Autologous stem cell transplant can overcome poor prognosis in patients with multiple myeloma with extramedullary plasmacytoma

Abstract

Multiple myeloma (MM) is a malignant condition of plasma cells, usually confi ned to the bone marrow. Under certain circumstances, extramedullary plasmacytomas (EMPs) may develop as a result of direct spread from the bone or hematogenous metastasis. About 7 – 18% of newly diagnosed myelomas are complicated by plasma cell tumors outside the bone marrow, with an additional incidence of EMP of 20% later during the course of the disease [1 – 4]. In spite of the increasing incidence of extramedullary disease, few studies have investigated the clinical features and prognosis of MM with EMP. Varettoni et al . [1], Wu et al . [2] and Usmani et al . [5] demonstrated that patients with MM without extramedullary involvement had better long-term outcomes than those with EMPs. However, these studies did not restrict the treatment strategy. Since transplant has become fi rst-line therapy for MM in patients younger than 65 years, the use of high-dose therapy (HDT) may be promising for patients with MM with EMP. Th erefore we conducted a retrospective analysis of patients with MM with EMP at the time of their initial diagnosis and investigated the eff ect of autologous stem cell transplant (ASCT) on their prognosis. One hundred and forty-nine patients with MM who underwent ASCT from 1 January 2005 to 31 December 2011 were included. Of these, 28 had confi rmed EMP when MM was initially diagnosed, which was defi ned as a mass of neoplastic monoclonal plasma cells in the soft tissue surrounding the bones or extraosseous organs, while solitary and bony plasmacytomas were excluded. Myeloma response and relapse before or after transplant were assessed based on the European Group for Blood and Marrow Transplantation (EBMT) criteria. Diff erences in continuous and dichotomous variables were tested by Student ’ s t -test and χ 2 test, respectively. Improvements of response status after ASCT were evaluated through the McNemar test. All tests were two-sided with p -values of less than 0.05 considered to be statistically signifi cant. Survival curves were plotted according to the method of Kaplan and Meier, and between-group comparisons of progression-free survival (PFS) and overall survival (OS) were done with the log-rank test. Prognostic factors for PFS and OS were analyzed by a Cox proportional hazards model. Twenty-eight of 149 patients had extramedullary involvement at the initial diagnosis of MM (median age 53.5 years, male/female 1:1). Table I outlines the clinical and laboratory features of patients with EMP. Soft tissue masses arising from the bone were most common (82.1%), including vertebrae (39.3%), rib (14.3%), clavicle (7.1%), inferior maxilla (7.1%), maxillae (3.6%), pelvis (3.6%), sternum (3.6%) and sternoclavicular joint (3.6%). Other locations with hematogenous spread included the pleura ( n 1), mediastinum ( n 1), liver ( n 2) and stomach ( n 1). Extramedullary involvement was found to be associated only with lower International Staging System (ISS) stage at the time of diagnosis of MM ( p 0.003). In the EMP group, most patients (71.4%) received a bortezomib-based regimen as induction chemotherapy. Sixteen (57.1%) patients in the EMP group and 82 (70.7%, response status of fi ve patients unknown) in the non-EMP group achieved at least a very good partial response (VGPR) ( p 0.168). EMP in 19 (67.9%) patients with MM disappeared after induction; 14 of them received bortezomib-based frontline therapy and the response rate of extramedullary disease to bortezomib-based therapy reached 70%. All patients underwent ASCT after induction chemotherapy with a conditioning regimen of melphalan alone or melphalan plus bortezomib. Ruling out the two patients with unknown response status, the two groups responded comparably well to HDT, with 46.6% complete response (CR), 35.7%