Current approaches for the treatment of multiple myeloma

Watanabe, Reiko; Tokuhira, Michihide; Kizaki, Masahiro

doi:10.1007/s12185-013-1294-z

Cited by 26 publications

(16 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In patients with relapsed disease, re-treatment with agents from the initial regimen may be considered in patients who achieved a partial response or better and a remission lasting 12 months or longer following initial treatment [91][92][93][94]. Patients who relapse rapidly following initial treatment should receive a different class of agents from their original treatment [95].…”

Section: Treatment Recommendationsmentioning

confidence: 99%

Clinical characteristics of patients with relapsed multiple myeloma

Dimopoulos

Terpos

Niesvizky

et al. 2015

Cancer Treatment Reviews

View full text Add to dashboard Cite

Although survival outcomes have improved over the last decade for patients with multiple myeloma (MM), few patients remain free of disease and most inevitably relapse. Selecting a treatment for patients with relapsed MM is challenging given the number and diversity of regimens patients may have previously received, which can affect subsequent therapeutic choices. Importantly, a number of patient- and disease-related factors can also have an effect on treatment choice, treatment efficacy, and tolerability; thus, an understanding of the heterogeneity of patients in the setting of relapsed MM is important for appropriate treatment selection. Here, we review select patient and disease characteristics reported in key interventional and observational studies in relapsed MM (including age, sex, race, and the presence of high-risk disease, renal impairment, or peripheral neuropathy at baseline) to examine common and disparate features of patients with relapsed MM. As therapeutic regimens can have varying efficacy and/or tolerability in patients depending on these factors, we also provide treatment recommendations for patients with select baseline characteristics.

show abstract

Section: Treatment Recommendationsmentioning

confidence: 99%

Clinical characteristics of patients with relapsed multiple myeloma

Dimopoulos

Terpos

Niesvizky

et al. 2015

Cancer Treatment Reviews

View full text Add to dashboard Cite

show abstract

“…Ikaros proteins in MM cells are targets of lenalidomide, a salidomide-like drug [66] that binds ubiquitin E3 ligase and alters its specificity, thereby promoting Ikaros protein degradation [64,65]. This suggests that in MM cells unlike B-ALL, the presence rather than the absence of Ikaros proteins promotes proliferation.…”

Section: Transcriptional Regulation Of the Ikaros Genementioning

confidence: 99%

Ikaros fingers on lymphocyte differentiation

Yoshida

Georgopoulos

2014

Int J Hematol

View full text Add to dashboard Cite

The Ikaros family of DNA binding proteins are critical regulators of lymphocyte differentiation. In multipotent hematopoietic progenitors, Ikaros supports transcriptional priming of genes promoting lymphocyte differentiation. Ikaros targets the Nucleosome Remodeling Deacetylase complex (NuRD) to lymphoid lineage genes, thereby increasing chromatin accessibility and transcriptional priming. After lymphoid lineage specification, Ikaros expression is raised to levels characteristic of intermediate B cell and T cell precursors, which is necessary to support maturation and prevent leukemogenesis. Loss of Ikaros in T cell precursors allows the NuRD complex to repress lymphocyte genes and extends its targeting to genes that support growth and proliferation, causing their activation and triggering a cascade of events that leads to leukemogenesis. Loss of Ikaros in B cell precursors blocks differentiation and perpetuates stromal adhesion by enhancing integrin signaling. The combination of integrin and cytokine signaling in Ikaros-deficient pre-B cells promotes their survival and self-renewal. The stages of lymphocyte differentiation that are highly dependent on Ikaros are underscored by changes in Ikaros transcription, supported by a complex network of stage-specific regulatory networks that converge upon the Ikzf1 locus. It is increasingly apparent that understanding the regulatory networks that operate upstream and downstream of Ikaros is critical not only for our understanding of normal lymphopoiesis, but also in placing the right finger on the mechanisms that support hematopoietic malignancies in mouse and human.

show abstract

“…Because high-dose chemotherapy with autohematopoietic stem cell transplantation, along with novel therapeutic agents, such as proteasome inhibitors and immunomodulatory drugs, increases response rates and extent of responses, the prognosis for MM patients has improved dramatically [1,2]. Nonetheless, most patients eventually relapse or develop progressive phases, which suggests the survival of malignant cells with proliferative capacity even after administration of those powerful regimens [3]. Improving treatment response and survival for MM patients requires evaluating and monitoring minimal residual disease (MRD) during treatment [4,5].…”

mentioning

confidence: 99%