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https://www.readbyqxmd.com/read/28723635/meta-analysis-of-the-efficacy-of-treatments-for-newly-diagnosed-and-relapsed-refractory-multiple-myeloma-with-del-17p
#1
Jinghua Liu, Hui Yang, Xiaochan Liang, Yuxin Wang, Jian Hou, Yanqin Liu, Jigang Wang, Fan Zhou
We analyzed the treatment of newly diagnosed and relapsed/refractory multiple myeloma (NDMM/RRMM) patients with del(17p). Thirteen prospective studies that evaluated 3,187 MM patients, including 685with del(17p), were included in our meta-analysis. The incidence of del(17p) in NDMM and RRMM patients was similar (13% vs. 14%, respectively, P = 0.64, I2 = 94%). The overall response rate (ORR) to new agents was 40.5% and 67.1%, respectively, in RRMM patients with or without del(17p) (P = 0.1, I2 = 63.9%). NDMM patients with del(17p) treated with PAD (bortezomib, adriamycin, and dexamethasone) induction therapy followed by bortezomib maintenance therapy had higher progression-free survival (PFS) (25...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28700354/docking-of-cdk1-with-antibiotic-drugs-revealed-novel-therapeutic-value-in-breast-ductal-cancer-in-situ
#2
Zhong-Hai Ding, Jia Qi, An-Quan Shang, Yu-Jie Zhang, Jun Wei, Li-Qing Hu, Wei-Wei Wang, Man Yang
The aim of our research is to identify potential genes associated with Ductal carcinoma in situ (DCIS) through microarrays. The microarray dataset GS54665 were downloaded from the GEO(Gene Expression Omnibus) database. Dysregulated genes were screened and their associations with DCIS was analyzed by comprehensive bioinformatics tools. A total of 649 differential expression genes were identified between normal and DCIS samples, including 224 up-regulated genes and 425 down-regulated genes. Biological process annotation and pathway enrichment analysis identified several DCIS-related signaling pathways...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28684537/pomalidomide-bortezomib-and-dexamethasone-pvd-for-patients-with-relapsed-lenalidomide-refractory-multiple-myeloma
#3
Jonas Paludo, Joseph R Mikhael, Betsy R LaPlant, Alese E Halvorson, Shaji Kumar, Morie A Gertz, Suzanne R Hayman, Francis K Buadi, Angela Dispenzieri, John A Lust, Prashant Kapoor, Nelson Leung, Stephen J Russell, David Dingli, Ronald S Go, Yi Lin, Wilson I Gonsalves, Rafael Fonseca, P Leif Bergsagel, Vivek Roy, Taimur Sher, Asher A Chanan-Khan, Sikander Ailawadhi, A Keith Stewart, Craig B Reeder, Paul G Richardson, S Vincent Rajkumar, Martha Q Lacy
This phase I/II trial evaluated the maximum tolerated doses (MTD), safety and efficacy of pomalidomide, bortezomib and dexamethasone (PVD) combination in patients with relapsed, lenalidomide refractory, MM. In the phase I, dose level 1 consisted of pomalidomide 4mg PO days 1-21, bortezomib 1.0 mg/m(2) IV or SQ days 1,8,15,22 and dexamethasone 40mg PO days 1,8,15,22 given every 28 days. Bortezomib was increased to 1.3 mg/m(2) for dose level 2 and adopted in the phase 2 expansion cohort. We describe the results of 50 patients...
July 6, 2017: Blood
https://www.readbyqxmd.com/read/28679737/how-i-treat-first-relapse-of-myeloma
#4
Jean Luc Harousseau, Michel Attal
The standard treatment of relapsed multiple myeloma (MM) was either lenalidomide-dexamethasone (RD) or bortezomib-dexamethasone (VD) but it is changing rapidly for two reasons. Firstly lenalidomide and bortezomib are currently used in frontline treatment and many patients become resistant to these agents early in the course of their disease. Secondly six second-line new agents have been recently developed and offer new possibilities (pomalidomide, carfilzomib and ixazomib, panobinostat, elotuzumab and daratumumab)...
July 5, 2017: Blood
https://www.readbyqxmd.com/read/28670693/cxcl12-and-cxcr7-are-relevant-targets-to-reverse-cell-adhesion-mediated-drug-resistance-in-multiple-myeloma
#5
Johannes M Waldschmidt, Anna Simon, Dagmar Wider, Stefan J Müller, Marie Follo, Gabriele Ihorst, Sarah Decker, Joschka Lorenz, Manik Chatterjee, Abdel K Azab, Justus Duyster, Ralph Wäsch, Monika Engelhardt
Cell adhesion-mediated drug resistance (CAM-DR) by the bone marrow (BM) is fundamental to multiple myeloma (MM) propagation and survival. Targeting BM protection to increase the efficacy of current anti-myeloma treatment has not been extensively pursued. To extend the understanding of CAM-DR, we hypothesized that the cytotoxic effects of novel anti-myeloma agents may be abrogated by the presence of BM stroma cells (BMSCs) and restored by addition of the CXCL12 antagonist NOX-A12 or the CXCR4 inhibitor plerixafor...
July 2, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28642620/pomalidomide-bortezomib-and-low-dose-dexamethasone-in-lenalidomide-refractory-and-proteasome-inhibitor-exposed-myeloma
#6
P G Richardson, C C Hofmeister, N S Raje, D S Siegel, S Lonial, J Laubach, Y A Efebera, D H Vesole, A K Nooka, J Rosenblatt, D Doss, M H Zaki, A Bensmaine, J Herring, Y Li, L Watkins, M S Chen, K C Anderson
This phase 1 dose-escalation study evaluated pomalidomide, bortezomib (subcutaneous (SC) or intravenous (IV)) and low-dose dexamethasone (LoDEX) in lenalidomide-refractory and proteasome inhibitor-exposed relapsed or relapsed and refractory multiple myeloma (RRMM). In 21-day cycles, patients received pomalidomide (1-4 mg days 1-14), bortezomib (1-1.3 mg/m(2) days 1, 4, 8 and 11 for cycles 1-8; days 1 and 8 for cycle ⩾9) and LoDEX. Primary endpoint was to determine the maximum tolerated dose (MTD). Thirty-four patients enrolled: 12 during escalation, 10 in the MTD IV bortezomib cohort and 12 in the MTD SC bortezomib cohort...
June 2, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28637662/daratumumab-plus-pomalidomide-and-dexamethasone-in-relapsed-and-or-refractory-multiple-myeloma
#7
Ajai Chari, Attaya Suvannasankha, Joseph W Fay, Bertrand Arnulf, Jonathan L Kaufman, Jainulabdeen J Ifthikharuddin, Brendan M Weiss, Amrita Krishnan, Suzanne Lentzsch, Raymond Comenzo, Jianping Wang, Kerri Nottage, Christopher Chiu, Nushmia Z Khokhar, Tahamtan Ahmadi, Sagar Lonial
Daratumumab plus pomalidomide/dexamethasone (pom-dex) was evaluated in patients with relapsed/refractory multiple myeloma with ≥2 prior lines of therapy, and who were refractory to their last treatment. Patients received daratumumab 16 mg/kg at the recommended dosing schedule, pomalidomide 4 mg daily for 21 days of each 28-day cycle, and dexamethasone 40 mg weekly. Safety was the primary endpoint. Overall response rate (ORR) and minimal residual disease (MRD) by next-generation sequencing were secondary endpoints...
June 21, 2017: Blood
https://www.readbyqxmd.com/read/28620163/natural-history-of-relapsed-myeloma-refractory-to-immunomodulatory-drugs-and-proteasome-inhibitors-a-multicenter-imwg-study
#8
S K Kumar, M A Dimopoulos, E Kastritis, E Terpos, H Nahi, H Goldschmidt, J Hillengass, X Leleu, M Beksac, M Alsina, A Oriol, M Cavo, E M Ocio, M V Mateos, E K O'Donnell, R Vij, H M Lokhorst, N W C J van de Donk, C Min, T Mark, I Turesson, M Hansson, H Ludwig, S Jagannath, M Delforge, C Kyriakou, P Hari, U Mellqvist, S Z Usmani, D Dytfeld, A Z Badros, P Moreau, K Kim, P R Otero, J H Lee, C Shustik, D Waller, W J Chng, S Ozaki, J-J Lee, J de la Rubia, H S Eom, L Rosinol, J J Lahuerta, A Sureda, J S Kim, B G M Durie
Introduction of new myeloma therapies offers new options for patients refractory to immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs). In this multicenter study, patients with relapsed multiple myeloma, who have received at least three prior lines of therapy, are refractory to both an IMiD (lenalidomide or pomalidomide) and a PI (bortezomib or carfilzomib), and have been exposed to an alkylating agent were identified. The time patients met the above criteria was defined as time zero (T0). Five hundred and forty-three patients diagnosed between 2006 and 2014 were enrolled in this study...
May 12, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28601492/new-agents-in-multiple-myeloma-an%C3%A2-examination-of-safety-profiles
#9
REVIEW
Sara Bringhen, Edwin De Wit, Meletios-Athanassios Dimopoulos
Numerous treatments are available for relapsed and/or refractory multiple myeloma (MM), with safety profiles varying across drug classes and across agents within the same class. Thus, it is important to understand the toxicities of each antimyeloma agent when making treatment decisions. Neutropenia is commonly associated with lenalidomide and pomalidomide, and may be common with histone deacetylase (HDAC) inhibitors, but is relatively unusual with thalidomide, bortezomib, and carfilzomib. Infection was common in trials of lenalidomide and pomalidomide, and upper respiratory tract infection and pneumonia have been seen with carfilzomib...
May 10, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28591700/restoration-of-immune-surface-molecules-in-kaposi-sarcoma-associated-herpesvirus-infected-cells-by-lenalidomide-and-pomalidomide
#10
David A Davis, Suraj Mishra, Holda A Anagho, Ashley I Aisabor, Prabha Shrestha, Victoria Wang, Yuki Takamatsu, Kenji Maeda, Hiroaki Mitsuya, Jerome B Zeldis, Robert Yarchoan
Kaposi sarcoma-associated herpesvirus (KSHV) is the cause of several tumors, including Kaposi sarcoma and primary effusion lymphoma (PEL). Most viruses have evolved means of escaping immune recognition. KSHV downregulates MHC-I expression during lytic infection, and expression of ICAM-1 and B7-2 (CD86) during latent infection, allowing evasion of T cell and natural killer immunity respectively. These effects are largely mediated by two KSHV-encoded proteins, K3 and K5. We show here that lenalidomide (Len) and pomalidomide (Pom) prevent down-regulation of MHC-I during lytic activation, and restore ICAM-1 and B7-2 surface expression in latently infected PEL cells...
May 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28583668/-pomalidomide-for-multiple-myeloma
#11
Aurore Dougé, Richard Lemal, Carine Chaleteix
Pomalidomide is a second-generation immunomodulatory drug (IMID). Its efficiency overtakes its predecessors' (thalidomide, lenalidomide), with less toxicity. It is indicated in the treatment of refractory or relapsed multiple myeloma, associated to dexamethasone. It is available in France since 2013, following the results of different studies.
June 2, 2017: Bulletin du Cancer
https://www.readbyqxmd.com/read/28581522/blockade-of-deubiquitylating-enzyme-rpn11-triggers-apoptosis-in-multiple-myeloma-cells-and-overcomes-bortezomib-resistance
#12
Y Song, S Li, A Ray, D S Das, J Qi, M K Samur, Y-T Tai, N Munshi, R D Carrasco, D Chauhan, K C Anderson
Proteasome inhibition is an effective therapy for multiple myeloma (MM) patients; however, the emergence of drug resistance is common. Novel therapeutic strategies to overcome proteasome inhibitor resistance are needed. In this study, we examined whether targeting deubiquitylating (DUB) enzymes upstream of 20S proteasome overcomes proteasome inhibitor resistance. Gene expression analysis, immunohistochemical studies of MM patient bone marrow, reverse transcription-PCR and protein analysis show that Rpn11/POH1, a DUB enzyme upstream of 20S proteasome, is more highly expressed in patient MM cells than in normal plasma cells...
June 5, 2017: Oncogene
https://www.readbyqxmd.com/read/28530236/psilac-mass-spectrometry-reveals-zfp91-as-imid-dependent-substrate-of-the-crl4-crbn-ubiquitin-ligase
#13
Jian An, Charles M Ponthier, Ragna Sack, Jan Seebacher, Michael B Stadler, Katherine A Donovan, Eric S Fischer
Thalidomide and its derivatives lenalidomide and pomalidomide (IMiDs) are effective treatments of haematologic malignancies. It was shown that IMiDs impart gain-of-function properties to the CUL4-RBX1-DDB1-CRBN (CRL4(CRBN)) ubiquitin ligase that enable binding, ubiquitination and degradation of key therapeutic targets such as IKZF1, IKZF3 and CSNK1A1. While these substrates have been implicated as efficacy targets in multiple myeloma (MM) and 5q deletion associated myelodysplastic syndrome (del(5q)-MDS), other targets likely exist...
May 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/28529311/spotlight-on-pomalidomide-could-less-be-more
#14
T J Zander, S Aebi, T Pabst, C Renner, C Driessen
Leukemia accepted article preview online, 22 May 2017. doi:10.1038/leu.2017.156.
May 22, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28504846/adverse-event-management-in-patients-with-relapsed-and-refractory-multiple-myeloma-taking-pomalidomide-plus-low-dose-dexamethasone-a-pooled-analysis
#15
Philippe Moreau, Meletios A Dimopoulos, Paul G Richardson, David S Siegel, Michele Cavo, Paolo Corradini, Katja Weisel, Michel Delforge, Peter O'Gorman, Kevin Song, Christine Chen, Nizar Bahlis, Albert Oriol, Markus Hansson, Martin Kaiser, Pekka Anttila, Reinier Raymakers, Cristina Joao, Gordon Cook, Lars Sternas, Tsvetan Biyukov, Ana Slaughter, Kevin Hong, Jennifer Herring, Xin Yu, Mohamed Zaki, Jesus San-Miguel
OBJECTIVES: Heavily pretreated patients with relapsed and refractory multiple myeloma are susceptible to treatment-related adverse events (AEs). Managing AEs is important to ensure patients continue therapy long enough to receive the best clinical benefit. Data from the MM-002, MM-003, and MM-010 trials were pooled to further characterize the safety profile of pomalidomide plus low-dose dexamethasone and AE management. METHODS: This analysis included 1088 patients who received ≥ 2 prior therapies, including lenalidomide and bortezomib, and progressed ≤ 60 days of last therapy...
May 15, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28504554/how-is-patient-care-for-multiple-myeloma-advancing
#16
REVIEW
Sonja Genadieva Stavric, Francesca Bonello, Sara Bringhen, Mario Boccadoro, Alessandra Larocca
Treatment of multiple myeloma has undergone profound changes in the past years thanks to the increased understanding of the biology of the disease and the new treatment options. New drugs and effective approaches are currently available for the treatment of multiple myeloma, including immunomodulatory agents, proteasome inhibitors and autologous stem cell transplantation. Areas covered: We have described the recent updated criteria to start treatment in multiple myeloma and summarized clinical data from major studies including most recent agents...
June 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28479592/a-novel-agent-sl-401-induces-anti-myeloma-activity-by-targeting-plasmacytoid-dendritic-cells-osteoclastogenesis-and-cancer-stem-like-cells
#17
A Ray, D S Das, Y Song, V Macri, P Richardson, C L Brooks, D Chauhan, K C Anderson
Novel therapies for multiple myeloma (MM) can target mechanism(s) in the host-MM bone marrow (BM) microenvironment mediating MM progression and chemoresistance. Our studies showed increased numbers of tumor-promoting, immunosuppressive, and drug-resistant plasmacytoid dendritic cells (pDCs) in the MM BM microenvironment. pDC-MM cell interactions upregulate interleukin-3 (IL-3), which stimulates both pDC survival and MM cell growth. Since IL-3R is highly expressed on pDCs in the MM BM milieu, we here targeted pDCs using a novel IL-3R-targeted therapeutic SL-401...
May 8, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28474745/daratumumab-monotherapy-compared-with-historical-control-data-in-heavily-pretreated-and-highly-refractory-patients-with-multiple-myeloma-an-adjusted-treatment-comparison
#18
Saad Z Usmani, Joris Diels, Tetsuro Ito, Maneesha Mehra, Imran Khan, Annette Lam
Daratumumab is a human CD38-directed monoclonal antibody approved in the United States as monotherapy for patients with multiple myeloma (MM) who have received ≥3 prior lines of therapy (LOTs), including a proteasome inhibitor (PI) and an immunomodulatory agent (IMiD) or who are double refractory to a PI and an IMiD, and in combination with lenalidomide/dexamethasone or bortezomib/dexamethasone for patients with MM who have received ≥1 prior LOT. This study compared the efficacy of daratumumab monotherapy versus historical controls through adjusted treatment comparison...
May 5, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28465517/a-randomized-study-of-pomalidomide-vs-placebo-in-persons-with-myeloproliferative-neoplasm-associated-myelofibrosis-and-rbc-transfusion-dependence
#19
A Tefferi, H K Al-Ali, G Barosi, T Devos, H Gisslinger, Q Jiang, J-J Kiladjian, R Mesa, F Passamonti, M F McMullin, V Ribrag, G Schiller, A M Vannucchi, D Zhou, D Reiser, J Zhong, R P Gale
No abstract text is available yet for this article.
May 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28461396/pembrolizumab-pomalidomide-and-low-dose-dexamethasone-for-relapsed-refractory-multiple-myeloma
#20
Ashraf Badros, Elizabeth Hyjek, Ning Ma, Alexander Lesokhin, Ahmet Dogan, Aaron P Rapoport, Mehmet Kocoglu, Emily Lederer, Sunita Philip, Todd Milliron, Cameron Dell, Olga Goloubeva, Zeba Singh
Programmed death 1 (PD-1) receptor and its ligand (PD-L1) facilitate immune evasion in multiple myeloma (MM). We hypothesized that pembrolizumab, PD-1-antibody, can enhance anti-myeloma cellular immunity generated by pomalidomide leading to improved clinical responses. In this single-center, phase II study, 48 patients with relapsed/refractory MM (RRMM) received 28-days cycles of pembrolizumab, 200 mg intravenously every 2 weeks, pomalidomide 4 mg daily for 21 days and dexamethasone 40 mg weekly. Patients had a median of 3 (range: 2-5) lines of therapy, median age 64 (range: 35-83) years and had received both immune modulatory agent and proteasome inhibitor; (35 [73%] of 48) were refractory to both; (31 [70%]) had received an autologous transplant and (30 [62%]) had high-risk cytogenetics...
May 1, 2017: Blood
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