Multiple myeloma is a malignant cancerous condition that is characterized by abnormal plasma cell production and can lead to bone destruction due to increased osteoclastic activity and decreased osteoblastic activity. Many therapeutic therapies are used to treat diseases, such as chemotherapy and radiotherapy. In recent years, anti-sclerostin antibody treatment has been under investigation for its effect on the multiple myeloma. The present study was conducted to assess the effective therapeutic use of anti-sclerostin antibody in the treatment of multiple myeloma. The literature search was conducted using PubMed, Google Scholar, ScienceDirect, and PubMed Central using the following MeSH terms: \"multiple myeloma\", \"anti-sclerostin antibody\", \"ubiquitin-proteasome pathway\", \"proteasome inhibitor\", \"Wnt pathway\". A total of 348 articles were screened. Twenty-five out of 348 were full-text articles assessed for eligibility, and four articles were used in this systematic review. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used for the reporting of this systematic review. A total of four randomized control trials (RCT) were included and used in this systematic review. The anti-sclerostin antibodies were various other drugs, and it was found that the anti-sclerostin antibody was effective in preventing autoantibody formation, decreasing bone destruction, and increasing trabecular bone. Anti-sclerostin antibody was found to be effective in decreasing bone destruction by reducing osteoclastic activity and increasing osteoblastic activity associated with multiple myeloma.

UNASSIGNED: Despite conspicuous advances in innovating novel drugs and combination regimens in multiple myeloma (MM) in recent decades, the most appropriate maintenance regimens after inductive therapy are still controversial and opaque.
UNASSIGNED: We aimed to identify the most effective maintenance treatment for newly diagnosed multiple myeloma (NDMM) patients via network meta-analysis.
UNASSIGNED: We searched PubMed, Embase, Cochrane Library, Scopus, and Google Scholars from inception to April, 2022. Odds ratios (ORs) were generated for dichotomous variants. The primary endpoint was overall survival (OS).
UNASSIGNED: Eventually a total of 19 trials, including 11 treatments and 8337 patients, were included in this analysis. For OS, lenalidomide (OR ranged from 1.61 to 1.99) and daratumumab (OR ranged from 1.83 to 2.41) showed significant efficacy over placebo. Maintenance therapy comprising lenalidomide-carfilzomib (OR ranged from 3.19 to 6.95), lenalidomide-prednisone (OR ranged from 2.62 to 4.44), bortezomib-thalidomide (OR ranged from 2.48 to 3.64), daratumumab (OR ranged from 2.0 to 2.98), lenalidomide (OR ranged from 1.4 to 3.19), ixazomib (OR ranged from 1.36 to 2.05), thalidomide (OR ranged from 1.5 to 1.86) demonstrated significant effects in prolonging PFS compared with placebo; Among the efficient therapies, lenalidomide-carfilzomib was significantly superior to lenalidomide (OR ranged from 2.18 to 2.20), daratumumab (OR ranged from 1.49 to 2.66) and ixazomib (OR ranged from 2.75 to 3.57).
UNASSIGNED: Considering OS and PFS, lenalidomide-carfilzomib should be recommended as the best therapy. In clinical practice, this must be weighed against the increased risk of adverse events and financial burden. However, more head-to-head studies are needed to confirm these findings.

Nocardia brain abscess is relatively rare, accounting for about 1-2% of all brain abscesses, and its mortality rate is three times higher than of other types of bacterial brain abscesses; thus, early diagnosis and treatment are essential. Nocardia brain abscess generally occurs in immunodeficient patients. We report a case of Nocardia farcinica brain abscess in a multiple myeloma patient treated with proteasome inhibitor (bortezomib and ixazomib), cyclophosphamide, and corticosteroid. The patient was treated with ceftriaxone and trimethoprim-sulfamethoxazole, together with drainage of the brain abscess. Regular brain MRI follow-ups showed that intracranial lesions were gradually absorbed and improved.

Lenalidomide use in nearly all induction regimens for multiple myeloma (MM) has led to the treatment of lenalidomide-refractory disease becoming one of the most important clinical questions in its treatment. Given the lack of direct comparisons of treatment regimens for lenalidomide-refractory MM, we used a systematic review to identify randomized controlled trials (RCTs) that included lenalidomide-refractory subgroup analysis.
We performed a systematic review to identify RCTs for MM that enrolled patients with lenalidomide-refractory disease, then performed a network meta-analysis (NMA) using random effects model to compare regimens.
We identified 123 discrete RCTs, of which 7 reported primary outcomes for lenalidomide-refractory MM. These were linked in 2 discrete networks totaling 1698 lenalidomide-refractory patients. Network 1 compared bortezomib (bort)/dexamethasone (dex) versus other treatments, and analysis showed triplet therapy with pomalidomide (pom)/bort/dex (hazard ratios [HR] 0.65, 95% confidence interval [CI], 0.50-0.84), daratumumab (dara)/bort/dex (HR 0.36, 95% CI, 0.21-0.63), and dara/carfilzomib (carf)/dex (HR 0.38, 95% CI, 0.21-0.69) as more effective than bort/dex. Network 2 compared dex versus other treatments, and analysis showed pom/dex (HR 0.50, 95% CI, 0.40-0.62), isatuximab (isa)/pom/dex (HR 0.30, 95% CI, 0.20-0.44), and elotuzumab (elo)/pom/dex (HR 0.27, 95% CI, 0.16-0.45) as more effective than dex. Within each network, monoclonal antibody (mAb)-containing regimens had lower HRs and higher P-scores than non-mAb regimens, indicating higher likelihood of these regimens being most efficacious.
The results of our NMA demonstrated that for lenalidomide-refractory MM, triplet therapy containing mAbs are superior. There is need for further RCTs to better ascertain the best standard of care for these patients.

Bortezomib is widely used in the treatment of Multiple Myeloma. While the most common side effects are neurological and gastrointestinal related complications, severe pulmonary problems are rarely described. The present case is a 72-year old male with multiple myeloma, who received Lenalidomide, Bortezomib, and Dexamethasone (RVD) combination regimen. He underwent 30 Gy palliative radiotherapy to the thoracic 5-9 and lumbar L1-3 vertebra due to pain and fracture risk. During the third cycle, he was admitted to hospital with dyspnea and dizziness. The thoracic CT revealed bilateral pleural effusions, a diffuse reticular pattern on the parenchyma, and ground-glass opacities that were compatible with drug-induced lung injury. The microbiological and molecular analysis excluded infectious disease, and lung biopsy confirmed the diagnosis of Bortezomib Lung Injury. The time from the first dose of Bortezomib to the lung injury was 57 days, and it was five days from the last dose of Bortezomib. His symptoms were refractory to IV steroids and supportive care. Our patient was lost despite steroids and intensive care support. Even Bortezomib induced lung injury is a rare adverse effect, based on high mortality rate, we would like to emphasize the clinical importance of this clinical scenario in light of the published literature and our presented case.

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BACKGROUND: Bortezomib is a reversible inhibitor of proteasome proteins in mammalian cells. Bortezomib is proven to be cytotoxic to a number of tumor cells by disrupting their normal homeostatic mechanism and thereby, causing cell death. Currently, Bortezomib is prescribed for patients with multiple myeloma and mantle cell lymphoma.
OBJECTIVE: This assessment highlights the overview of the recent patents of Bortezomib. This review includes patents grouped in sections like product patents, process patent, composition related patents as well as the treatment methodology. The objective of this article is to facilitate researchers with all existing patents at a single place.
METHODS: Data were searched from various online databases. In which, paid databases include SciFinder® and Orbit®. Free databases include Patentscope® (WIPO), Worldwide Espacenet® (EPO), Google Patents and InPASS (Indian patent database).
RESULTS: Several new processes and composition related patents of Bortezomib have been recently patented as its orange-book listed patents are going to soon expire during July 2022. Further, due to the problem of oxidation during development and long-term storage of Bortezomib formulation, a number of excipients are tried in these patents to stabilize the same. However, there is still a need for further development of an improved formulation of Bortezomib with better characteristics.
CONCLUSIONS: Extensive research has been carried out on various processes for preparing Bortezomib and the composition thereof. This type of dynamic research will clear the path for many generic players in the United States, which lead to the reduction of the price of the composition and thereby enhancing global health care at cheaper prices.

Standard induction therapy for multiple myeloma is three-drug combination based on following classes of drugs: proteasome inhibitors, immunomodulators and steroids. Despite its notable efficacy, bortezomib has side effects like peripheral neuropathy (PNP) with reported incidence of grade ≥3 PNP between 2%-23% Schlafer et al., 2017. Carfilzomib (CFZ) has high selectivity and minimal off-target adverse effects including lower rates of PNP. CFZ is already approved for treatment of relapsed and refractory multiple myeloma (RRMM) as single agent as well as in combination with lenalidomide and/or dexamethasone. Extensive literature search identified a total of 1839 articles. Twenty-six articles (n = 5980) met the inclusion criteria, 15 in newly diagnosed multiple myeloma (NDMM) and 11 in RRMM group. CFZ demonstrates comparable or even better efficacy to bortezomib with much favorable AE profile. Deep, rapid and sustainable response using KRd with safer toxicity profile supports extension of KRd therapy to frontline therapy for all risk categories of MM. High incidence of grade ≥3 HTN underscores the importance of serial BP monitoring. In RRMM, CFZ has documented efficacy with standard 20-27mg/m2 dose. Further large-scale trials are needed to study benefit-to-risk profile of 20-56 and 20-70 mg/m2 dose of CFZ vs standard 20-27 mg/m2 dose in NDMM and RRMM.

Organic anion transporting polypeptides (OATP) 1B1 and OATP1B3 are important hepatic transporters that mediate the uptake of many clinically important drugs, including statins from the blood into the liver. Reduced transport function of OATP1B1 and OATP1B3 can lead to clinically relevant drug-drug interactions (DDIs). Considering the importance of OATP1B1 and OATP1B3 in hepatic drug disposition, substantial efforts have been given on evaluating OATP1B1/1B3-mediated DDIs in order to avoid unwanted adverse effects of drugs that are OATP substrates due to their altered pharmacokinetics. Growing evidences suggest that the transport function of OATP1B1 and OATP1B3 can be regulated at various levels such as genetic variation, transcriptional and post-translational regulation. The present review summarizes the up to date information on the regulation of OATP1B1 and OATP1B3 transport function at different levels with a focus on potential impact on OATP-mediated DDIs.

Multiple myeloma (MM) accounts for 1.5% of all cancers and approximately 13% of all hematologic malignancies. Therapy for MM has substantially improved after the application of immunomodulatory drugs and proteasome inhibitors. The first proteasome inhibitor, bortezomib, can be considered a major milestone in treatment of MM, greatly improving the response rates and overall survival in front-line and relapsed/refractory settings. However, the prognosis of patients with progressive disease remains poor. In this article, we report a case of refractory MM patient who gained a long time disease control by bortezomib mono-therapy and do a critical review of the literature. We aim to share our experience of efficiency and safety of the long term mono-therapy of bortezomib in a refractory MM.