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Myeloma
Published in Kelechi Eseonu, Nicolas Beresford-Cleary, Spine Surgery Vivas for the FRCS (Tr & Orth), 2022
Kelechi Eseonu, Nicolas Beresford-Cleary
Current anti-myeloma regimens combine chemotherapy agents with steroids and either proteasome inhibitors or immunomodulatory drugs, with or without high-dose chemo-therapy and stem cell transplantation. High-dose steroids can reduce swelling and inflammation and provide rapid pain control and improvement, particularly in cases involving spinal cord compression.
Introduction to Cancer
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
The leukemias (a group of more than 100 diseases) are types of cancers affecting the blood cells or hemopoietic tissue. Strictly speaking, the term leukemia should only be used to refer to a cancer of the white blood cells (the leukocytes) but in practice tends to be applied to malignancies of any cellular element relating to the blood or bone marrow, including erythroid, lymphoid, or myeloid cells. Thus, in bone marrow cell cancer affecting the leukocytes, involvement of the myeloid cells is known as myeloma, and in multiple myeloma (the most common bone marrow cancer), a clone of plasma cells is involved. Similarly, red cell leukemia originating in the reticuloendothelial system is known as erythroleukemia, and cancer of the erythroid stem cells is known as primary polycythemia. In addition, all of these different cancer types may be described as chronic or acute. Lymphosarcoma is a cancer of the lymphoid cells, whereas Hodgkin’s disease is an example of a lymph adenoma that, although mainly affecting reticulum cells, can extend to eosinophils, fibroblasts, and lymphocytes.
External Control Using RWE and Historical Data in Clinical Development
Published in Harry Yang, Binbing Yu, Real-World Evidence in Drug Development and Evaluation, 2021
Qing Li, Guang Chen, Jianchang Lin, Andy Chi, Simon Davies
Multiple myeloma (MM) is a cancer that forms in a type of white blood cell called a plasma cell. The treatment of MM has changed during the last 10–15 years. With the development of the proteasome inhibitor Velcade® and the immunomodulatory agent Revlimid, Velcade®-dexamethasone (VD)-based and Revlimid-dexamethasone (RD)-based therapies have become the backbone of combination therapy (Rajkumar and Kumar 2016). When Velcade® was approved as a single-agent treatment for relapsed MM, the efficacy and safety profile of Velcade® was characterized in the phase III APEX study and in the phase III DOXIL-MMY-3001 study (Kane et al. 2006). As the other research progressed, results from several clinical trials suggested that adding dexamethasone to bortezomib can improve response rates in patients. The VD doublet regimen was widely used in routine clinical practice for relapsed MM patients in 2013. However, a direct comparison of VD versus Velcade® monotherapy was missing. Therefore, a meaningful cross-study comparison using different adequate arms to compare the VD doublet regimen versus Velcade® monotherapy was needed. The label expansion of Velcade® plus dexamethasone in patients with relapsed and/or progressive MM who have received at least one prior therapy was approved in the European Union (EU) in 2013 (European Medicines Agency [EMA] 2013, Dimopoulos et al. 2015). This approval was based on an integrated analysis that comprised three clinical trials: MMY-2045, APEX, and DOXIL-MMY-3001. The study information is summarized in Table 4.12.
Diagnosis for Chinese patients with light chain amyloidosis: a scoping review
Published in Annals of Medicine, 2023
Meilan Chen, Junru Liu, Xiaohong Wang, Xian Cao, Xin Gao, Lingjie Xu, Wang Liu, Jingnan Pi, Bin Wang, Juan Li
Congo red staining is the gold standard method for amyloid diagnosis and has been used for decades [73]. However, using Congo red also has several disadvantages. For instance, false-positive or false-negative results can occur due to inexperienced examiners [74]. In addition, the usual site of choice for biopsy is the involved organ. However, there are sometimes alternative sites chosen for biopsy due to the organ or technical limitations. In this study, we observed that the most biopsied sites in Chinese hospitals were for kidney, bone marrow, and skin/fat in that order, with varying favorable rates. In addition, we found that cardiac biopsy reports were rare, which may be due to the low acceptance of biopsy itself and the small number of healthcare providers with the relevant skills. Besides, we found that only 31.2% related patients were performed bone marrow biopsy. The reason may be due to the low percentage of bone marrow involvement and the percentage of myeloma plasma cells. Therefore, bone marrow biopsy may not be a good method for AL amyloidosis detection [75]. Hence, besides Congo Red staining, IF, IHC, electron microscope, mass spectrometry, and potassium permanganate staining are also recommended to improve the diagnostic accuracy of pathological examinations [29,36,76].
Antibody-drug conjugates for multiple myeloma
Published in Expert Opinion on Biological Therapy, 2021
Annabel McMillan, Dana Warcel, Rakesh Popat
Multiple myeloma (MM) is the second most common hematological malignancy with an incidence accounting for 2% of all cancers [1]. It is a disease infiltrating the bone marrow that may lead to skeletal lytic lesions (leading to fractures and bone deformities), renal impairment, recurrent infections (due to immune-paresis) and bone marrow failure [2]. Currently it is considered to be incurable; however, technological advances in drug development have led to the development of new treatments and significant improvements in overall survival. Currently, the median overall survival (OS) is in excess of 7 years [3]; however, for patients less than 50 years that are able to receive more intensive treatments such as autologous stem cell transplant, the median OS is over 10 years [4]. There are 5 main classes of myeloma treatments routinely used: proteasome inhibitors (PI), immunomodulatory agents (IMiDs), monoclonal antibodies (mAbs), alkylating agents and glucocorticoids [5]. As there are multiple sub-clones within MM, typically combinations of classes are used and given as continuous therapy.
A new decade: novel immunotherapies on the horizon for relapsed/refractory multiple myeloma
Published in Expert Review of Hematology, 2021
Marc Braunstein, Jonathan Weltz, Faith Davies
However, both laboratory and clinical data argue against this negative stance and actually suggest manipulating the immune system by both turning off inhibitory signals and turning on activating signals may be particularly effective in MM. For example, the use of allogeneic stem cell transplantation has been shown to partially restore immunesurveillance through a graft-versus-myeloma effect [9]. In addition, the immunomodulatory drugs (IMiDs), lenalidomide and pomalidomide have been shown to work at least in part via their effects on T cell and NK cell targeting of plasma cells [10,11], and preclinical data suggest that blockade of TGF-β can reinvigorate exhausted CD8+ T cell responses against MM plasma cells in the presence of immune checkpoint inhibitors that block the PD-L1 receptor, PD-1 [12].