Involvement of the central nervous system (CNS) is a rare complication of multiple myeloma (MM). Herein, we have described the incidence, characteristics, prognostic factors for post CNS-MM survival, and outcome of CNS-MM and explored the efficacy of novel agents (NA) (thalidomide, bortezomib, lenalidomide) in this setting. Between 2000 and 2013, 31 (0.9 %) out of 3408 newly diagnosed symptomatic MM patients, consecutively diagnosed and treated during the same period in 12 Greek centers, developed CNS-MM (M/F 15/16, median age 59 years, range 20-96 years; newly diagnosed/relapsed-refractory 2/29; median time to CNS-MM diagnosis 29 months). Clinical and laboratory characteristics were retrospectively recorded. Twenty-six percent of patients had circulating plasma cells (PCs) or plasma cell leukemia (PCL) at CNS-MM and 39 % had skull-derived plasmacytomas, suggesting hematological and contiguous spread. Treatment for CNS-MM was offered in 29/31 patients and 11/29 responded (NA 18/29, additional radiotherapy 9/28, intrathecal chemotherapy 13/29). The median post CNS-MM survival was 3 months (95 % CI 1.9-4.1) and did not differ between patients treated with NA and/or radiotherapy vs. others. In the multivariate analysis, prior treatment of MM with NA, extramedullary disease (EMD) during MM course (i.e., plasmacytomas, circulating PCs, or documented PCL) and abnormally high LDH at MM diagnosis were independent prognostic factors, whereas treatment of CNS-MM with NA did not predict for post CNS-MM survival. Despite the relatively limited number of patients due to the rarity of CNS-MM, our results suggest that NA do not seem to improve post CNS-MM survival. Patients with EMD display shortened post CNS-MM survival and should be followed thoroughly.

Solitary plasmacytoma (SP) is a rare plasma cell dyscrasia characterized by the presence of bone or extramedullary plasma cell tumors. The treatment of choice is local radiotherapy (R/T) 6 surgical excision. The role of adjuvant chemotherapy (C/T) or novel agents (NA) is uncertain. Data related to prognostic factors are inconclusive. Herein, we describe the clinical features, survival and prognosis of 97 consecutive patients, 65 with bone SP (SBP), and 32 with extramedullary SP (SEP), diagnosed and treated in 12 Greek Myeloma Centers. Objective response rate (PR) and complete response (CR) was 91.8% and 61.9%, respectively, and did not differ between the 2 groups. Overall, 38 patients relapsed or progressed to multiple myeloma (MM). After a median follow-up of 60 months, 5 and 10-year overall survival (OS) probability was 92% and 89% in SEP and 86% and 69% in SBP, respectively (P 5 0.2). The 5-and 10-year MMfree survival (MMFS) probability was 90% and 70% for patients with SEP vs. 59% and 50% for patients with SBP, respectively (P 5 0.054). Overall, the 5-and 10-year OS probability, plasmacytoma relapse-free survival (PRFS), progression-free survival and MMFS was 84% and 78%, 72% and 58%, 58% and 43%, and 70% and 59%, respectively. In the multivariate analysis, prolonged PRFS and young age were positive predictors of OS. Achievement of CR was the only positive predictor of PRFS. Immunoparesis was the only negative predictor of progression to MM. The addition of C/T or NA-based treatment increased toxicity without offering any survival advantage over R/T.

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Multiple myeloma (MM) is associated with both cellular and humoral immune deficiencies and, despite significant advances in treatment, remains an incurable disease. Regulatory T-cells (Tregs) represent a critical subset of CD4 T-cells, characterized by CD4 + CD25+ Forkhead box P3+ (FoxP3+) phenotype, able to control peripheral tolerance and responses to foreign and tumor antigens. Tregs are elevated in various types of cancer, including hematological malignancies; in MM, data regarding Tregs function and numbers and their correlation with survival parameters are controversial. Advances in cancer biology have shown that the tumor microenvironment plays an important role in tumor progression. In MM, the highly immunosuppressive nature of the bone marrow microenvironment has been significantly elucidated in the past decade and it is now well acknowledged that targeting only the tumor clone may not be able to cure MM. Tregs within the tumor microenvironment might play a significant role in the suppression of antitumor immune responses against cancer cells and are considered to predict poor outcome in cancer patients; nonetheless the exact prognostic significance of this cell subpopulation in malignancies is still a matter of debate. In this review, we discuss the role of Tregs as an essential cell population of the MM immune microenvironment.