Multiple myeloma with IGH-FGFR3 rearrangement progressing as testicular plasmacytoma during carfilzomib treatment

Abstract

Dear Editor, Multiple myeloma (MM) is a heterogeneous hematological malignancy with the clonal proliferation of plasma cells. Although MM remains incurable, treatment strategies have been improved by developing new agents and the overall survival of MM patients has significantly increased in the last decades [1]. Extramedullary spread of MM may occur either at diagnosis or during the disease course, and testis involvement is rare. We report an MM patient with IGH-FGFR3 rearrangement progressing as a testicular plasmacytoma during carfilzomib (CFZ) treatment. A 72-year-old man was diagnosed with MM with IGHFGFR3 rearrangement (IgG-λ, stage 2 according to the International Staging System [2]) 8 years ago. He received 3 cycles of bortezomib and dexamethasone induction therapy, and high-dose melphalan followed by autologous stem cell transplantation. He achieved very good partial response (VGPR) and was followed-up without any treatment. Four years later, he had significant paraprotein relapse without any other symptoms and received CFZ, lenalidomide, and dexamethasone (CLd) therapy. After 9 cycles of CLd therapy, he achieved VGPR again. After 1 year of CLd therapy, we stopped lenalidomide because of thrombocytopenia. Although he maintained VGPR for another year, he felt lefttesticular swelling and underwent left orchiectomy. Histopathology revealed infiltration of plasmacytoma in the testis, which was positive for IGH-FGFR3 by fluorescent in situ hybridization (FISH) analysis (Fig. 1). We confirmed the absence of M-protein in the serum and urine, and the percentage of plasma cells in the bone marrow was 0.2% and clonality of plasma cells was not detected. IGH-FGFR3 rearrangement was not detected in bone marrow by FISH analysis. There was no other plasmacytoma by FDG-PET/CT scan. Three months after the operation, disease progression was not observed and no additional treatment was given. Solitary extramedullary plasmacytomas are plasma cell tumors that arise outside of the bone marrow and are most often located in the head and neck region, mainly in the upper aerodigestive tract [3]. The incidence of solitary plasmacytoma during follow-up ofMM is 6% [4]. Testicular plasmacytomas are rare, accounting for only 1.3% of all extramedullary plasmacytomas [3] and 0.03 to 0.1% of all testicular tumors [5]. It is unclearwhether testicular involvement by plasmacytoma is associated with a risk of central nervous system relapse like diffuse large B cell lymphoma [6]. Although testicular plasmacytoma has been reported, the relationship with cytogenetic risk or new agents has not been reported. Cytogenetic abnormalities are powerful prognostic factors in MM [7]. Rearrangement of the FGFR3 and IGH genes is designated as t(4;14), and it has been observed in up to 15% of MM patients and is associated with poor prognosis [8]. Importantly, bortezomib improves the negative prognostic impact of t(4;14) [9]. Carfilzomib is an epoxyketone proteasome inhibitor that selectively and irreversibly binds the constitutive proteasome and immunoproteasome. The phase 3 study ASPIRE, which compared CLd with lenalidomide and dexamethasone (Ld), demonstrated CLd to have a favorable benefit-risk profile compared with Ld, regardless of baseline cytogenetic risk status, in patients with relapsed/refractory MM [10]. In our patient, CLd therapy was effective for MM with IgH-FGFR3 rearrangement and VGPR was maintained * Dai Maruyama [email protected]