suppl 1)
• [7]Brownlow N, Russell AE, Saravanapavan H: Comparison of nilotinib and imatinib inhibition of FMS receptor signaling, macrophage production and osteoclastogenesis. Leukemia 2008, 22:649-52.
• [8]Menetrier-Caux C, Montmain G, Dieu MC: Inhibition of the differentiation of dendritic cells from CD34(+) progenitors by tumor cells: role of interleukin-6 and macrophage colony-stimulating factor. Blood 1998, 92:4778-91.
• [9]Borg C, Terme M, Taïeb J: Novel mode of action of c-kit tyrosine kinase inhibitors leading to NK cell-dependent antitumor effects. J Clin Invest 2004, 114:379-88.
• [10]Ménard C, Blay JY, Borg C: Natural killer cell IFN-gamma levels predict long-term survival with imatinib mesylate therapy in gastrointestinal stromal tumor-bearing patients. Cancer Res 2009, 69:3563-9.
• [11]Zitvogel L, Kroemer G: Anticancer effect of imatinib via immunostimulation. Nat Med 2011, 17:1050-1.