Different patterns of relapse after autologous peripheral blood stem cell transplantation in multiple myeloma: clinical results of 280 cases from the Spanish Registry

Abstract

BACKGROUND AND OBJECTIVES: Autologous peripheral blood stem cell (PBSC) transplantation is widely used to treat patients with multiple myeloma (MM). However, only a small fraction of patients remain free of disease in the long-term and most patients will finally relapse. The clinical presentation of relapse after transplantation is very heterogeneous and few reports have analyzed this situation. We report the clinical patterns of relapses after autologous transplantation of 280 patients with MM included in a Spanish Multicenter Registry. DESIGN AND METHODS: The medical records of 560 patients with MM transplanted in different centers in Spain, included in the Spanish Registry of Transplant in Multiple Myeloma, were reviewed. At diagnosis, 48 (8%) had stage I disease, 143 (25%) stage II and 369 (65%) stage III. The median time from diagnosis to transplantation was 13 months (4-143). The median age was 53 years (23-70). Of the 502 patients assessable for response to intensification therapy after transplantation, 241 (48%) achieved a complete response and 220 (43%) a partial response. The clinical characteristics of 280 patients (52%) who had relapsed after transplantation were retrospectively assessed during long-term post-transplantation follow-up. RESULTS: At a median follow-up of 23 months, 280(52%) patients had relapsed or progressed after transplantation. The median overall survival was 52 months (SE 8), (CI 95% 37-68) and median estimated progression-free survival was 33 months (SE 2.2, CI 95% 27-38). The median period for relapse was 30 months (2-84) with an actuarial risk of progression or relapse at 60 months after transplantation of 78%. The clinical patterns of relapse were very heterogeneous: 40 cases (14%) presented extramedullary manifestations with multiple plasmacytomas as the main symptoms of relapse, with a minimum or null monoclonal component (MC). In 51 cases (18%) only an insidious increase of MC protein in serum or urine was detected without other clinical manifestations. In 6 cases (2%) the relapse had criteria of plasmacytic leukemia. The remaining patients presented progressive increase of MC associated with plasmacytic bone marrow infiltration and different clinical myeloma symptoms, mainly new osteolytic lesions. The therapeutic approach was also very heterogeneous, with a global antitumoral response of 30%. Median overall survival after relapse was 14 months (SE 1.4) (CI 95% 11-17). INTERPRETATION AND CONCLUSIONS: The patterns of relapse of MM after high-dose therapy are very heterogeneous. The different clinical expressions of relapse may be due to clonal selection after high-dose therapy and could indicate the persistence of a resistant clone. Some patients relapse with extraosseous plasmacytomas without systemic disease. These findings suggest the need for an individualized approach during clinical follow-up after transplantation. Regarding treatment response, patients with myeloma who relapse after high-dose chemotherapy have been classically considered to have few therapeutic options. However, we observed that after different lines of treatment, at least one-third of patients responded, with a median overall survival, after relapse of 14 months. New drugs, such as thalidomide, have been recently proved to be effective in MM patients and could increase the response rate and survival of these patients.