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relapsed multiple myeloma

Elizabeth Bilotti, David H Vesole, Laura McBride, Linda Schmidt, Zhijie Gao, Madiha Gilani, Ann McNeill, Urszula Bednarz, Joshua Richter, Anthony Mato, Thorsten Graef, David S Siegel
BACKGROUND: This is a retrospective chart review to evaluate the efficacy of the addition of vorinostat to lenalidomide and dexamethasone in patients with multiple myeloma relapsed/refractory to lenalidomide and dexamethasone. METHODS: Charts from 26 consecutive patients able to obtain commercial vorinostat were analyzed for response and safety data. RESULTS: The overall response rate was 31%, and the clinical beneficial rate was 50%. The median duration of response was 3 months, and the median overall survival was 28...
October 2016: Clinical Lymphoma, Myeloma & Leukemia
Silvia Mangiacavalli, A Pompa, V Ferretti, C Klersy, F Cocito, M Varettoni, C S Cartia, M Cazzola, A Corso
Extramedullary relapse (EMR) represents a poor prognostic marker in the course of multiple myeloma (MM). We reviewed data from 329 patients, diagnosed between 2000 and 2010, without extramedullary disease at onset to explore possible risk factors for EMR. The median overall survival of our study cohort was 6.4 years. The risk of EMR was 28 % with a median time from diagnosis to first EMR of 2.2 years (0.2-9.1 years). Patients with soft tissue masses located in extra-osseous organs (EMR-S) showed the worst outcome, compared to those with tumor masses arising from adjacent bone (EMR-B) (median OS 1...
October 21, 2016: Annals of Hematology
Muhammad Husnain, Sandra Kurtin, Nikki Barkett, Irbaz Bin Riaz, Amit Agarwal
Patients with relapsed and refractory multiple myeloma have poor prognosis. A recent analysis of patients with relapsed and refractory multiple myeloma who were refractory to both proteasome inhibitors and immunomodulatory drugs showed the median overall survival of 9 months only. Daratumumab is the first-in-class human monoclonal antibody against CD38 cells which was studied in phase I/II trials for treatment of these patients with relapsed refractory multiple myeloma. It showed an overall response rate of 36% and a median overall survival (OS) of 17 months in these patients...
2016: Case Reports in Oncological Medicine
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
Xiaoning Wang, Pengcheng He, Caili Guo, Chunhong Sun, Mei Zhang
INTRODUCTION: To investigate the safety and efficacy of the combination regimen vincristine, cyclophosphamide, melphalan or mitoxantrone and prednisone (VCMP) plus thalidomide as first-line induction therapy for newly diagnosed multiple myeloma (MM). METHODS: Three hundred and ninety-six symptomatic, newly diagnosed MM patients were treated with VCMP plus thalidomide in our hospital for the past 11 years, and clinical data of these patients were retrospectively analyzed...
October 14, 2016: Asia-Pacific Journal of Clinical Oncology
Soushi Ibata, Tsutomu Sato, Hiroyuki Kuroda, Yasuhiro Nagamachi, Satoshi Iyama, Akihito Fujimi, Yusuke Kamihara, Yuichi Konuma, Masahiro Yoshida, Ayumi Tatekoshi, Akari Hashimoto, Hiroto Horiguchi, Kaoru Ono, Kazuyuki Murase, Kohichi Takada, Koji Miyanishi, Masayoshi Kobune, Yasuo Hirayama, Junji Kato
PURPOSE: Consolidation/maintenance therapy induces deep remission in patients with multiple myeloma (MM); however, the most suitable regimen has been under investigation. The combination therapy with bortezomib, lenalidomide and dexamethasone (VRD) is a powerful regimen for relapsed/refractory as well as newly diagnosed MM as an induction therapy. However, severe adverse events (AEs) may become a problem when VRD is introduced without dose reduction as a consolidation/maintenance therapy...
October 13, 2016: Cancer Chemotherapy and Pharmacology
Prahlad V Raninga, Giovanna Di Trapani, Slavica Vuckovic, Kathryn F Tonissen
Multiple myeloma (MM) is an incurable plasma B cell malignancy. Despite recent advancements in anti-MM therapies, development of drug resistance remains a major clinical hurdle. DJ-1, a Parkinson's disease-associated protein, is upregulated in many cancers and its knockdown suppresses tumor growth and overcomes chemoresistance. However, the role of DJ-1 in MM remains unknown. Using gene expression databases we found increased DJ-1 expression in MM patient cells, which correlated with shorter overall survival and poor prognosis in MM patients...
October 12, 2016: Apoptosis: An International Journal on Programmed Cell Death
Seok Jin Kim, Soo-Mee Bang, Yoon Seok Choi, Deog-Yeon Jo, Jin Seok Kim, Hyewon Lee, Hyeon Seok Eom, Dok Hyun Yoon, Cheolwon Suh, Je-Jung Lee, Junshik Hong, Jae Hoon Lee, Youngil Koh, Kihyun Kim, Sung-Soo Yoon, Chang-Ki Min
BACKGROUND: Bendamustine may be a potential treatment option for patients with myeloma, but little is known about the utility of bendamustine as a salvage treatment, especially in Asian patients. METHODS: We performed a multicenter retrospective study of patients with relapsed or refractory myeloma who received bendamustine and prednisone. RESULTS: The records of 65 heavily pre-treated patients, who had undergone bortezomib and lenalidomide treatment (median number of previous treatments: 5), were analyzed...
September 2016: Blood Research
E Terpos, D Christoulas, E Kastritis, T Bagratuni, M Gavriatopoulou, M Roussou, A Papatheodorou, E Eleutherakis-Papaiakovou, N Kanellias, C Liakou, I Panagiotidis, M Migkou, P Kokkoris, L A Moulopoulos, M A Dimopoulos
Periostin is an extracellular matrix protein that is implicated in the biology of normal bone remodeling and in different cancer cell growth and metastasis. However, there is no information on the role of periostin in multiple myeloma (MM). Thus, we evaluated periostin in six myeloma cell lines in vitro; in the bone marrow plasma and serum of 105 newly diagnosed symptomatic MM (NDMM) patients and in the serum of 23 monoclonal gammopathy of undetermined significance (MGUS), 33 smoldering MM (SMM) patients, 30 patients at the plateau phase post-first-line therapy, 30 patients at first relapse and 30 healthy controls...
October 7, 2016: Blood Cancer Journal
Meletios A Dimopoulos, Albert Oriol, Hareth Nahi, Jesus San-Miguel, Nizar J Bahlis, Saad Z Usmani, Neil Rabin, Robert Z Orlowski, Mieczyslaw Komarnicki, Kenshi Suzuki, Torben Plesner, Sung-Soo Yoon, Dina Ben Yehuda, Paul G Richardson, Hartmut Goldschmidt, Donna Reece, Steen Lisby, Nushmia Z Khokhar, Lisa O'Rourke, Christopher Chiu, Xiang Qin, Mary Guckert, Tahamtan Ahmadi, Philippe Moreau
Background Daratumumab showed promising efficacy alone and with lenalidomide and dexamethasone in a phase 1-2 study involving patients with relapsed or refractory multiple myeloma. Methods In this phase 3 trial, we randomly assigned 569 patients with multiple myeloma who had received one or more previous lines of therapy to receive lenalidomide and dexamethasone either alone (control group) or in combination with daratumumab (daratumumab group). The primary end point was progression-free survival. Results At a median follow-up of 13...
October 6, 2016: New England Journal of Medicine
Shaji K Kumar, Betsy R LaPlant, Craig B Reeder, Vivek Roy, Alese E Halvorson, Francis Buadi, Morie A Gertz, P Leif Bergsagel, Angela Dispenzieri, Melanie A Thompson, Jamie Crawley, Prashant Kapoor, Joseph Mikhael, Keith Stewart, Suzanne R Hayman, Yi L Hwa, Wilson Gonsalves, Thomas E Witzig, Sikander Ailawadhi, David Dingli, Ronald S Go, Yi Lin, Candido E Rivera, S Vincent Rajkumar, Martha Q Lacy
Proteasome inhibitors have become an integral part of myeloma therapy. Considerable efforts have gone into optimizing this therapeutic approach in order to obtain maximal proteasome inhibition with least toxicity. Ixazomib is the first oral proteasome inhibitor to enter the clinic and has been studied as a single agent as well as in various combinations. The current trial was designed to examine the efficacy and toxicity of combining two different doses of ixazomib (4 mg and 5.5mg given weekly for 3 of 4 weeks) with 40 mg weekly of dexamethasone, in relapsed myeloma...
October 4, 2016: Blood
Yoichi Imai, Eri Ohta, Shu Takeda, Satoko Sunamura, Mariko Ishibashi, Hideto Tamura, Yan-Hua Wang, Atsuko Deguchi, Junji Tanaka, Yoshiro Maru, Toshiko Motoji
Multiple myeloma (MM) is a relapsed and refractory disease, one that highlights the need for developing new molecular therapies for overcoming of drug resistance. Addition of panobinostat, a histone deacetylase (HDAC) inhibitor, to bortezomib and dexamethasone improved progression-free survival (PFS) in relapsed and refractory MM patients. Here, we demonstrate how calcineurin, when inhibited by immunosuppressive drugs like FK506, is involved in myeloma cell growth and targeted by panobinostat. mRNA expression of PPP3CA, a catalytic subunit of calcineurin, was high in advanced patients...
April 21, 2016: JCI Insight
Paola Neri, Nizar J Bahlis, Claudia Paba-Prada, Paul Richardson
Survival outcomes of patients with Multiple Myeloma (MM) have improved over the last decade due to the introduction of novel agents such as the immunomodulatory drugs thalidomide, lenalidomide (Len) and pomalidomide, and the proteasome inhibitors bortezomib (BTZ) and carfilzomib [1, 2]. However, despite these major advances, MM remains largely incurable and almost all patients relapse and require additional therapy [3]. The successful introduction of next generation novel agents including oral proteasome inhibitors, deacetylase inhibitors, and especially monoclonal antibodies as part of immunotherapy promises to further improve outcome...
2016: Cancer Treatment and Research
Hermann Einsele, Martin Schreder
Elotuzumab is a humanized monoclonal antibody targeting the extracellular domain of signaling lymphocytic activation molecule F7 (SLAMF7) highly expressed in multiple myeloma cells. Upon binding to myeloma cells, elotuzumab exerts its cytotoxic effects through antibody-dependent cellular cytotoxicity, the antibody-induced selective lysis of tumor cells by activated natural killer (NK) cells. Furthermore, elotuzumab has been shown to directly induce NK-cell activation by binding to SLAMF7 expressed on NK cells and to indirectly modulate T-cell function by promoting the secretion of cytokines from NK cells...
October 2016: Therapeutic Advances in Hematology
Jesus F San-Miguel, Hermann Einsele, Philippe Moreau
: Panobinostat is an oral pan-histone deacetylase inhibitor developed by Novartis. Panobinostat acts via epigenetic modification and inhibition of the aggresome pathway. In August 2015, the European Commission authorized panobinostat for use in combination with bortezomib and dexamethasone for the treatment of relapsed or relapsed and refractory multiple myeloma (MM) in patients who have received ≥2 prior regimens including bortezomib and an immunomodulatory drug. In January 2016, the National Institute for Health and Care Excellence recommended panobinostat for use in the same combination and patient population...
September 27, 2016: Advances in Therapy
Peter M Voorhees, Saad Z Usmani
The advent of the immunomodulatory drugs thalido-mide, lenalidomide, and pomalidomide; the proteasome inhib-itors bortezomib, carfilzomib, and ixazomib; the histone deacet-ylase inhibitor panobinostat; and the monoclonal antibodies elotuzumab and daratumumab has led to dramatic improvements in outcomes for patients with multiple myeloma. Along with progress in nontransplant therapy have come questions regarding the continued role of high-dose melphalan (HDM) supported by autologous stem cell transplant (ASCT) in the treatment of multiple myeloma...
September 2016: Clinical Advances in Hematology & Oncology: H&O
Lisa A Raedler
No abstract text is available yet for this article.
March 2016: American Health & Drug Benefits
Lisa A Raedler
No abstract text is available yet for this article.
March 2016: American Health & Drug Benefits
Lisa A Raedler
No abstract text is available yet for this article.
March 2016: American Health & Drug Benefits
Lisa A Raedler
No abstract text is available yet for this article.
March 2016: American Health & Drug Benefits
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