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t(4:14) multiple myeloma

Jesús F San-Miguel, Vania T M Hungria, Sung-Soo Yoon, Meral Beksac, Meletios A Dimopoulos, Ashraf Elghandour, Wieslaw W Jedrzejczak, Andreas Günther, Thanyaphong N Nakorn, Noppadol Siritanaratkul, Robert L Schlossman, Jian Hou, Philippe Moreau, Sagar Lonial, Jae H Lee, Hermann Einsele, Monika Sopala, Bourras-Rezki Bengoudifa, Florence Binlich, Paul G Richardson
BACKGROUND: Panobinostat plus bortezomib and dexamethasone significantly increased median progression-free survival compared with placebo plus bortezomib and dexamethasone in the phase 3 PANORAMA 1 trial. Here, we present the final overall survival analysis for this trial. METHODS: PANORAMA 1 is a randomised, placebo-controlled, double-blind, phase 3 trial of patients with relapsed or relapsed and refractory multiple myeloma with one to three previous treatments...
October 14, 2016: Lancet Haematology
Thomas Greuter, Martin Browne, Corina Dommann-Scherrer, Daniel Binder, Christoph Renner, Ursula Kapp
In the present study, the case of a 41-year-old man with immunoglobulin (Ig)M multiple myeloma (MM) that presented with an unusually non-aggressive clinical course who has survived for >9 years to date, is presented. Initial diagnosis of symptomatic MM was established according to the International Myeloma Working Group consensus statement and guidelines. Due to the mild symptoms, no therapy was administered and the patient was closely followed up. Eight years after initial diagnosis, clinical, morphological and genetic progression occurred with the development of hypercalcemia, progressively deteriorating polyneuropathy, clonal expansion of plasma cells up to 50% of hematopoietic cells and demonstration of the typical t(11;14) translocation (Ig heavy chain locus rearrangement)...
October 2016: Oncology Letters
Salomon Manier, Karma Salem, Siobhan V Glavey, Aldo M Roccaro, Irene M Ghobrial
Multiple myeloma (MM) is a genetically complex disease. The past few years have seen an evolution in cancer research with the emergence of next-generation sequencing (NGS), enabling high throughput sequencing of tumors-including whole exome, whole genome, RNA, and single-cell sequencing as well as genome-wide association study (GWAS). A few inherited variants have been described, counting for some cases of familial disease. Hierarchically, primary events in MM can be divided into hyperdiploid (HDR) and nonhyperdiploid subtypes...
2016: Cancer Treatment and Research
Christian Straka, Peter Liebisch, Hans Salwender, Burkhard Hennemann, Bernd Metzner, Stefan Knop, Sigrid Adler-Reichel, Christian Gerecke, Hannes Wandt, Martin Bentz, Tim Hendrik Bruemmendorf, Marcus Hentrich, Michael Pfreundschuh, Hans-Heinrich Wolf, Orhan Sezer, Ralf Bargou, Wolfram Jung, Lorenz Trümper, Bernd Hertenstein, Else Heidemann, Helga Bernhard, Nicola Lang, Norbert Frickhofen, Holger Hebart, Ralf Schmidmaier, Andreas Sandermann, Tobias Dechow, Albrecht Reichle, Brigitte Schnabel, Kerstin Schäfer-Eckart, Christian Langer, Martin Gramatzki, Axel Hinke, Bertold Emmerich, Hermann Einsele
Autologous transplantation is controversial for older patients with multiple myeloma. The role of age-adjusted high-dose melphalan and the impact of preceeding induction chemotherapy cycles has been unclear. A total of 434 patients 60 to 70 years of age were randomly assigned to 4 cycles of standard anthracycline-based induction chemotherapy or no induction cycles. For all patients, double autologous transplantation after melphalan 140 mg/m2 (MEL140) was planned. The primary end point was progression-free survival...
August 4, 2016: Haematologica
Inger S Nijhof, Laurens E Franssen, Mark-David Levin, Gerard M J Bos, Annemiek Broijl, Saskia K Klein, Harry R Koene, Andries C Bloem, Aart Beeker, Laura M Faber, Ellen van der Spek, Paula F Ypma, Reinier Raymakers, Dick-Johan van Spronsen, Peter E Westerweel, Rimke Oostvogels, Jeroen van Velzen, Berris van Kessel, Tuna Mutis, Pieter Sonneveld, Sonja Zweegman, Henk M Lokhorst, Niels W C J van de Donk
The prognosis of multiple myeloma (MM) patients who become refractory to lenalidomide and bortezomib is very poor, indicating the need for new therapeutic strategies for these patients. Next to the development of new drugs, the strategy of combining agents with synergistic activity may also result in clinical benefit for patients with advanced myeloma. We have previously shown in a retrospective analysis that lenalidomide combined with continuous low-dose cyclophosphamide and prednisone (REP) had remarkable activity in heavily pretreated, lenalidomide-refractory MM patients...
September 19, 2016: Blood
Sheela V Godbole, Karabi Nandy, Mansi Gauniyal, Pallavi Nalawade, Suvarna Sane, Shravani Koyande, Joy Toyama, Asha Hegde, Phil Virgo, Kishor Bhatia, Ramesh S Paranjape, Arun R Risbud, Sam M Mbulaiteye, Ronald T Mitsuyasu
We utilized computerized record-linkage methods to link HIV and cancer databases with limited unique identifiers in Pune, India, to determine feasibility of linkage and obtain preliminary estimates of cancer risk in persons living with HIV (PLHIV) as compared with the general population.Records of 32,575 PLHIV were linked to 31,754 Pune Cancer Registry records (1996-2008) using a probabilistic-matching algorithm. Cancer risk was estimated by calculating standardized incidence ratios (SIRs) in the early (4-27 months after HIV registration), late (28-60 months), and overall (4-60 months) incidence periods...
September 2016: Medicine (Baltimore)
Alessandra Larocca, Antonio Palumbo
The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice...
September 6, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Leo Rasche, Christoph Röllig, Gernot Stuhler, Sophia Danhof, Stephan Mielke, Goetz Ulrich Grigoleit, Lea Dissen, Lea Schemmel, Jan Moritz Middeke, Viktoria Rücker, Martin Schreder, Johannes Schetelig, Martin Bornhäuser, Hermann Einsele, Christian Thiede, Stefan Knop
Although generally not applied as first-line treatment of multiple myeloma, allogeneic hematopoietic cell transplantation (allo-SCT) can still be chosen as ultimate escalation approach in high-risk patients, preferentially within the framework of clinical trials. In this study, we investigated whether decreasing donor chimerism (DC) is predictive for relapse. In addition, we comprehensively determined the impact of several other disease- and treatment-related factors on outcome. One hundred fifty-five multiple myeloma patients whose DC status was followed serially by the short tandem repeat-based techniques at a single lab were included in this retrospective study...
November 2016: Biology of Blood and Marrow Transplantation
Michael Schmitt, Angela G Hückelhoven, Michael Hundemer, Anita Schmitt, Susanne Lipp, Martina Emde, Hans Salwender, Mathias Hänel, Katja Weisel, Uta Bertsch, Jan Dürig, Anthony D Ho, Igor Wolfgang Blau, Hartmut Goldschmidt, Anja Seckinger, Dirk Hose
BACKGROUND: Raising T-cell response against antigens either expressed on normal and malignant plasma cells (e.g. HM1.24) or aberrantly on myeloma cells only (e.g. cancer testis antigens, CTA) by vaccination is a potential treatment approach for multiple myeloma. RESULTS: Expression by GEP is found for HM1.24 in all, HMMR in 318/458 (69.4%), MAGE-A3 in 209/458 (45.6%), NY-ESO-1/2 in 40/458 (8.7%), and WT-1 in 4/458 (0.8%) of samples with the pattern being confirmed by RNA-sequencing...
August 11, 2016: Oncotarget
Emma C Scott, Parameswaran Hari, Manish Sharma, Jennifer Le-Rademacher, Jiaxing Huang, Dan Vogl, Muneer Abidi, Amer Beitinjaneh, Henry Fung, Siddhartha Ganguly, Gerhard Hildebrandt, Leona Holmberg, Matt Kalaycio, Shaji Kumar, Robert Kyle, Hillard Lazarus, Cindy Lee, Richard T Maziarz, Kenneth Meehan, Joseph Mikhael, Taiga Nishihori, Muthalagu Ramanathan, Saad Usmani, Jason Tay, David Vesole, Baldeep Wirk, Jean Yared, Bipin N Savani, Cristina Gasparetto, Amrita Krishnan, Tomer Mark, Yago Nieto, Anita D'Souza
Conventional cytogenetics and interphase fluorescence in situ hybridization (FISH) identify high-risk multiple myeloma (HRM) populations characterized by poor outcomes. We analyzed these differences among HRM versus non-HRM populations after upfront autologous hematopoietic cell transplantation (autoHCT). Between 2008 and 2012, 715 patients with multiple myeloma identified by FISH and/or cytogenetic data with upfront autoHCT were identified in the Center for International Blood and Marrow Transplant Research database...
October 2016: Biology of Blood and Marrow Transplantation
P Moreau, D Joshua, W-J Chng, A Palumbo, H Goldschmidt, R Hájek, T Facon, H Ludwig, L Pour, R Niesvizky, A Oriol, L Rosiñol, A Suvorov, G Gaidano, T Pika, K Weisel, V Goranova-Marinova, H H Gillenwater, N Mohamed, S Aggarwal, S Feng, M A Dimopoulos
The randomized phase 3 ENDEAVOR study (N=929) compared carfilzomib and dexamethasone (Kd) with bortezomib and dexamethasone (Vd) in relapsed multiple myeloma (RMM). We performed a subgroup analysis from ENDEAVOR in patients categorized by number of prior lines of therapy or by prior treatment. Median progression-free survival (PFS) for patients with one prior line was 22.2 months for Kd vs 10.1 months for Vd, and median PFS for patients with ⩾2 prior lines was 14.9 months for Kd vs 8.4 months for Vd. For patients with prior bortezomib exposure, the median PFS was 15...
August 5, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Victor H Jimenez-Zepeda, Peter Duggan, Paola Neri, Fariborz Rashid-Kolvear, Jason Tay, Nizar J Bahlis
BACKGROUND: A variety of validated prognostic markers for multiple myeloma has been described to help inform clinical practice. Recently, a robust system has been introduced for clinical use and is being adopted by the International Myeloma Working Group Revised International Staging System (RISS). The RISS was developed using data from patients enrolled in clinical trials. Consequently, its utility is less clear in unselected patients with myeloma. MATERIALS AND METHODS: All consecutive patients newly diagnosed with multiple myeloma treated and followed up at Tom Baker Cancer Center from January 2004 to October 2015 were included in the present study...
June 8, 2016: Clinical Lymphoma, Myeloma & Leukemia
R Hájek, T Masszi, M T Petrucci, A Palumbo, L Rosiñol, A Nagler, K L Yong, A Oriol, J Minarik, L Pour, M A Dimopoulos, V Maisnar, D Rossi, H Kasparu, J Van Droogenbroeck, D B Yehuda, I Hardan, M Jenner, M Calbecka, M Dávid, J de la Rubia, J Drach, Z Gasztonyi, S Górnik, X Leleu, M Munder, M Offidani, N Zojer, K Rajangam, Y-L Chang, J F San-Miguel, H Ludwig
This randomized, phase III, open-label, multicenter study compared carfilzomib monotherapy against low-dose corticosteroids and optional cyclophosphamide in relapsed and refractory multiple myeloma (RRMM). Relapsed and refractory multiple myeloma patients were randomized (1:1) to receive carfilzomib (10-min intravenous infusion; 20 mg/m(2) on days 1 and 2 of cycle 1; 27 mg/m(2) thereafter) or a control regimen of low-dose corticosteroids (84 mg of dexamethasone or equivalent corticosteroid) with optional cyclophosphamide (1400 mg) for 28-day cycles...
July 15, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
S Vincent Rajkumar
Multiple myeloma accounts for approximately 10% of hematologic malignancies.The diagnosis requires ≥10% clonal bone marrow plasma cells or a biopsy proven plasmacytoma plus evidence of one or more multiple myeloma defining events (MDE): CRAB (hypercalcemia, renal failure, anemia, or lytic bone lesions) features felt related to the plasma cell disorder, bone marrow clonal plasmacytosis ≥60%, serum involved/uninvolved free light chain (FLC) ratio ≥100 (provided involved FLC is ≥100 mg/L), or >1 focal lesion on magnetic resonance imaging...
July 2016: American Journal of Hematology
Tilmann Bochtler, Ute Hegenbart, Christina Kunz, Axel Benner, Christoph Kimmich, Anja Seckinger, Dirk Hose, Hartmut Goldschmidt, Martin Granzow, Peter Dreger, Anthony D Ho, Anna Jauch, Stefan O Schönland
Cytogenetic aberrations detected by interphase fluorescence in situ hybridization (iFISH) of plasma cells are routinely evaluated as prognostic markers in multiple myeloma. This long-term follow-up study aimed to assess the prognosis of systemic light chain amyloidosis (AL) patients treated with high-dose melphalan (HDM) chemotherapy and autologous stem cell transplantation, depending on iFISH results. Therefore, we analyzed a consecutive cohort of 123 AL patients recruited from 2003 to 2014. HDM was safe, with only 1 of 123 patients dying as a result of treatment-related mortality, and effective, with a complete remission (CR) rate of 34%...
July 28, 2016: Blood
Renata Kiyomi Kishimoto, Sarah Lee Vaughan Vulcani de Freitas, Cristina Alonso Ratis, Daniela Borri, Roberta Sitnik, Elvira Deolinda Rodrigues Pereira Velloso
BACKGROUND: Multiple myeloma is a plasma cell neoplasm with acquired genetic abnormalities of clinical and prognostic importance. Multiple myeloma differs from other hematologic malignancies due to a high fraction of low proliferating malignant plasma cells and the paucity of plasma cells in bone marrow aspiration samples, making cytogenetic analysis a challenge. An abnormal karyotype is found in only one-third of patients with multiple myeloma and interphase fluorescence in situ hybridization is the most useful test for studying the chromosomal abnormalities present in almost 90% of cases...
April 2016: Revista Brasileira de Hematologia e Hemoterapia
Yuan Jian, Xiaolei Chen, Huixing Zhou, Wanqiu Zhu, Nian Liu, Chuanying Geng, Wenming Chen
The identification of specific cytogenetic abnormalities by interphase fluorescence in situ hybridization (i-FISH) has become a routine procedure for prognostic stratification of multiple myeloma (MM) patients. In this study, the prognostic significance of cytogenetic abnormalities detected by interphase fluorescence in situ hybridization (iFISH) in 229 newly diagnosed multiple myeloma patients was retrospectively analyzed. Results showed that del (17p), t(4;14), and 1q21 gain were adverse predictors of progression-free survival (PFS)...
May 2016: Medicine (Baltimore)
Binod Dhakal, Anita D'Souza, Michael Martens, Jonathan Kapke, Alexandra M Harrington, Marcelo Pasquini, Wael Saber, William R Drobyski, Mei Jie Zhang, Mehdi Hamadani, Parameswaran N Hari
BACKGROUND: Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative option for multiple myeloma (MM). We analyzed our experience of allo-HCT in MM and examined outcomes in 77 consecutive patients with MM receiving allo-HCT from matched sibling (n = 69) or unrelated donors (n = 8). The primary objectives were to assess overall survival (OS), progression-free survival (PFS), and non-relapse mortality in these patients. PATIENTS AND METHODS: Sixty-six patients received non-myeloablative/reduced-intensity conditioning regimens, while 11 received myeloablative regimens...
July 2016: Clinical Lymphoma, Myeloma & Leukemia
Merav Leiba, Adrian Duek, Ninette Amariglio, Abraham Avigdor, Noam Benyamini, Izhar Hardan, Itay Zilbershats, Chezi Ganzel, Olga Shevetz, Ilya Novikov, Yossi Cohen, Galina Ishoev, Gabriela Rozic, Arnon Nagler, Luba Trakhtenbrot
The most common translocation in multiple myeloma (MM) is t(11;14)(q13;q32). According to several studies, this translocation represents a unique subset of patients with relatively favorable outcomes. Using combined analyses of morphology and fluorescence in situ hybridization (I-FISH), we examined the co-occurrence rates of t(11;14) with seven chromosomal aberrations (CAs), del(13q), del(17p), del(1p), gain(1q), multiple gains(1q), del(16q), and del(IGH), and assessed the effect of the different combinations on patient outcomes, with overall survival (OS) as the main outcome measure...
September 2016: Genes, Chromosomes & Cancer
Philippe Moreau, Tamás Masszi, Norbert Grzasko, Nizar J Bahlis, Markus Hansson, Ludek Pour, Irwindeep Sandhu, Peter Ganly, Bartrum W Baker, Sharon R Jackson, Anne-Marie Stoppa, David R Simpson, Peter Gimsing, Antonio Palumbo, Laurent Garderet, Michele Cavo, Shaji Kumar, Cyrille Touzeau, Francis K Buadi, Jacob P Laubach, Deborah T Berg, Jianchang Lin, Alessandra Di Bacco, Ai-Min Hui, Helgi van de Velde, Paul G Richardson
BACKGROUND: Ixazomib is an oral proteasome inhibitor that is currently being studied for the treatment of multiple myeloma. METHODS: In this double-blind, placebo-controlled, phase 3 trial, we randomly assigned 722 patients who had relapsed, refractory, or relapsed and refractory multiple myeloma to receive ixazomib plus lenalidomide-dexamethasone (ixazomib group) or placebo plus lenalidomide-dexamethasone (placebo group). The primary end point was progression-free survival...
April 28, 2016: New England Journal of Medicine
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