Extramedullary progression of multiple myeloma despite concomitant medullary response to multiple combination therapies and autologous transplant: a case report

INTRODUCTION: Extramedullary myeloma that occurs during the clinical course of multiple myeloma is rare but is an independent poor prognostic factor with mortality of 73% and median survival of 12 months despite aggressive therapies including novel agents. The clinicopathological aspects, biology and management of extramedullary myelomas are poorly understood. Our case highlights the pathobiological aspects of this important but rare entity, and the repercussions of modern therapies. CASE PRESENTATION: A 60-year-old Caucasian man initially presented with an anterior rib fracture. Subsequent workup revealed stage IIIB immunoglobulin G lambda multiple myeloma. A bone marrow biopsy showed sheets of plasma cells, harboring unfavorable cytogenetics including deletion of 17p and t(4;14). He achieved near complete remission and resolution of karyotypic abnormalities with three cycles of induction doxorubicin, thalidomide, and dexamethasone (clinical trial). This was followed by high-dose melphalan and autologous stem cell transplant. He relapsed 1 year later. His bone marrow at that time showed only a few scattered polyclonal plasma cells. He received three cycles of bortezomib and tanespimycin (clinical trial) and achieved very good partial response. He again relapsed 1 year later with multiple large peripheral soft tissue masses and lymph nodes. Biopsies of the peripheral lesions were consistent with extramedullary myeloma, but repeat bone marrow biopsy continued to show no evidence of intramedullary disease. CONCLUSIONS: This is one of the few cases reported that illustrates the differential response of extramedullary compared to intramedullary myeloma to multiple standard combination therapies including novel therapeutics and transplant, resulting in a very short survival. Several mechanisms for intra-to-extra medullary migration and hence the differential treatment response have been hypothesized. Physicians should be aware of this problem during treatment with immunomodulatory drugs and proteasome inhibitors not only in relapsed but also in front-line setting. In such cases, there is a potential role for evolving targeted therapeutics as we continue to better understand the tumor biology.