High-risk cytogenetic abnormalities (HRCAs) influence the prognosis of multiple myeloma (MM). However, additional cytogenetic aberrations can lead to poor outcomes. This study aimed to clarify whether HRCAs and additional chromosomal abnormalities affect MM prognosis. Patients with newly diagnosed MM who were treated with novel agents were retrospectively evaluated. The primary objective was to assess the difference in progression-free survival (PFS) and overall survival (OS) between patients with/without HRCAs and between patients with/without complex karyotype (CK). The secondary objectives were to identify factors affecting PFS/OS and factors related to CK. HRCAs were defined as del(17p), t(4;14), t(14;16), and gain/amplification(1q) assessed using fluorescence in situ hybridization. CK was defined as ≥3 chromosomal abnormalities on G-banding. Among 110 patients, 40 had HRCAs and 15 had CK. In this study, survival durations between patients with/without HRCAs were similar, while the CK group had significantly poorer PFS/OS than the no-CK group (median PFS: 9 vs. 24 months and median OS: 29 vs. 97 months, respectively), and a poor prognostic impact of CK was maintained in patients with HRCAs. In multivariate analysis, CK was correlated with poor PFS/OS (hazard ratio [HR]: 2.39, 95% confidence interval [95% CI]: 1.22-4.66 and HR: 2.66, 95% CI: 1.10-6.45, respectively). Bone marrow plasma cell (BMPC) ≥60% (odds ratio [OR] = 6.40, 95% CI: 1.50-27.2) and Revised International Staging System III (OR = 7.53, 95% CI: 2.09-27.1) were associated with CK. Our study suggests that CK may contribute to the poor prognosis of MM. Aggressive disease status including high BMPC proliferation could be relevant to CK.

OBJECTIVE: The current definition of complete remission (CR) in multiple myeloma (MM) includes negative serum and urine immunofixation (IFE) tests and <5% bone marrow plasma cells (BMPCs). The aim of this study was to examine the impact of BMPC percentage on survival, at diagnosis and pre-transplant period, in newly diagnosed multiple myeloma.
METHODS: One hundred and fourty eight patients with newly diagnosed MM who had received autologous stem cell transplantation (ASCT) in our HSCT (hematopoietic stem cell transplant) center at Hacettepe University Hospital between the years of 2008 and 2018 were evaluated retrospectively.
RESULTS: The median follow-up period was 27.4 months (range, 4.5-122) for the entire group. The 3-year OS was 87% in the pre-transplant BMPCs <5% group and 92% in the pre-transplant BMPCs ≥ 5% group, there was no statistically significant difference. The 5-year OS for the pre-transplant BMPCs <5% group and the pre-transplant BMPCs ≥ 5% group were 73% and 70%, respectively (p = 0.50). The 3-year PFS in the pre-transplant BMPCs <5% group and the pre-transplant BMPCs ≥ 5% group were 77% and 57%. The 5-year PFS in the pre-transplant BMPCs <5% group and the pre-transplant BMPCs ≥ 5% group were 43% and 13%, respectively. There was a statistically significant difference between the two groups with respect to PFS (p = 0.04).
CONCLUSIONS: In conclusion, this study highlights the importance of reaching <5% BMPCs at pre-transplant period. OS and PFS were better in patients who had pre-transplant BMPCs <5% than pre-transplant BMPCs ≥ 5%.

Vascular endothelial growth factor (VEGF) is pathognomonically elevated in patients with POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes) syndrome. However, its source of overproduction is unclear. As clinical improvement is almost always associated with VEGF reduction after anti-plasma cell therapy, its increase at diagnosis has been attributed to the underlying monoclonal gammopathy, although direct evidence is still lacking. In the current study, we systemically measured VEGF levels in POEMS patients, before and after treatment. Bone marrow plasma cells showed remarkable VEGF expression, in both mRNA and protein levels, which decreased gradually in response to therapy. Of note, statistically linear correlations were observed between serum and bone marrow plasma cell VEGF levels (mRNA vs. serum, rho 0.343, p=0.003; protein vs. serum, rho 0.644, p<0.0001), supporting bone marrow plasma cells as the main source of circulating VEGF. Intriguingly, immunophenotyping revealed that bone marrow plasma cells were polyclonal in most patients at diagnosis. A clear monoclonal population, coexistent with polytypic cells, was only detectable in 11 cases (18%), in which comparable intracellular VEGF expression was observed between these two plasma cell populations (p=0.594), while monoclonal cells showed higher intracellular interleukin-6 expression (p=0.006). These patients had more serum monoclonal protein, less post-therapeutic complete remission, and inferior overall (p=0.027) and progression-free survival (p=0.002). Collectively, bone marrow plasma cells, mainly polyclonal population, are the major source of VEGF overproduction in POEMS patients.