RESEARCH REPORT Leah Lawrence A majority of patients with multiple myeloma are being treated with novel agents such as thalidomide, bortezomib, and lenalidomide within a year of diagnosis instead of the chemotherapeutic regimens that were more prevalent a decade ago, according to a new study.
PODCAST Kenneth Anderson, MD In this interview we discuss the current management and latest treatments and agents in development for multiple myeloma with Dr. Kenneth Anderson of the Dana-Farber Cancer Institute.
CONFERENCE REPORT Cancer Network presents exclusive coverage from the American Society of Hematology (ASH) annual meeting. We'll bring you onsite reports as we cover the latest research, trials, scientific advances, and controversies that are changing the way hematologic malignancies are managed and treated.
Multiparameter flow cytometry and deep sequencing were both able to accurately identify patients with multiple myeloma who were negative for minimal residual disease, a factor that was found to better predict prolonged survival compared with complete response as measured by traditional response criteria.
Pomalidomide in combination with low-dose dexamethasone had a highly significant benefit on progression-free survival and overall survival compared with single-agent high-dose dexamethasone in patients with relapsed or refractory multiple myeloma, according to updated results of the MM-03 trial presented at the ASCO 2013 Annual Meeting.
A majority of patients with multiple myeloma are being treated with novel agents such as thalidomide, bortezomib, and lenalidomide within a year of diagnosis instead of the chemotherapeutic regimens that were more prevalent a decade ago, according to a new study.
African American men with multiple myeloma had a significantly lower frequency of IgH translocations, a signal of nonhyperdiploid multiple myeloma, compared with European American men, according to the results of a new study published in Blood.
ARRY-520, a novel selective kinesin spindle protein (KSP) inhibitor showed promising clinical activity both alone and combined with low-dose dexamethasone in a phase II clinical trial in patients with relapsed and refractory multiple myeloma.
Preliminary findings presented at ASH suggest a “favorable emerging clinical profile” for once weekly administration of MLN9708 in combination with lenalidomide and dexamethasone in patients with newly diagnosed multiple myeloma.
Data from an on-going early stage phase I/II trial of daratumumab in multiple myeloma continues to show promising activity. The dose-escalation study has shown that higher doses of daratumumab alone can reduce both bone marrow plasma cells as well as paraprotein.
Wogonin is one of the major constituents derived from Scutellaria Baicalensis, which has been reported to inhibit cell growth and/or induce apoptosis in various cancer cell lines. We aim to investigate the anticancer effects and associated mechanisms of wogonin on human multiplemyeloma cell line in vitro.|Effects of wogonin on the proliferation, cell cycle progression, and apoptosis of human myeloma cells were examined in vitro. The proteins associated with the biological effects of wogonin were analyzed by immunoblotting and immunocytochemical staining. In addition, the binding mode of wogonin within crystal structure of Akt1 protein was also evaluated by molecular docking analysis using the CDOCKER algorithm in Discovery Studio.|Myeloma cell growth was attenuated by wogonin (70.4-352.0 M) in a concentration-dependent manner. Cell cycle progression analysis and TUNEL assay showed that apoptosis was enhanced in wogonin-treated cells. Increased apoptosis was accompanied by decreased
Newer systemic therapies have significantly advanced the treatment of multiplemyeloma, but additional agents are needed. Bortezomib is a proteasome inhibitor with efficacy in relapsed/refractory multiplemyeloma that inhibits tumor angiogenesis, a process that has been implicated in multiplemyeloma pathogenesis.|In AMBER("A Randomized, Blinded, Placebo-Controlled, Multicenter, Phase II Study of Bevacizumab in Combination With Bortezomib in Patients With Relapsed or Refractory MultipleMyeloma"), patients with relapsed or refractory multiplemyeloma were randomized to receive bortezomib (1.3 mg/m(2) on days 1, 4, 8, and 11 of each 21-day cycle) and either placebo or bevacizumab (15 mg/kg on day 1 of each cycle) for up to 8 cycles. At completion, patients in the bortezomib-plus-bevacizumab arm could continue bevacizumab until they developed progressive disease or unacceptable toxicity. The primary endpoint was progression-free survival (PFS).|The stratified hazard ratio of PFS for the
Recently, we showed that increased miR-181a expression was associated with improved outcomes in cytogenetically normal acute myeloid leukemia (CN-AML). Interestingly, miR-181a expression was increased in CN-AML patients harboring CEBPA mutations, which are usually biallelic and associate with better prognosis. CEBPA encodes the C/EBP transcription factor. We demonstrate here that the presence of N-terminal CEBPA mutations and miR-181a expression are linked. Indeed, the truncated C/EBP-p30 isoform, which is produced from the N-terminal mutant CEBPA gene or from the differential translation of wild-type CEBPA mRNA and is commonly believed to have no transactivation activity, binds to the miR-181a-1 promoter and up-regulates the microRNA expression. Furthermore, we show that lenalidomide, a drug approved for myelodysplastic syndromes and multiplemyeloma, enhances translation of the C/EBP-p30 isoform, resulting in higher miR-181a levels. In xenograft mouse models, ectopic miR-181a
We conducted a retrospective study to compare thalidomide, bortezomib and dexamethasone (VTD) with thalidomide plus doxorubicin and dexamethasone (TAD). Until now, first-line treatment with these combinations has not been reported in any comparative study. The principal objective of this study was to determine whether VTD would improve the complete response (CR) and CR plus very good partial response rates compared with TAD. Second, using additional methods, such as flow cytometric assays and polymerase chain reaction technology, we evaluated the molecular residual disease in the subgroup of patients that obtained CR. Our study shows that VTD is a superior induction regimen compared with TAD, with a higher response rate after induction, translating into greater CR plus very good partial response.
The Tel2 (also known as Telo2) and Tti1 proteins control the cellular abundance of mammalian PIKKs and are integral components of mTORC1 and mTORC2. Here we report that Tel2 and Tti1 are targeted for degradation within mTORC1 by the SCFFbxo9 ubiquitin ligase to adjust mTOR signalling to growth factor availability. This process is primed by CK2, which translocates to the cytoplasm to mediate mTORC1-specific phosphorylation of Tel2/Tti1, subsequent to growth factor deprivation. As a consequence, mTORC1 is inactivated to restrain cell growth and protein translation whereas relief of feedback inhibition activates the PI(3)K/TORC2/Akt pathway to sustain survival. Significantly, primary human multiple myelomas exhibit high levels of Fbxo9. In this setting, PI(3)K/TORC2/Akt signalling and survival of multiplemyeloma cells is dependent on Fbxo9 expression. Thus, mTORC1-specific degradation of the Tel2 and Tti1 proteins represents a central mTOR regulatory mechanism with implications in