Multiple myeloma is a hematologic malignancy characterized by plasma cell clonal expansion as well as end-organ damage due to increased levels of monoclonal proteins in both the plasma and urine. The clinical syndrome is characterized by hypercalcemia, renal insufficiency, anemia, and bone involvement that leads to pathologic fractures. This progressive disease can result in significant patient morbidity and mortality. Despite advances with treatment options and autologous stem cell transplantation, multiple myeloma remains incurable. Current front-line therapies include proteasome inhibitors, immunomodulators, anthracyclines, and steroids. Due to the advent of the immunomodulatory agents thalidomide and lenalidomide, as well as the proteasome inhibitor bortezomib, overall survival in patients with multiple myeloma has improved greatly. However, once patients progress through front-line therapy and have relapsed or refractory disease, treatment options have historically been very limited. Carfilzomib, a second-generation proteasome inhibitor, has shown impressive response rates as a single agent in the relapsed and refractory patient setting; this includes patients who are refractory to previous bortezomib therapy. In addition, a third-generation immunomodulator, pomalidomide, has also shown promising results in a similar patient population, including those patients who have been shown to be refractory to lenalidomide and bortezomib. Adverse effects of both of these medications have been considered tolerable in the relapsed or refractory population, especially considering the benefits that have been shown. Continuing clinical research will reveal the utility of these agents in combination regimens or in a front-line setting for patients with multiple myeloma.
Myelofibrosis is a BCR-ABL-negative myeloproliferative neoplasm characterized by abnormal hematopoiesis. Alterations to the Janus kinase-signal transducer and activator of transcription pathway result in dysregulation of gene transcription and cell proliferation. Patients with symptomatic myelofibrosis present with a variety of signs and symptoms including, but not limited to myelosuppression, marked splenomegaly, abdominal discomfort, fatigue, and blood transfusion-dependence. Traditional myelosuppressive therapies including hydroxyurea, azacitidine, and cladribine aim to reduce constitutional symptoms and control the burden of disease. Immunomodulators can potentially reverse anemia associated with myelofibrosis, but are poorly tolerated by most patients. The novel Janus kinase 2 (JAK2) inhibitor, ruxolitinib, has demonstrated marked improvements to constitutional symptoms and splenomegaly. While survival benefit has not yet been demonstrated, continued research into pharmacologic management of myelofibrosis offers the promise of altering the course of disease progression.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.