A randomized phase II, open-label and multicenter study of combination regimens of bortezomib at two doses by subcutaneous injection for newly diagnosed multiple myeloma patients

Li, Feng; Yao, Fusheng; Zhu, Xijun; Gu, Weiying; Wang, Xiaohua; Chen, Bing; Huang, Dong-Ping; Ding, Jia-Hua; Wu, Tian-Qin; Zhu, Yan; Zhao, Qian; Tang, Yong; Song, Peng; Zhao, Xiaogang; An, Zhi-Ming; Guo, Xing; Wang, Xu-Li; Zhong, Linhao; Xie, Xian-Jin; Zhai, Yong‐Ping

doi:10.1007/s00432-019-02967-3

Cited by 5 publications

(3 citation statements)

References 30 publications

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“…The median follow-up period was 25 months (IQR: 16–40). The median age at diagnosis was 57 years (IQR: 51–64), which was similar to other recent studies of Chinese MM patients ( 19 - 22 ). According to ISS, 57% (70/123) patients were at stage III.…”

Section: Resultssupporting

confidence: 88%

“…However, all the included patients were only bortezomib-based regimens, which could deduce the selection bias. Although similar with other recent studies of Chinese MM patients (19)(20)(21)(22), the median age at diagnosis was younger than Western people and few receive intensive treatment or ASCT dues to cost and acceptance of ASCT. Our results need to be verified by future studies.…”

Section: Discussionsupporting

confidence: 87%

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Partial immunoparesis contributes to risk of early infections in patients with multiple myeloma

Huang¹,

Wei²,

Wei³

et al. 2021

Transl Cancer Res TCR

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Background Partial immunoparesis, which means at least two suppressed uninvolved immunoglobulins (Igs), had been reported to be associated with poor prognosis in patients with multiple myeloma (MM), but the impact on early infections remains unknown. The purpose of our study was to determine the prognostic implications of partial immunoparesis on early grade ≥3 infections in patients with MM. Methods Herein we retrospectively analyzed the clinical data of 123 MM patients between 2012 and 2020 at Nanfang Hospital. All patients received bortezomib-based regimens. The relationship between early grade ≥3 infections and partial immunoparesis was investigated using Cox regression analysis. Results Our data showed partial immunoapresis was found in 63% MM patients. Partial immunoparesis was significantly related to elevated beta-2-microglobulin (B2M), decreased estimated glomerular filtration rate (eGFR) and progressive international staging system (ISS) stage (P<0.05). Especially, univariate Cox regression analysis showed partial immunoparesis was significantly correlated with early grade ≥3 infections (P=0.003). Moreover, multivariate Cox regression analysis showed partial immunoparesis was an independent significant prognostic factor for early grade ≥3 infections [odds ratio (OR) =3.048; 95% confidence interval (CI): 1.429–6.504; P=0.004]. Furthermore, partial immunoapresis could improve the infection risk model built by Dumontet et al. Conclusions Our study showed that partial immunoparesis could predict early infections in patients with MM, which may be used to identify the high risk patients for infections and guide strategies for infection prevention.

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Section: Resultssupporting

confidence: 88%

Section: Discussionsupporting

confidence: 87%

Partial immunoparesis contributes to risk of early infections in patients with multiple myeloma

Huang¹,

Wei²,

Wei³

et al. 2021

Transl Cancer Res TCR

View full text Add to dashboard Cite

show abstract

“…We next investigated whether SMAD1 expression is associated with response to standard MM treatment, containing BTZ and Dex [ 19 ]. In the APEX clinical trial, relapsed patients were treated with BTZ or Dex as a single agent.…”

Section: Resultsmentioning

confidence: 99%

SMAD1 as a biomarker and potential therapeutic target in drug-resistant multiple myeloma

Zhang

Faruq

et al. 2021

Biomark Res

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Background SMAD1, a central mediator in TGF-β signaling, is involved in a broad range of biological activities including cell growth, apoptosis, development and immune response, and is implicated in diverse type of malignancies. Whether SMAD1 plays an important role in multiple myeloma (MM) pathogenesis and can serve as a therapeutic target are largely unknown. Methods Myeloma cell lines and primary MM samples were used. Cell culture, cytotoxicity and apoptosis assay, siRNA transfection, Western blot, RT-PCR, Soft-agar colony formation, and migration assay, Chromatin immunoprecipitation (Chip), animal xenograft model studies and statistical analysis were applied in this study. Results We demonstrate that SMAD1 is highly expressed in myeloma cells of MM patients with advanced stages or relapsed disease, and is associated with significantly shorter progression-free and overall survivals. Mechanistically, we show that SMAD1 is required for TGFβ-mediated proliferation in MM via an ID1/p21/p27 pathway. TGF-β also enhanced TNFα-Induced protein 8 (TNFAIP8) expression and inhibited apoptosis through SMAD1-mediated induction of NF-κB1. Accordingly, depletion of SMAD1 led to downregulation of NF-κB1 and TNFAIP8, resulting in caspase-8-induced apoptosis. In turn, inhibition of NF-κB1 suppressed SMAD1 and ID1 expression uncovering an autoregulatory loop. Dorsomorphin (DM), a SMAD1 inhibitor, exerted a dose-dependent cytotoxic effect on drug-resistant MM cells with minimal cytotoxicity to normal hematopoietic cells, and further synergized with the proteasomal-inhibitor bortezomib to effectively kill drug-resistant MM cells in vitro and in a myeloma xenograft model. Conclusions This study identifies SMAD1 regulation of NF-κB1/TNFAIP8 and ID1-p21/p27 as critical axes of MM drug resistance and provides a potentially new therapeutic strategy to treat drug resistance MM through targeted inhibition of SMAD1.

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A systematic review on the epidemiology and treatment options of multiple Myeloma in Asia

Chng,

Nagarajan,

Huang

et al. 2024

Heliyon

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A randomized phase II, open-label and multicenter study of combination regimens of bortezomib at two doses by subcutaneous injection for newly diagnosed multiple myeloma patients

Cited by 5 publications

References 30 publications

Partial immunoparesis contributes to risk of early infections in patients with multiple myeloma

Partial immunoparesis contributes to risk of early infections in patients with multiple myeloma

SMAD1 as a biomarker and potential therapeutic target in drug-resistant multiple myeloma

A systematic review on the epidemiology and treatment options of multiple Myeloma in Asia

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