Bortezomib: a proteasome inhibitor for the treatment of autoimmune diseases

Khalesi, Naeemeh; Korani, Shahla; Korani, Mohsen; Johnston, Thomas P.; Sahebkar, Amirhossein

doi:10.1007/s10787-021-00863-2

Cited by 24 publications

(18 citation statements)

References 107 publications

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“…Proteasome inhibition in PCs causes accumulation of defective immunoglobulins and misfolded proteins, resulting in PC death (52-54). Proteosome inhibitors have been shown to ameliorate symptoms in patients with autoimmune diseases including SLE, RA, myasthenia gravis, neuromyelitis optica spectrum disorder, chronic inflammatory demyelinating polyneuropathy and autoimmune hematologic diseases that were unresponsive to conventional therapies (55).…”

Section: Discussionmentioning

confidence: 99%

Plasma cell but not CD20-mediated B-cell depletion protects from bleomycin-induced lung fibrosis

et al. 2022

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Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease associated with chronic inflammation and tissue remodelling leading to fibrosis, reduced pulmonary function, respiratory failure and death. Bleomycin (Blm)-induced lung fibrosis in mice replicates several clinical features of human IPF, including prominent lymphoid aggregates of predominantly B cells that accumulate in the lung adjacent to areas of active fibrosis. We have previously shown a requirement for B cells in the development of Blm-induced lung fibrosis in mice. To determine the therapeutic potential of inhibiting B cell function in pulmonary fibrosis, we examined the effects of anti-CD20 B-cell ablation therapy to selectively remove mature B cells from the immune system and inhibit Blm-induced lung fibrosis. Anti-CD20-B cell ablation did not reduce fibrosis in this model, however immune phenotyping of peripheral blood and lung resident cells revealed that anti-CD20 treated mice retained a high frequency of CD19+ CD138+ plasma cells (PCs). Interestingly, high levels of CD138+ cells were also identified in the lung tissue of patients with IPF, consistent with the mouse model. Treatment of mice with bortezomib, which depletes PCs, reduced the level of Blm-induced lung fibrosis, implicating PCs as important effector cells in the development and progression of pulmonary fibrosis.

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Section: Discussionmentioning

confidence: 99%

Plasma cell but not CD20-mediated B-cell depletion protects from bleomycin-induced lung fibrosis

et al. 2022

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“… 12 , 13 , 14 Bortezomib has been initially approved as the third‐line drug for relapsed and refractory MM treatment, and subsequently, as first‐line regent for mantle cell lymphoma and MM. 15 , 16 , 17 Bortezomib‐containing regimens such as VRd, bortezomib/cyclophosphamide/dexamethasone, 18 and bortezomib/melphalan/prednisone, 19 are considered as the standard first‐line therapeutic strategy for newly diagnosed MM. A phase II portion of the single‐arm study of VRd in newly diagnosed MM patients performed by Richardson et al demonstrated that 100% of ORR with 74% of VGPR or better was observed after 4 cycles of treatment.…”

Section: Discussionmentioning

confidence: 99%

“…[12][13][14] Bortezomib has been initially approved as the third-line drug for relapsed and refractory MM treatment, and subsequently, as first-line regent for mantle cell lymphoma and MM. [15][16][17] Bortezomib-containing regimens such as VRd, bortezomib/cyclophosphamide/dexamethasone, 18 and bortezomib/melphalan/prednisone, 19 of VGPR or better was achieved in newly diagnosed MM after four cycles of VRd treatment. 21 In our current study, after 4 cycles of VRd treatment in newly diagnosed MM patients, the ORR was 83.87% with 41.94% of VGPR or better, which was similar to that of Kumar's study.…”

Section: Discussionmentioning

confidence: 99%

Ixazomib combined with lenalidomide and dexamethasone chemotherapy for newly diagnosed multiple myeloma in China—Compared with bortezomib/lenalidomide/dexamethasone

et al. 2022

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Background To compare the response and safety of Ixazomib/Lenalidomide/Dexamethasone (IRd) and Bortezomib/Lenalidomide/Dexamethasone (VRd) treatment in newly diagnosed multiple myeloma (MM). Methods This was a single‐center retrospective analysis in Xiangtan Central Hospital. A total of 52 newly diagnosed MM patients from June 2019 to June 2021 were enrolled and divided into the IRd ( n = 21) and VRd ( n = 31) groups. After 4 cycles of chemotherapy, the best response and adverse events were recorded. Moreover, the progression‐free survival (PFS) and overall survival (OS) were calculated. Results Patients in IRd group and VRd group showed similar PFS (Log‐rank p = 0.70), OS (Log‐rank p = 0.61) and overall response rate (83.87% vs 90.48%, p = 0.803). In addition, patients in VRd group showed lower Eastern Cooperative Oncology Group scores ( p = 0.047), and higher incidence of peripheral sensory neuropathy (0.00% vs 19.35%, p = 0.032) than that of patients in IRd group. Conclusion Compared to VRd regimen, IRd had the similar efficacy, better safety, and may be more convenient for patients with poor basic condition for newly diagnosed MM. This study provides an insight for physicians to use IRd as first‐line treatment in MM.

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“…There was a growing number of new options for treatment of refractory MG, including neonatal Fc receptor blocking agents ( 37 ), Bortezomib [a proteasome inhibitor ( 38 )], tocilizumab [blocker of interleukin-6 ( 39 )], etc. However, few of them had been tested in trials of refractory MG. More well-designed clinical trials of these treatments on refractory MG and vigorous systemic reviews should be considered in order to establish an effective standardized treatment for patients with refractory MG.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Immunotherapies in Refractory Myasthenia Gravis: A Systematic Review and Meta-Analysis

Feng

Liu

et al. 2021

Front. Neurol.

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Introduction: Approximately 10–20% of patients WITH myasthenia gravis (MG) are refractory to conventional immunotherapies. The purpose of this study was to conduct a systematic review and meta-analysis to explore the optimal therapies for refractory MG.Method: Correlative studies were performed through a search in PubMed, Cochrane Library, and Embase databases. The primary outcome was defined by changes in the quantitative myasthenia gravis score (QMG). Secondary outcomes were defined by the Myasthenia Gravis Activities of Daily Living Scale (MG-ADL), Myasthenia Gravis Foundation of America (MGFA) post intervention status, adverse events, and disease exacerbation after treatment.Result: A total of 16 studies were included with 403 patients with refractory MG on therapies with rituximab, eculizumab, tacrolimus, and cladribine. Therapeutic efficacy of rituximab and eculizumab was identified with an estimated reduction in QMG score (4.158 vs. 6.928) and MG-ADL (4.400 vs. 4.344), respectively. No significant changes were revealed in efficacy or exacerbation density between the two independent therapeutic cohorts. The estimated adverse event density of eculizumab was more significant than that in the rituximab group (1.195 vs. 0.134 per patient-year), while the estimated serious event density was similar.Conclusion: The efficacy and safety of rituximab and eculizumab have been approved in patients with refractory MG. Rituximab had a superior safety profile than eculizumab with a lower incidence of adverse events.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021236818, identifier CRD42021236818.

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Bortezomib: a proteasome inhibitor for the treatment of autoimmune diseases

Cited by 24 publications

References 107 publications

Plasma cell but not CD20-mediated B-cell depletion protects from bleomycin-induced lung fibrosis

Plasma cell but not CD20-mediated B-cell depletion protects from bleomycin-induced lung fibrosis

Ixazomib combined with lenalidomide and dexamethasone chemotherapy for newly diagnosed multiple myeloma in China—Compared with bortezomib/lenalidomide/dexamethasone

Efficacy and Safety of Immunotherapies in Refractory Myasthenia Gravis: A Systematic Review and Meta-Analysis

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