0000000000064041
AUTHOR
Roman Hájek
Transcriptional profiling of circulating tumor cells in multiple myeloma: a new model to understand disease dissemination
The reason why a few myeloma cells egress from the bone marrow (BM) into peripheral blood (PB) remains unknown. Here, we investigated molecular hallmarks of circulating tumor cells (CTCs) to identify the events leading to myeloma trafficking into the bloodstream. After using next-generation flow to isolate matched CTCs and BM tumor cells from 32 patients, we found high correlation in gene expression at single-cell and bulk levels (r ≥ 0.94, P = 10−16), with only 55 genes differentially expressed between CTCs and BM tumor cells. CTCs overexpressed genes involved in inflammation, hypoxia, or epithelial–mesenchymal transition, whereas genes related with proliferation were downregulated in CTCs…
Longitudinal Immunogenomic Profiling of Tumor and Immune Cells for Minimally-Invasive Monitoring of Smoldering Multiple Myeloma (SMM): The Immunocell Study
Background: Although great strides were made in the management of MM, our best chances to eradicate this malignancy may lie in preventing its progression.Most current models to predict risk of transformation in SMM are commonly established at diagnosis and not reevaluated over time, because some parameters such as tumor burden or genetic abnormalities require invasive bone marrow (BM) aspirates. It could be hypothesized that periodic monitoring of tumor biomarkers is needed to improve risk-stratification of SMM patients, and so would be new minimally-invasive methods that can replace those performed in BM samples. Such methods should also monitor immune profiles, to identify patients with s…
Long-Term Outcomes and Health-Related Quality of Life (HRQoL) By Response Status for Bortezomib, Melphalan, and Prednisone (VMP) ± Daratumumab (DARA) in Alcyone
Introduction: DARA is a human IgGκ monoclonal antibody targeting CD38 with a direct on-tumor and immunomodulatory mechanism of action. In the phase 3 ALCYONE study (median follow-up of 40.1 months), DARA in combination with VMP (D-VMP) reduced the risk of disease progression or death by 58% versus VMP alone (median 36.4 vs 19.3 months; HR, 0.42; 95% CI, 0.34-0.51; P<0.0001) and demonstrated a significant overall survival (OS) benefit (median not reached in either group; HR, 0.60; 95% CI, 0.46-0.80; P=0.0003) for patients (pts) with transplant-ineligible newly diagnosed multiple myeloma (TIE NDMM). Here, we report the results of a subgroup analysis examining long-term efficacy outcome…
Superiority of the Triple Combination of Bortezomib-Thalidomide-Dexamethasone Over the Dual Combination of Thalidomide-Dexamethasone in Patients With Multiple Myeloma Progressing or Relapsing After Autologous Transplantation: The MMVAR/IFM 2005-04 Randomized Phase III Trial From the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation.
Purpose This prospective multicenter phase III study compared the efficacy and safety of a triple combination (bortezomib-thalidomide-dexamethasone [VTD]) versus a dual combination (thalidomide-dexamethasone [TD]) in patients with multiple myeloma (MM) progressing or relapsing after autologous stem-cell transplantation (ASCT). Patients and Methods Overall, 269 patients were randomly assigned to receive bortezomib (1.3 mg/m2 intravenous bolus) or no bortezomib for 1 year, in combination with thalidomide (200 mg per day orally) and dexamethasone (40 mg orally once a day on 4 days once every 3 weeks). Bortezomib was administered on days 1, 4, 8, and 11 with a 10-day rest period (day 12 to day …