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Patients ≥ 80 years of age present with features of advanced myeloma and impaired performance status. The addition of novel agents may improve their outcome, but careful assessment and prospective clinical trials targeting the population of elderly patients are needed.

The aim of the study was the evaluation of anti-angiogenic activity of the combination of intermediate doses of thalidomide and dexamethasone in patients with refractory/relapsed myeloma. Twenty-five patients were included in the study. Microvessel density (MVD) was evaluated in marrow biopsies before and after treatment. Serum levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (b-FGF), tumor necrosis factor-alpha (TNF-alpha), which have angiogenic potential and interleukin-6 (IL-6), IL-1beta, soluble IL-6 receptor (sIL-6R), and transforming growth factor-beta (TGF-beta) which are involved in the disease biology, were measured before treatment and then every 2 weeks for 8 weeks. Pretreatment levels of MVD, VEGF, b-FGF, IL-6, sIL-6R were increased in the patients compared to controls. The overall response rate to therapy was 72%. The administration of the combined regimen produced a significant reduction in MVD in responders. However, an increase in serum levels of VEGF, b-FGF, IL-6, sIL-6R was observed post-treatment in responders. In contrast, serum levels of TNF-alpha, TGF-beta, IL-1beta did not differ between patients and controls and remained unchanged during the study. These results suggest that the combination of thalidomide plus dexamethasone is an effective treatment for myeloma reducing MVD marrow levels but not serum levels of angiogenic cytokines or cytokines implicated in myeloma biology.

predicting OS were blast count (p < .001), white blood cells (p = .009), TET2 (HR .54, p < .001), IDH2 (HR .5, p = .021), NRAS (HR 2.23, P = .017) mutation. Notably, fibrosis, cytogenetics, WHO categories were not associated with different survival in MVA. Summary/Conclusion:In conclusion, SRSF2-mutated myeloid neoplasms are a subset of myeloid neoplasms characterized by bone marrow dysplasia and overall dismal prognosis, whose fibrotic or proliferative phenotype results from a restricted co-mutation pattern. Among MPN, SRSF2 mutation is almost invariably associated with MF, further supporting the concept that PMF is an MDS/MPN disorder. Co-mutational pattern is the best predictor of clinical phenotype, suggesting that recognition of a distinct entity with a unique molecular basis may significantly improve classification and treatment of patients with these disorders.

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