Multiple Myeloma

Kc, Anderson; Alsina, María; Bensinger, William I.; Js, Biermann; Asher, Chanan-Khan; Cohen, Adam D.; Devine, Steven M.; Djulbegovic, B.; Gasparetto, Cristina; Ca, Huff; Jagasia, Madan; Medeiros, Bruno C.; Meredith, Ruby F.; Raje, Noopur; Schriber, Jeffrey; Singhal, Surbhi; Somlo, George; Stockerl-Goldstein, Keith; Tricot, G.; Vose, J. M.; Weber, Dirk; Yahalom, Joachim; Yunus, Furhan

doi:10.6004/jnccn.2009.0061

Cited by 101 publications

(18 citation statements)

References 86 publications

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“…The duration of the first remission and the timing of the relapse are key determinants for the treatment strategy at the relapse. The National Comprehensive Cancer Network clinical practice guidelines state that patients with MM who are not refractory to the initial therapy (relapse >6 months after completion of the previous therapy) may be retreated with the same regimen (15). Bortezomib is a weak substrate for multi-drug resistance efflux pumps and has the potential to avoid resistance.…”

Section: Discussionmentioning

confidence: 99%

Short-course bortezomib-based retreatment for patients with multiple myeloma who had received bortezomib-thalidomide-dexamethasone (VTD) as an initial therapy: A single-center case series

Mao

Cheng

Chen

et al. 2014

Experimental and Therapeutic Medicine

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Studies have shown that the bortezomib-based retreatment of patients with multiple myeloma (MM) may prolong control of the disease. The optimal duration of bortezomib-based retreatment in relapsed or refractory MM is unknown. The present retrospective study evaluated the efficacy and safety of short-course bortezomib-based retreatment in patients who had received bortezomib-thalidomide-dexamethasone (VTD) treatment for the initial therapy of newly diagnosed MM. The clinical records of 20 patients who had received short-course bortezomib-based retreatment in a single center were reviewed. Patients received a median of two cycles of bortezomib as the retreatment and the overall response rate was 90%. Six (30%), eight (40%) and four (20%) patients achieved a complete response (CR), a very good partial response and a partial response, respectively. Of the 10 patients who had achieved a CR during the initial VTD treatment, six experienced a repeat CR during the retreatment. The median duration of the response was nine months and the median time to progression was 10.5 months. The most common grade I and II adverse events were thrombocytopenia and neutropenia. The short-course bortezomib-based retreatment was well tolerated and the favorable response rates observed suggest that it may be an effective and convenient treatment option for certain patients, particularly elderly patients.

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Section: Discussionmentioning

confidence: 99%

Short-course bortezomib-based retreatment for patients with multiple myeloma who had received bortezomib-thalidomide-dexamethasone (VTD) as an initial therapy: A single-center case series

Mao

Cheng

Chen

et al. 2014

Experimental and Therapeutic Medicine

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“…The general treatment strategy in this study adhered to the suggestions for multiple myeloma in international treatment guidelines 13. Briefly, for patients who were transplant eligible, induction chemotherapy consisting of vincristine, doxorubicin, and dexamethasone (VAD) and thalidomide-based regimens were the most commonly used front-line therapies.…”

Section: Methodsmentioning

confidence: 99%

Chronic hepatitis virus infection in patients with multiple myeloma: clinical characteristics and outcomes

Teng

Liu

et al. 2011

Clinics

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OBJECTIVES:Cytotoxic agents and steroids are used to treat lymphoid malignancies, but these compounds may exacerbate chronic viral hepatitis. For patients with multiple myeloma, the impact of preexisting hepatitis virus infection is unclear. The aim of this study is to explore the characteristics and outcomes of myeloma patients with chronic hepatitis virus infection.METHODS:From 2003 to 2008, 155 myeloma patients were examined to determine their chronic hepatitis virus infection statuses using serologic tests for the hepatitis B (HBV) and C viruses (HCV). Clinical parameters and outcome variables were retrieved via a medical chart review.RESULTS:The estimated prevalences of chronic HBV and HCV infections were 11.0% (n = 17) and 9.0% (n = 14), respectively. The characteristics of patients who were hepatitis virus carriers and those who were not were similar. However, carrier patients had a higher prevalence of conventional cytogenetic abnormalities (64.3% vs. 25.0%). The cumulative incidences of grade 3-4 elevation of the level of alanine transaminase, 30.0% vs. 12.0%, and hyperbilirubinemia, 20.0% vs. 1.6%, were higher in carriers as well. In a Kaplan-Meier analysis, carrier patients had worse overall survival (median: 16.0 vs. 42.4 months). The prognostic value of carrier status was not statistically significant in the multivariate analysis, but an age of more than 65 years old, the presence of cytogenetic abnormalities, a beta-2-microglobulin level of more than 3.5 mg/L, and a serum creatinine level of more than 2 mg/dL were independent factors associated with poor prognosis.CONCLUSION:Myeloma patients with chronic hepatitis virus infections might be a distinct subgroup, and close monitoring of hepatic adverse events should be mandatory.

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“…The development of high-dose melphalan with autologous stem cell transplant for younger (<65 years) fitter patients 10, 11, 12 and new therapies incorporating combinations of corticosteroids and conventional chemotherapy agents with immunomodulatory drugs (thalidomide and lenalidomide), and proteasome inhibitors (bortezomib) have increased median survival to 4–5 years. 13, 14, 15 However, high-dose chemotherapy and autologous stem cell transplant are not suitable for elderly frail patients due to significant toxicities. Approximately 85% of myeloma patients are >60 years of age with a median age at presentation of ∼70 years and median survival has remained 2–3 years in the over 70 cohort.…”

Section: Introductionmentioning

confidence: 99%

Redeployment-based drug screening identifies the anti-helminthic niclosamide as anti-myeloma therapy that also reduces free light chain production

Khanim

Merrick

Giles

et al. 2011

Blood Cancer Journal

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Despite recent therapeutic advancements, multiple myeloma (MM) remains incurable and new therapies are needed, especially for the treatment of elderly and relapsed/refractory patients. We have screened a panel of 100 off-patent licensed oral drugs for anti-myeloma activity and identified niclosamide, an anti-helminthic. Niclosamide, at clinically achievable non-toxic concentrations, killed MM cell lines and primary MM cells as efficiently as or better than standard chemotherapy and existing anti-myeloma drugs individually or in combinations, with little impact on normal donor cells. Cell death was associated with markers of both apoptosis and autophagy. Importantly, niclosamide rapidly reduced free light chain (FLC) production by MM cell lines and primary MM. FLCs are a major cause of renal impairment in MM patients and light chain amyloid and FLC reduction is associated with reversal of tissue damage. Our data indicate that niclosamides anti-MM activity was mediated through the mitochondria with rapid loss of mitochondrial membrane potential, uncoupling of oxidative phosphorylation and production of mitochondrial superoxide. Niclosamide also modulated the nuclear factor-κB and STAT3 pathways in MM cells. In conclusion, our data indicate that MM cells can be selectively targeted using niclosamide while also reducing FLC secretion. Importantly, niclosamide is widely used at these concentrations with minimal toxicity.

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Multiple Myeloma

Cited by 101 publications

References 86 publications

Short-course bortezomib-based retreatment for patients with multiple myeloma who had received bortezomib-thalidomide-dexamethasone (VTD) as an initial therapy: A single-center case series

Short-course bortezomib-based retreatment for patients with multiple myeloma who had received bortezomib-thalidomide-dexamethasone (VTD) as an initial therapy: A single-center case series

Chronic hepatitis virus infection in patients with multiple myeloma: clinical characteristics and outcomes

Redeployment-based drug screening identifies the anti-helminthic niclosamide as anti-myeloma therapy that also reduces free light chain production

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