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Interferon-alpha in the treatment of multiple myeloma.

Interferons are soluble proteins produced naturally by cells in response to viruses. It has both anti-proliferative and immunomodulating properties and is one of the first examples of a biological response modifier use to treat the haematological malignancy multiple myeloma. Interferon has been used in this clinical practice for over thirty years. However, despite considerable efforts, numerous clinical trials and two large meta-analysis, its exact role in the management of multiple myeloma still remains unclear. Its role in the treatment of multiple myeloma has been as a single induction agen…

Current diagnosis and management of multiple myeloma.

The availability of a wide variety of treatments for multiple myeloma allows healthcare providers to tailor treatments to individual patient needs, and has enabled prolonged survival of patients with the disease. Improved understanding of the disease, its treatment options, and potential side effects of therapy has provided unique opportunities for oncology nurses to employ preventive approaches, care strategies, and patient and family education and support over time. Because therapies have been developed that prolong the survival time, people with multiple myeloma are in the position of livin…

Epigenetic silencing of MIR203 in multiple myeloma.

Epigenetic inactivation of tumour suppressor microRNAs has been implicated in carcinogenesis. We studied the promoter methylation of MIR203 in eight normal marrow controls, eight multiple myeloma (MM) cell lines, 20 monoclonal gammopathy of undetermined significance (MGUS), 123 diagnostic MM and 19 relapsed MM samples by methylation-specific polymerase chain reaction. Promoter of MIR203 was unmethylated in normal controls but homozygously methylated in 25% MM cell lines. Treatment with 5-Aza-2'-deoxycytidine led to promoter demethylation and MIR203 re-expression. Cyclic AMP responsive element …

The DAC system and associations with multiple myeloma.

Despite the clear progress achieved in recent years in the treatment of MM, most patients eventually relapse and therefore novel therapeutic options are still necessary for these patients. In this regard, several drugs that target specific mechanisms of the tumor cells are currently being explored in the preclinical and clinical setting. This manuscripts offers a review of the rationale and current status of the antimyeloma activity of one of the most relevant examples of these targeted drugs: deacetylase inhibitors (DACi). Several studies have demonstrated the prooncogenic activity of deacety

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… Kyle RA Rajkumar SV Multiple myeloma N Engl J Med 2004 351 1860 1873 10.1056/NEJMra041875 15509819 2. … Bortezomib in patients with relapsed multiple myeloma ASH Annu Meet Abstr 2009 114 3852- 84. …

Recent advances in the management of multiple myeloma.

Multiple myeloma is a disease of malignant plasma cells in the bone marrow. Interaction of malignant plasma cells with the bone marrow microenvironment plays a key role in the pathogenesis of the disease. The Introduction of two new classes of molecules, namely immunomodulators (e.g. thalidomide, lenalidomide), and proteasome inhibitors (e.g., bortezomib) has led to improvement in the management of myeloma. Induction therapy with these novel drugs in combination with dexamethasone is associated with higher response rates including complete response in one-fourth of patients with bortezomib com…

MYEOV is a prognostic factor in multiple myeloma.

OBJECTIVE: Multiple myeloma is a plasma cell neoplasm characterized by the accumulation of malignant plasma cells within the bone marrow. This disease remains incurable despite major treatment improvements. However, gene expression profiling of multiple myeloma cells (MMC) may lead to identification of new therapeutic targets. MATERIALS AND METHODS: Using Affymetrix microarrays, we identified the overexpression of the MYEOV gene in MMC of 171 patients with newly diagnosed multiple myeloma compared to normal plasma cells. RESULTS: The MYEOV gene was present (Affymetrix call) in 79% of MMC and…

Infection and killing of multiple myeloma by adenoviruses.

Oncolytic virotherapy makes use of the natural ability of viruses to infect and kill cancer cells. Adenovirus serotype 5 (Ad5) has been approved for use in humans as a therapy for solid cancers. In this study, we have tested whether Ad5 and low-seroprevalence adenoviruses can be used as oncolytics for multiple myeloma (MM). We show that Ad5 productively infects most myeloma cell lines, replicates to various degrees, and mediates oncolytic cell killing in vitro and in vivo. Comparison of Ad5 with low-seroprevalence Ads on primary marrow samples from MM patients revealed striking differences in …

Bortezomib for the treatment of multiple myeloma patients.

This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of bortezomib for the treatment of multiple myeloma patients at first relapse and beyond, in accordance with the licensed indication, based upon the evidence submission from Ortho Biotech to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The outcomes stated in the manufacturer's definition of the decision problem were time to disease progression, response rate, survival and quality of life. The…

Treatment of multiple myeloma: a comprehensive review.

Multiple myeloma (MM) is a neoplastic plasma cell disorder that results in end-organ damage (hypercalcemia, renal insufficiency, anemia, or skeletal lesions). Patients should not be treated unless they have symptomatic (end-organ damage) MM. They should be classified as having high-risk or standard-risk disease. Patients are classified as high risk in the presence of hypodiploidy or deletion of chromosome 13 (del[13]) with conventional cytogenetics, the presence of t(4:14), t(14;16), t(14;20) translocations or del(17p) with fluorescence in situ hybridization. High-risk disease accounts for abo…

Managing anemia in lymphoma and multiple myeloma.

Anemia is common in cancer, and lymphoproliferative disease is no exception. Erythropoiesis-stimulating agents (ESA) have been used for renal anemia since 1986, and considerably later in cancer anemia. The first studies were published around 1993, but the use of ESA did not become common in cancer anemia until in the late 1990s. Cancer anemia is still under-treated. This review gives an overview of the use of ESA in hematologic malignancies. A background is given about this treatment in the cancer field generally. The pathophysiology of cancer anemia is described with special emphasis on the d

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… In general, anemia is common in lymphoproliferative disorders (lymphoma and multiple myeloma). Kyle (1975) reported Hb < 12 g/dl in 73% of newly diagnosed myeloma patients and Moullet and colleagues (1998) found Hb < 11 g/dl in 32% of newly diagnosed non-Hodgkin’s lymphoma patients. … Anemia treatment in lymphoproliferative disease The anemia problem in lymphoma and multiple myeloma is greater than in many other cancer forms ( Birgegård et al 2006 ). …

Current and emerging treatments for multiple myeloma.

BackgroundThe prognosis and treatment of multiple myeloma (MM) has evolved greatly over the past decade. The development and incorporation of new agents such as immunomodulators and proteasome inhibitors into therapy has improved outcomes and is helping patients enjoy longer periods of remission.ObjectiveTo review current treatments for MM, including overview of drug therapy and management of adverse effects of therapy and comorbidities. Additionally, an overview of agents being studied and evaluated for use in MM and myeloma-related conditions, such as metastatic bone disease and venous throm…

Lenalidomide in the treatment of multiple myeloma: a review.

Lenalidomide is an immunomodulatory drug derived from thalidomide. It was developed to maximize the anti-inflammatory and anti-neoplasic properties of thalidomide and to reduce its toxicity. The molecular mechanism of action of lenalidomide is unclear, but its therapeutic activity is mainly due to its well defined anti-inflammatory, immunomodulatory, anti-proliferative and anti-angiogenic properties. In relapsed or refractory multiple myeloma (MM), lenalidomide, combined with standard dose dexamethasone, is superior to dexamethasone alone in terms of time to progression, response rate and over…

Involvement of hepcidin in the anemia of multiple myeloma.

PURPOSE: Hepcidin is a liver-produced peptide implicated in the anemia of inflammation. Because interleukin (IL)-6 is a potent inducer of hepcidin expression and its levels are elevated in multiple myeloma, we studied the role of hepcidin in the anemia of multiple myeloma. EXPERIMENTAL DESIGN: Urinary hepcidin and serum levels of IL-6, ferritin, C-reactive protein, tumor necrosis factor-alpha, and IL-1 beta were studied in newly diagnosed myeloma patients. In vitro hepcidin induction assay was assessed by real-time PCR assay. RESULTS: Pretreatment urinary hepcidin levels in 44 patients with …

The pathogenesis of the bone disease of multiple myeloma.

Multiple myeloma is a fatal hematologic malignancy associated with clonal expansion of malignant plasma cells within the bone marrow and the development of a destructive osteolytic bone disease. The principal cellular mechanisms involved in the development of myeloma bone disease are an increase in osteoclastic bone resorption, and a reduction in bone formation. Myeloma cells are found in close association with sites of active bone resorption, and the interactions between myeloma cells and other cells within the specialized bone marrow microenvironment are essential, both for tumor growth and …

Lenalidomide in myelodysplastic syndrome and multiple myeloma.

The use of thalidomide is limited by adverse effects of sedation, constipation, neuropathy and thromboembolism. In order to discover more po … h dexamethasone, has been compared with dexamethasone alone in patients with relapsed or refractory multiple myeloma (MM) in two studies (MM-009 in North America and MM-010 in Europe, Israel and Australia). In these two phase III trials, lenalidomide demonstrated impressive (58-59%) response rates with dexamethasone. Lenalidomide has also been shown to overcome th …