Emerging Trends in the Clinical Use of Bortezomib in Multiple Myeloma

2005 ◽  
Vol 6 (2) ◽  
pp. 84-88 ◽  
Author(s):  
Paul G. Richardson ◽  
Robert Schlossman ◽  
Constantine Mitsiades ◽  
Teru Hideshima ◽  
Nikhil Munshi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Use ◽  
Emerging Trends

Thalidomide-Associated Thrombocytopenia

2005 ◽  
Vol 39 (11) ◽  
pp. 1936-1939 ◽  
Author(s):  
Michiel Duyvendak ◽  
Mark Naunton ◽  
Bert J Kingma ◽  
Jacobus RBJ Brouwers
Keyword(s):  
Multiple Myeloma ◽  
Laboratory Testing ◽  
Hematologic Toxicity ◽  
Antineoplastic Drugs ◽  
Clinical Use ◽  
Adverse Consequence ◽  
Shortness Of Breath ◽  
Probability Scale ◽  
Case Summary ◽  
One Year

OBJECTIVE To report thrombocytopenia in a patient prescribed thalidomide for multiple myeloma (MM). CASE SUMMARY A 70-year-old woman was diagnosed in 2003 with MM. At diagnosis, melphalan 0.25 mg/kg/day and prednisolone 2 mg/kg/day were started; however, the patient became refractory to therapy. Melphalan and prednisolone were discontinued, and monotherapy with dexamethasone 40 mg for 12 days per month was started. The patient's hematologic condition deteriorated again after about one year; dexamethasone was discontinued, and treatment with oral thalidomide 200 mg/day was initiated. About 2 weeks after thalidomide administration, the woman developed disabling adverse effects (flu-like symptoms, swollen fingers, rash and hematoma on her legs, shortness of breath, dry mouth, multiple petechiae). Laboratory testing showed neutropenia (neutrophils 0.4 × 109/L) and thrombocytopenia (platelets 58 × 109/L). Thalidomide was promptly discontinued; within 3 weeks, the laboratory values returned to pretreatment levels (1.3 × 109/L and 267 × 109/L, respectively) and her symptoms disappeared. DISCUSSION Thrombocytopenia is a rarely reported hematologic adverse consequence of thalidomide therapy. A recent report identified 5 patients who developed thrombocytopenia while undergoing monotherapy with thalidomide for MM. According to the Naranjo probability scale, thalidomide was classified as the probable cause of thrombocytopenia in our patient. CONCLUSIONS Unlike other antineoplastic drugs, thalidomide is rarely reported to cause severe hematologic toxicity. We present this case to increase clinicians’ awareness for the potential of thalidomide to adversely affect platelet counts, particularly because its effectiveness in MM will likely result in expansion of its clinical use.

CP-031 Clinical use of lenalidomide for the treatment of multiple myeloma

2016 ◽  
Vol 23 (Suppl 1) ◽  
pp. A13.3-A14
Author(s):  
B Monje ◽  
V Escudero-Vilaplana ◽  
JL Revuelta ◽  
X Garcia-Gonzalez ◽  
C Ortega-Navarro ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Use

Validation of the Nextseq 500 and Development of a High-Throughput NGS Pipeline for Identifying Clinically-Relevant Gene Variants in Multiple Myeloma Specimens

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5346-5346
Author(s):  
Agnieszka K. Zielinska ◽  
Kenton Leigh ◽  
Horacio Gomez ◽  
Ryan K Van Laar
Keyword(s):  
Gene Expression ◽  
Multiple Myeloma ◽  
Bone Marrow ◽  
High Throughput ◽  
Bone Marrow Aspirate ◽  
Relative Effectiveness ◽  
Gene Expression Signature ◽  
Molecular Profiling ◽  
Clinical Use ◽  
Dna And Rna

Abstract As molecular profiling technologies have evolved, our understanding of multiple myeloma heterogeneity and the relative effectiveness of treatment options have increased dramatically. Most recently, next generation sequencing (NGS) studies have provided a new degree of molecular resolution into this disease, however it remains a challenge to translate these methodologies and insights from research tools to widely-available clinical assays which can be performed as part of routine patient care. MyPRS® is a clinically and scientifically validated high-throughput gene-expression (Affymetrix) based assay available in all 50 US states. The CLIA and CAP-accredited laboratory workflow is able to isolate sufficient RNA from small amounts of fresh bone marrow aspirate, up to 72 hours post collection[1]. In order to expand the content of the MyPRS assay to include DNA-sequencing based variant, copy number and mutation detection, we have validated highly-scalable methods for isolating RNA and DNA separately and in parallel from individual patient specimens of varying quality and quantity. Yet another challenge of translational NGS profiling is performing complex laboratory procedures, developed primarily for research use only, with the requisite reproducibility and accuracy required for submission to regulatory agencies and ultimately for clinical use. Coupled with the protocols we developed for isolation of both DNA and RNA from small amounts of patient bone marrow aspirate, we performed an investigation of the Illumina NextSeq 500 and "on-site" BaseSpace data processing server. With the multiplexing and parallel processing capability of this platform we estimate being able to sequence, align and variant-call up to 150 myeloma-relevant genes at 1000x coverage per run. Results from our MM cell-line-, normal human- and NIST reference-DNA whole-exome-profiling studies show extremely high levels of technical reproducibility and agreement with results generated from 3rd party laboratories. In addition, we describe associations between the (RNA-expression based) prognostic, molecular subtyping and virtual karyotyping currently included in the MyPRS assay, with results from DNA-based exome profiling, performed on matched specimens. We believe findings underscore the need for comprehensive DNA and RNA based molecular profiling in order to make the most informed patient management decisions. 1. van Laar R, Flinchum R, Brown N, Ramsey J, Riccitelli S, Heuck C, Barlogie B, Shaughnessy Jr J: Translating a gene expression signature for multiple myeloma prognosis into a robust high-throughput assay for clinical use. BMC Medical Genomics 2014, 7 (1):25. Disclosures Zielinska: Signal Genetics: Employment. Leigh:Signal Genetics: Employment. Gomez:Signal Genetics: Employment. Van Laar:Signal Genetics: Employment.

scholarly journals Current and emerging immunotherapeutic approaches to the treatment of multiple myeloma

2019 ◽  
Vol 10 ◽  
pp. 204062071985417
Author(s):  
Dawn Swan ◽  
Kevin Lynch ◽  
Mark Gurney ◽  
Michael O’Dwyer
Keyword(s):  
Multiple Myeloma ◽  
Immune System ◽  
Immune Evasion ◽  
Proteasome Inhibitors ◽  
Standard Of Care ◽  
Bispecific Antibodies ◽  
Clinical Use ◽  
Immunomodulatory Drugs ◽  
Care Regimes

Multiple myeloma (MM) has a worldwide incidence of 1–5/100,000/year. Outcomes have improved significantly in recent years following incorporation of immunomodulatory drugs and proteasome inhibitors into standard-of-care regimes. MM is profoundly immunosuppressive, enabling immune evasion, proliferation and disease progression. The role of the immune system in MM is becoming increasingly characterized and understood, and numerous therapies are under development or in routine clinical use targeting these elements of MM pathogenesis. In this review we discuss the immunosuppressive effects of MM, then the therapies targeting these defects. Specifically, we review the monoclonal and bispecific antibodies, alongside adoptive cellular therapies currently under investigation.

Recommendations on the clinical use of bendamustine in lymphoproliferative syndromes and multiple myeloma

2015 ◽  
Vol 96 (5) ◽  
pp. 532-540 ◽  
Author(s):  
Francisco Javier Peñalver ◽  
Julio Delgado ◽  
Javier Loscertales ◽  
Jose Luis Sastre ◽  
Asunción Peña ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Use ◽  
Lymphoproliferative Syndromes

Clinical Use of AMD3100 to Mobilize CD34+ Cells in Patients Affected by Non-Hodgkin's Lymphoma or Multiple Myeloma

2005 ◽  
Vol 23 (16) ◽  
pp. 3871-3872 ◽  
Author(s):  
Giovanni Grignani ◽  
Eliana Perissinotto ◽  
Giuliana Cavalloni ◽  
Fabrizio Carnevale Schianca ◽  
Massimo Aglietta
Keyword(s):  
Multiple Myeloma ◽  
Hodgkin’S Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Clinical Use ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Cd34 Cells

Thalidomide increases thrombin generation in multiple myeloma patients

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7602-7602 ◽  
Author(s):  
D. Candelaria ◽  
B. Armijo ◽  
R. Montgomery ◽  
F. Lee ◽  
S. Moll ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Venous Thrombosis ◽  
Software Package ◽  
Thrombin Generation ◽  
Sodium Citrate ◽  
Normal Values ◽  
Statistical Significance ◽  
Standard Technique ◽  
Clinical Use ◽  
Study Results

7602 Background: Numerous reports have demonstrated that the clinical use of thalidomide (THAL) carries a risk for deep venous thrombosis. Only limited investigations into the causative mechanisms for this complication have been conducted. Thrombin generation is a global measurement of hyper or hypocoagulability that has not been used to examine the hypercoagulable state caused by THAL. The aim of this study was to determine if THAL affects thrombin generation in patients with multiple myeloma (MM). Methods: MM patients on and off THAL were recruited. Patients were considered to be “on THAL” if they had been taking the medication for at least three months and “off THAL” if they had not been taking the medication for at least three months. Coagulation tubes of blood containing 3.2% sodium citrate were drawn from each patient. Platelet poor plasma was prepared from these specimens using standard technique. The samples were snap frozen at -70 C and stored until analysis. Thrombin generation was measured using the Calibrated Automated Thrombogram as described by Hemker(Pathophysiol Haemo Thromb 2003;33:4–15) using a microplate fluorometer, the Fluoroskan Ascent from Thermo Electron and the Thrombinoscope software package. The endogenous thrombin potential or ETP (area under the thrombin generation curve) and peak thrombin generation (the maximum release of thrombin per unit of time) were the variables of interest for this study. Results: Twenty seven patients were recruited. Five were excluded from analysis because they were on warfarin or enoxaparin. The normal ETP in females is 1803 ± 241 nM*min and in males is 1745 ± 259 nM *min. Normal peak thrombin generation in females is 318.5 ± 52.9 nM and in males is 293.4 ± 48.5 nM. The t-test was used to compare subjects to normal values.Peak thrombin generation was significantly increased in the 9 subjects taking THAL, 374 ± 10.6 nM (p<0.001) and in the 13 subjects not taking THAL, 352 ± 14.7 nM (p=0.009) when compared to normal values. The ETP was not significantly increased 1818 ± 10.7 nM*min (p=0.69) in subjects not taking THAL. However, ETP was increased in subjects taking THAL, 1939± 90 nM*min and showed a trend toward statistical significance (p=0.10). Conclusions: Thalidomide therapy increases thrombin generation significantly in patients with MM. [Table: see text]

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