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https://www.readbyqxmd.com/read/29776381/wnt-signaling-in-multiple-myeloma-a-central-player-in-disease-with-therapeutic-potential
#1
REVIEW
Ingrid Spaan, Reinier A Raymakers, Anja van de Stolpe, Victor Peperzak
Multiple myeloma is the second most frequent hematological malignancy in the western world and remains incurable, predominantly due to acquired drug resistance and disease relapse. The highly conserved Wnt signal transduction pathway, which plays a key role in regulating cellular processes of proliferation, differentiation, migration, and stem cell self-renewal, is associated with multiple aspects of disease. Bone homeostasis is severely disturbed by Wnt antagonists that are secreted by the malignant plasma cells in the bone marrow...
May 18, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29760659/long-term-efficacy-of-maintenance-therapy-for-multiple-myeloma-a-quantitative-synthesis-of-22-randomized-controlled-trials
#2
Jie-Li Li, Guang-Yu Fan, Yu-Jie Liu, Zi-Hang Zeng, Jing-Juan Huang, Zong-Ming Yang, Xiang-Yu Meng
We aimed to quantitatively synthesize data from randomized controlled trials (RCTs) concerning maintenance for multiple myeloma (MM). We searched electronic literature databases and conference proceedings to identify relevant RCTs. We selected eligible RCTs using predefined selection criteria. We conducted meta-analysis comparing maintenance containing new agents and conventional maintenance, and subgroup analysis by transplantation status and mainstay agent as well. We performed trial sequential analysis (TSA) to determine adequacy of sample size for overall and subgroup meta-analyses...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29756564/clinical-and-pharmacologic-features-of-monoclonal-antibodies-and-checkpoint-blockade-therapy-in-multiple-myeloma
#3
Mattia D'Agostino, Giulia Gazzera, Giusy Cetani, Sara Bringhen, Mario Boccadoro, Francesca Gay
BACKGROUND: Survival of multiple myeloma patients has considerably improved in the last decades thanks to the introduction of many new drugs, including immunomodulatory agents, proteasome inhibitors and, more recently, monoclonal antibodies. METHODS: We analyzed the most recent literature focusing on the clinical and pharmacologic aspects of monoclonal antibody-based therapies in multiple myeloma, including monoclonal antibodies directed against plasma cell antigens, as well as checkpoint blockade therapy directed against immune inhibitory molecules, used as single agents or in combination therapy...
May 13, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29756171/real-world-data-on-len-dex-combination-at-second-line-therapy-of-multiple-myeloma-treatment-at-biochemical-relapse-is-a-significant-prognostic-factor-for-progression-free-survival
#4
Eirini Katroditou, Marie-Christine Kyrtsonis, Sosana Delimpasi, Despoina Kyriakou, Argiris Symeonidis, Emmanouil Spanoudakis, Georgios Vasilopoulos, Achilles Anagnostopoulos, Anna Kioumi, Panagiotis Zikos, Anthi Aktypi, Evangelos Briasoulis, Aikaterini Megalakaki, Panayiotis Repousis, Ioannis Adamopoulos, Dimitrios Gogos, Maria Kotsopoulou, Vassiliki Pappa, Eleni Papadaki, Despoina Fotiou, Eftychia Nikolaou, Evlambia Giannopoulou, Eleftheria Hatzimichael, Nikolaos Giannakoulas, Vassiliki Douka, Kyriaki Kokoviadou, Despoina Timotheatou, Evangelos Terpos
We evaluated progression-free survival (PFS) rate of patients treated with lenalidomide/dexamethasone (Len/Dex), the efficacy of the combination, and the prognostic significance of treatment at biochemical vs. clinical relapse on PFS in 207 consecutive myeloma patients treated with Len/Dex in second line, according to routine clinical practice in Greece. First-line treatment included bortezomib-based (63.3%) or immunomodulatory drug-based (34.8%) therapies; 25% of patients underwent autologous stem cell transplantation...
May 13, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29755699/sequential-immunotherapy-in-a-patient-with-primary-refractory-hodgkin-lymphoma-and-novel-mutations
#5
Richard Greil, Lisa Pleyer, Bettina Jansko, Carmen Feierabend, Lukas Rettenbacher, Olga Stiefel, Christoph Rass, Patrick Morre, Daniel Neureiter, Sigrun Greil-Ressler
Primary resistant Hodgkin lymphoma is an aggressive disease with few treatment options and short survival. Neoplastic cells of classical Hodgkin lymphoma are heavily dependent on microenvironmental stimuli, regularly express PD-L1, and a relevant proportion of relapsed patients is sensitive to blocking of the PD1/PD-L1 axis. However, response duration is limited and further treatment options are unknown but urgently needed. We report a case of a patient without relevant response to five subsequent chemotherapy regimens who immediately and dramatically responded to an anti-PD1 mab...
April 17, 2018: Oncotarget
https://www.readbyqxmd.com/read/29755672/inhibition-of-mtor-complex-2-restrains-tumor-angiogenesis-in-multiple-myeloma
#6
Aurelia Lamanuzzi, Ilaria Saltarella, Vanessa Desantis, Maria Antonia Frassanito, Patrizia Leone, Vito Racanelli, Beatrice Nico, Domenico Ribatti, Paolo Ditonno, Marcella Prete, Antonio Giovanni Solimando, Francesco Dammacco, Angelo Vacca, Roberto Ria
The mammalian Target of Rapamycin (mTOR) is an intracellular serine/threonine kinase that mediates intracellular metabolism, cell survival and actin rearrangement. mTOR is made of two independent complexes, mTORC1 and mTORC2, activated by the scaffold proteins RAPTOR and RICTOR, respectively. The activation of mTORC1 triggers protein synthesis and autophagy inhibition, while mTORC2 activation promotes progression, survival, actin reorganization, and drug resistance through AKT hyper-phosphorylation on Ser473...
April 17, 2018: Oncotarget
https://www.readbyqxmd.com/read/29755666/impact-of-lenalidomide-maintenance-on-the-immune-environment-of-multiple-myeloma-patients-with-low-tumor-burden-after-autologous-stem-cell-transplantation
#7
Karel Fostier, Jo Caers, Nathalie Meuleman, Katrijn Broos, Jurgen Corthals, Kris Thielemans, Rik Schots, Brenda De Keersmaecker
Lenalidomide is a potent anti-myeloma drug with immunomodulatory properties. It is increasingly used in a low-dose maintenance setting to prolong remission duration after standard treatment. Data on the in vivo effects of lenalidomide are scarce and sometimes different from the well-described in vitro effects. We therefore evaluated the numerical, phenotypical and functional impact of lenalidomide maintenance on several immune cell types in a cohort of seventeen homogeneously treated myeloma patients achieving a low residual myeloma burden after a bortezomib based-induction followed by autologous stem cell transplantation...
April 17, 2018: Oncotarget
https://www.readbyqxmd.com/read/29753690/successful-use-of-bortezomib-lenalidomide-combination-as-treatment-for-a-patient-with-plasmablastic-lymphoma
#8
William D Marrero, Alexis Cruz-Chacón, Christian Castillo, Fernando Cabanillas
No abstract text is available yet for this article.
May 4, 2018: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29746861/lenalidomide-regulates-osteocytes-fate-and-related-osteoclastogenesis-via-il-1%C3%AE-nf-%C3%AE%C2%BAb-rankl-signaling
#9
Xinhua Qu, Jingtian Mei, Zhifeng Yu, Zanjing Zhai, Han Qiao, Kerong Dai
Osteolytic diseases are closely associated with osteocyte fate, indicating a more efficient and crucial role of osteocyte-targeting strategy in inhibiting osteoclastogenesis. Here, we investigated the effects of lenalidomide (Lena) on osteocyte fate in order to regulate osteoclastogenesis via effective cascade-controlling response. Our data revealed that lenalidomide treatment notably rescued IL-1β induced loss of osteocyte viability by inhibiting osteocyte apoptosis with decreased osteoclast-related factors, RANKL and Sclerostin, as demonstrated by the restricted osteoclast formation and reduced bone resorption...
May 7, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29744077/hyperbilirubinemia-following-lenalidomide-administration
#10
Veronica Azmy, Natalia Neparidze
Asymptomatic hyperbilirubinemia in a patient with no underlying liver disease or renal impairment while on lenalidomide therapy may be attributable to the unmasking of previously undiagnosed Gilbert's syndrome, as previously shown in the literature. The hyperbilirubinemia should resolve after discontinuation of the drug.
May 2018: Clinical Case Reports
https://www.readbyqxmd.com/read/29743398/-achievement-of-a-stringent-complete-response-with-low-dose-pomalidomide-monotherapy-in-a-multiple-myeloma-patient
#11
Toshihide Endo, Takashi Hamada, Shimon Otake, Masaru Nakagawa, Yshihito Uchino, Hiromichi Takahashi, Katsuhiro Miura, Noriyoshi Iriyama, Takashi Koike, Kazuya Kurihara, Hiroko Sato, Yoshihiro Hatta, Msamai Takei
An 80-year-old man presented to our hospital with a thoracic vertebrae compression fracture. He was diagnosed with IgG-λ myeloma (International Staging System stage II, Durie-Salmon stage IIIA). Since melphalan-prednisolone (MP) was not effective, we treated him with lenalidomide and low-dose dexamethasone (DEX) (Ld), achieving a partial response. As DEX provoked edema and psychiatric symptoms, the patient disagreed with its use, and pomalidomide (POM) monotherapy was initiated. Although the POM dosage was reduced to 1-2 mg/day due to somnolence, which was reported as an adverse event, stringent complete response (sCR) was achieved and sustained for 10 months following 11 cycles of low-dose POM monotherapy...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/29741409/healthcare-resource-utilization-with-ixazomib-or-placebo-plus-lenalidomide-dexamethasone-in-the-randomized-double-blind-phase-3-tourmaline-mm1-study-in-relapsed-refractory-multiple-myeloma
#12
Parameswaran Hari, Huamao Mark Lin, Yanyan Zhu, Deborah Berg, Paul G Richardson, Philippe Moreau
AIMS: The aim of this analysis was to assess healthcare resource utilization in the pivotal phase 3 TOURMALINE-MM1 study of the oral proteasome inhibitor ixazomib or placebo plus lenalidomide and dexamethasone (Rd) in relapsed and/or refractory multiple myeloma (RRMM). METHODS: In this double-blind, placebo-controlled, randomized study (NCT01564537), 722 patients with RRMM following 1-3 prior lines of therapy received Rd plus ixazomib (ixazomib-Rd; N = 360) or matching placebo (placebo-Rd; N = 362) until disease progression or unacceptable toxicity...
May 9, 2018: Journal of Medical Economics
https://www.readbyqxmd.com/read/29740809/a-phase-2-study-of-modified-lenalidomide-bortezomib-and-dexamethasone-in-transplant-ineligible-multiple-myeloma
#13
Elizabeth K O'Donnell, Jacob P Laubach, Andrew J Yee, Tianqi Chen, Carol Ann Huff, Frank G Basile, Philip M Wade, Claudia E Paba-Prada, Irene M Ghobrial, Robert L Schlossman, Jill N Burke, Cynthia C Harrington, Kathleen J Lively, Hannah F Lyons, Nikhil C Munshi, Kenneth C Anderson, Lorenzo Trippa, Paul G Richardson, Noopur S Raje
We sought a regimen that incorporates optimal novel agents and balances efficacy with toxicity in transplant-ineligible multiple myeloma (MM) patients. Our study evaluated modified lenalidomide-bortezomib-dexamethasone (RVD lite) in this population and was administered over a 35-day cycle. Lenalidomide 15 mg was given orally on days 1-21; bortezomib 1·3 mg/m2 weekly subcutaneously on days 1, 8, 15 and 22; and dexamethasone 20 mg orally was given on the day of and day after bortezomib for 9 cycles followed by 6 cycles of consolidation with lenalidomide and bortezomib...
May 8, 2018: British Journal of Haematology
https://www.readbyqxmd.com/read/29731882/autologous-stem-cell-transplantation-in-ebv-positive-post-renal-transplant-refractory-multiple-myeloma-a-case-report-and-literature-review
#14
Xiaobao Xie, Yan Lin, Yang Cao, Weimin Dong, Wei Wu, Yuandong Zhu, Deliang Liu, Haiqian Li, Qing Li, Weiying Gu
Renal transplant recipients exhibit an increased risk of developing plasma cell neoplasms (PCNs; comprising multiple myeloma and plasmacytoma); however, multiple myeloma manifesting with refractory extramedullary plasmacytomas associated with Epstein-Barr virus are markedly rare in these patients. In the present case report, an unusual case of refractory multiple myeloma with multiple extramedullary plasmacytoma (including liver, vertebrae, breast, muscle, skin and soft tissues) was presented. The patient exhibited mild bone marrow infiltration which was successfully treated with novel agents, including bortezomib and lenalidomide, followed by autologous stem cell transplantation (ASCT)...
May 2018: Oncology Letters
https://www.readbyqxmd.com/read/29728700/combination-therapy-with-carfilzomib-lenalidomide-and-dexamethasone-krd-results-in-an-unprecedented-purity-of-the-stem-cell-graft-in-newly-diagnosed-patients-with-myeloma
#15
Nishant Tageja, Neha Korde, Dickran Kazandjian, Sandhya Panch, Elisabet Manasanch, Manisha Bhutani, Mary Kwok, Sham Mailankody, Constance Yuan, Maryalice Stetler-Stevenson, Susan F Leitman, Claude Sportes, Ola Landgren
Still, many physicians give 4 cycles of combination therapy to multiple myeloma patients prior to collection of stem cells for autologous bone marrow transplant. This tradition originates from older doxorubicin-containing regiments which limited the number of cycles due to cumulative cardiotoxicity. Using older regiments, most patients had residual myeloma cells in their autologous stem-cell grafts during collection. Emerging data show that newly diagnosed multiple myeloma patients treated with modern carfilzomib/lenalidomide/dexamethasone (KRd) therapy, on average, take 6 cycles until reaching minimal residual disease (MRD) negativity...
May 4, 2018: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/29726031/patient-reported-health-related-quality-of-life-from-the-phase-iii-tourmaline-mm1-study-of-ixazomib-lenalidomide-dexamethasone-versus-placebo-lenalidomide-dexamethasone-in-relapsed-refractory-multiple-myeloma
#16
Xavier Leleu, Tamas Masszi, Nizar J Bahlis, Luisa Viterbo, Bartrum Baker, Peter Gimsing, Vladimir Maisnar, Olga Samoilova, Laura Rosiñol, Christian Langer, Kevin Song, Tohru Izumi, Charles Cleeland, Deborah Berg, Huamao Mark Lin, Yanyan Zhu, Tomas Skacel, Philippe Moreau, Paul G Richardson
TOURMALINE-MM1 is a phase III, randomized, double-blind, placebo-controlled study of ixazomib plus lenalidomide and dexamethasone (IRd) versus placebo-Rd in patients with relapsed/refractory multiple myeloma following 1-3 prior lines of therapy. The study met its primary endpoint, demonstrating significantly longer progression-free survival (PFS) in the IRd arm versus placebo-Rd arm (median 20.6 vs 14.7 months, hazard ratio 0.74, P = 0.01), with limited additional toxicity. Patient-reported health-related quality of life (HRQoL) was a secondary endpoint of TOURMALINE-MM1...
May 4, 2018: American Journal of Hematology
https://www.readbyqxmd.com/read/29719938/cyclophosphamide-s-addition-in-relapsed-refractory-multiple-myeloma-patients-with-biochemical-progression-during-lenalidomide-dexamethasone-treatment
#17
Laura Cesini, Agostina Siniscalchi, Sara Grammatico, Alessandro Andriani, Alessia Fiorini, Luca De Rosa, Tommaso Za, Angela Rago, Tommaso Caravita, Maria Teresa Petrucci
OBJECTIVE: The aim of this study was to evaluate the addition of Cyclophosphamide in relapsed-refractory Multiple Myeloma patients (RRMM) who experienced biochemical relapse or progression without CRAB, during treatment with Lenalidomide and Dexamethasone (Rd), to slow down the progression in active relapse. METHODS: This analysis included 31 patients with RRMM treated with Rd who received cyclophosphamide (CRd) at biochemical relapse. The CRd regimen was continued until disease progression...
May 2, 2018: European Journal of Haematology
https://www.readbyqxmd.com/read/29718735/expression-of-crbn-ikzf1-and-ikzf3-does-not-predict-lenalidomide-sensitivity-and-mutations-in-the-cereblon-pathway-are-infrequent-in-multiple-myeloma
#18
Konstantinos Dimopoulos, Helga Fibiger Munch-Petersen, Christian Winther Eskelund, Lene Dissing Sjö, Elisabeth Ralfkiaer, Peter Gimsing, Kirsten Grønbaek
The immunomodulatory drug thalidomide, and its analogs, lenalidomide, and pomalidomide (IMiDs), have become essential components of the standard treatment for multiple myeloma (MM), and have led to significant improvement of survival in patients with this devastating disease. Cereblon (CRBN), the direct target of IMiDs, has been proposed as a predictive biomarker of response to IMiDs. Using standard immunohistochemistry in formalin-fixed paraffin embedded (FFPE) bone marrow samples of 23 patients treated with a lenalidomide-containing regimen, we found that the malignant plasma cells of all the patients stained positive for CRBN, IKZF1, and IKZF3, regardless of sensitivity to IMiDs...
May 2, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29712909/widespread-intronic-polyadenylation-diversifies-immune-cell-transcriptomes
#19
Irtisha Singh, Shih-Han Lee, Adam S Sperling, Mehmet K Samur, Yu-Tzu Tai, Mariateresa Fulciniti, Nikhil C Munshi, Christine Mayr, Christina S Leslie
Alternative cleavage and polyadenylation (ApA) is known to alter untranslated region (3'UTR) length but can also recognize intronic polyadenylation (IpA) signals to generate transcripts that lose part or all of the coding region. We analyzed 46 3'-seq and RNA-seq profiles from normal human tissues, primary immune cells, and multiple myeloma (MM) samples and created an atlas of 4927 high-confidence IpA events represented in these cell types. IpA isoforms are widely expressed in immune cells, differentially used during B-cell development or in different cellular environments, and can generate truncated proteins lacking C-terminal functional domains...
April 30, 2018: Nature Communications
https://www.readbyqxmd.com/read/29712896/daratumumab-lenalidomide-and-dexamethasone-in-east-asian-patients-with-relapsed-or-refractory-multiple-myeloma-subgroup-analyses-of-the-phase-3-pollux-study
#20
Kenshi Suzuki, Meletios A Dimopoulos, Naoki Takezako, Shinichiro Okamoto, Atsushi Shinagawa, Morio Matsumoto, Hiroshi Kosugi, Sung-Soo Yoon, Shang-Yi Huang, Xiang Qin, Ming Qi, Shinsuke Iida
In the phase 3 POLLUX study, daratumumab plus lenalidomide and dexamethasone (DRd) significantly reduced the risk of progression/death and induced deeper responses vs. lenalidomide and dexamethasone alone (Rd) in patients with relapsed/refractory multiple myeloma (RRMM). We report a subgroup analysis of East Asian (Japanese, Korean, and Taiwanese) patients from POLLUX based on a longer follow-up of 24.7 months. Median progression-free survival was not reached (NR) for DRd vs. 13.8 months for Rd (hazard ratio [HR], 0...
May 1, 2018: Blood Cancer Journal
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