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Lenalidomide

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https://www.readbyqxmd.com/read/29155440/severe-hypoglycemia-caused-by-lenalidomide
#1
Daniel J Przybylski, Ruemu Birhiray, David J Reeves
Lenalidomide is commonly used for multiple myeloma as either induction or maintenance therapy. The agent is associated with a host of adverse effects, but hypoglycemia has only been reported in one phase I trial in patients with solid tumors. We describe a 74-year-old woman who experienced grade 3 hypoglycemia (blood glucose level 35 mg/dL) likely related to lenalidomide. Her medical history was significant for refractory myeloma and type 2 diabetes mellitus. Lenalidomide was started as maintenance therapy following autologous bone marrow transplantation...
November 20, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/29150421/final-analysis-of-survival-outcomes-in-the-randomized-phase-3-first-trial
#2
Thierry Facon, Meletios A Dimopoulos, Angela Dispenzieri, John V Catalano, Andrew Belch, Michele Cavo, Antonello Pinto, Katja Weisel, Heinz Ludwig, Nizar J Bahlis, Anne Banos, Mourad Tiab, Michel Delforge, Jamie D Cavenagh, Catarina Geraldes, Je-Jung Lee, Christine Chen, Albert Oriol, Javier De La Rubia, Darell White, Daniel Binder, Jin Lu, Kenneth C Anderson, Philippe Moreau, Michel Attal, Aurore Perrot, Bertrand Arnulf, Lugui Qiu, Murielle Roussel, Eileen Boyle, Salomon Manier, Mohamad Mohty, Herve Avet-Loiseau, Xavier Leleu, Annette Ervin-Haynes, Guang Chen, Vanessa Houck, Lotfi Benboubker, Cyrille Hulin
This FIRST trial final analysis examined survival outcomes in patients with transplant-ineligible newly diagnosed multiple myeloma (NDMM) treated with lenalidomide and low-dose dexamethasone until disease progression (Rd continuous), Rd for 72 weeks (18 cycles; Rd18), or melphalan, prednisone, and thalidomide (MPT; 72 weeks). The primary endpoint was progression-free survival (PFS; primary comparison: Rd continuous vs MPT). Overall survival (OS) was a key secondary endpoint (final analysis prespecified ≥ 60 months' follow-up)...
November 17, 2017: Blood
https://www.readbyqxmd.com/read/29137233/outcome-of-patients-treated-for-myelodysplastic-syndromes-with-5q-deletion-after-failure-of-lenalidomide-therapy
#3
Thomas Prebet, Thomas Cluzeau, Sophie Park, Mikkael A Sekeres, Ulrich Germing, Lionel Ades, Uwe Platzbecker, Katharina Gotze, Norbert Vey, Esther Oliva, Mary M Sugrue, Cecile Bally, Charikleia Kelaidi, Najla Al Ali, Pierre Fenaux, Steven D Gore, Rami Komrokji
While lenalidomide (LEN) is the standard of care for the lower-risk myelodysplastic syndromes (MDS) patients with deletion 5q, 35% will not respond to or do not tolerate the drug. Moreover, most of the patients will lose their response after a few years. Defining the outcome of patients with LEN failure and determining the impact of subsequent therapies is therefore important to develop alternative strategies. Based on an international collaboration, we were able to compile a total of 392 patient cases of lower-risk MDS patients with 5q deletion and to analyze their outcome after failure of lenalidomide...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29136724/-expert-consensus-for-the-diagnosis-and-treatment-of-patients-with-renal-impairment-of-multiple-myeloma
#4
(no author information available yet)
Renal impairment (RI) is a common complication of multiple myeloma (MM), which is presented as chronic kidney disease (CKD) or acute kidney injury (AKI). The typical pathological feature is cast nephropathy. Presently international system staging (ISS) is used in evaluating MM. Although the classic Durie-Salmon staging system could be still used in clinical practice, it may miss out some patients with renal impairment. For evaluations of RI in MM patients with CKD, it's recommended to assess the estimated glomerular filtration rate (eGFR) by creatinine based formula CKD-epidemiology collaboration (EPI) or modification of diet in renal disease(MDRD) and to stage the renal injuries according to 2013 Kidney Disease Improving Global Outcomes (KDIGO) CKD guidelines...
November 1, 2017: Zhonghua Nei Ke za Zhi [Chinese Journal of Internal Medicine]
https://www.readbyqxmd.com/read/29134824/an-overview-of-the-role-of-carfilzomib-in-the-treatment-of-multiple-myeloma
#5
Dimitrios C Ziogas, Evangelos Terpos, Efstathios Kastritis, Meletios A Dimopoulos
Carfilzomib is a second-generation proteasome inhibitor that binds selectively and irreversibly with the chymotrypsin-like site of the proteolytic core. Its initial approval by the Food and Drug Administration, as monotherapy for relapsed/refractory multiple myeloma (RR-MM), followed soon by a global authorization of its combination with dexamethasone or with lenalidomide plus dexamethasone for the treatment of RR-MM after 1-3 prior lines. In order to optimize its administration, carfilzomib is currently examined in different doses and regimens in relapsed/refractory as well as in newly diagnosed myeloma...
November 14, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/29130642/dual-inhibition-of-dnmts-and-ezh2-can-overcome-both-intrinsic-and-acquired-resistance-of-myeloma-cells-to-imids-in-a-cereblon-independent-manner
#6
Konstantinos Dimopoulos, Alexandra Søgaard Helbo, Helga Fibiger Munch-Petersen, Lene Sjö, Jesper Christensen, Lasse Sommer Kristensen, Fazila Asmar, Emil Hermansen, Casey O'Connel, Peter Gimsing, Gangning Liang, Kirsten Grønbaek
Thalidomide and its derivatives, lenalidomide and pomalidomide (also known as IMiDs), have significantly changed the treatment landscape of multiple myeloma, and the recent discovery of cereblon (CRBN) as their direct biological target has led to a deeper understanding of their complex mechanism of action. In an effort to comprehend the precise mechanisms behind the development of IMiD resistance and examine whether it is potentially reversible, we established lenalidomide- (-LR) and pomalidomide-resistant (-PR) human myeloma cell lines from two IMiD-sensitive cell lines, OPM2 and NCI-H929, by continuous culture in the presence of lenalidomide or pomalidomide for 4-6 months, until acquirement of stable resistance...
November 11, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/29127751/-the-benefit-of-new-angiogenesis-bevacizumab-and-aflibercept-inhibitors-for-multiple-angiomatosis-therapy-a%C3%A2-case-report
#7
Dagmar Brančíková, Lenka Ostřížková, Zdeněk Adam, Tomáš Nebeský, Luděk Pour, Zdeněk Král, Jiří Mayer
Angiomatosis is a term for multiple, gradually proliferating hemangiomas (angiodysplasia), affecting multiple organs or tissues at the same time. We describe a 12-year course of treatment of a patient with multiple hemangiomas located in the abdomen, retroperitoneum, oesophagus, mediastinum and also in vertebrae. The diagnosis was made in 2005 within probatory laparotomy, at the age of 28 years. The treatment was commenced right after making the diagnosis with interferon α. Due to its adverse effects (fatigue, anorexia), the use of interferon α was limited to the first year, after which the interferon dose was gradually being reduced until it was discontinued completely...
2017: Vnitr̆ní Lékar̆ství
https://www.readbyqxmd.com/read/29127588/daratumumab-a-review-in-relapsed-and-or-refractory-multiple-myeloma
#8
Hannah A Blair
Intravenous daratumumab (DARZALEX(®)) is a first-in-class human IgG1κ monoclonal antibody against CD38 available for use in patients with relapsed and/or refractory multiple myeloma. In phase I/II and II trials and a pooled analysis of these studies, daratumumab monotherapy induced an overall response (partial response or better) in approximately one-third of patients; responses were rapid, deep and durable. An overall survival (OS) benefit was seen with daratumumab monotherapy, including in patients with a minimal response or stable disease...
November 10, 2017: Drugs
https://www.readbyqxmd.com/read/29126866/advances-in-diagnosis-and-management-of-diffuse-large-b-cell-lymphoma
#9
REVIEW
Fernando Cabanillas, Bijal Shah
The management of diffuse large B-cell lymphoma (DLBCL) has been gradually evolving since the discovery of its 2 major forms, the germinal center B-like (GCB) and activated B-cell (ABC) types. Although the reference standard for the identification of these cell types is considered gene expression profiling (GEP), currently the only method commercially available is immunohistochemistry (IHC). The application of various IHC-based algorithms and their correlation with GEP and clinical outcome are discussed. Because of the adverse prognostic implications of the non-GCB type and its potential effects on treatment selection, the recently revised World Health Organization classification has included these biologic cell types...
November 7, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29119643/a-phase-i-study-of-lenalidomide-plus-chemotherapy-with-mitoxantrone-etoposide-and-cytarabine-for-the-reinduction-of-patients-with-acute-myeloid-leukemia
#10
Daniel J DeAngelo, Andrew M Brunner, Lillian Werner, David Avigan, Amir T Fathi, Adam S Sperling, Abigail Washington, Dina Stroopinsky, Jacalyn Rosenblatt, Malgorzata McMasters, Katarina Luptakova, Martha Wadleigh, David P Steensma, Gabriela S Hobbs, Eyal C Attar, Philip C Amrein, Benjamin L Ebert, Richard M Stone, Karen K Ballen
Patients with relapsed AML have a poor prognosis and limited responses to standard chemotherapy. Lenalidomide is an immunomodulatory drug that may modulate anti-tumor immunity. We performed a study to evaluate the safety and tolerability of lenalidomide with mitoxantrone, etoposide and cytarabine (MEC) in relapsed/refractory AML. Adult patients with relapsed/refractory AML were eligible for this phase I dose-escalation study. We enrolled 35 patients using a '3 + 3' design, with a 10 patient expansion cohort at the maximum tolerated dose (MTD)...
November 9, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/29118268/azacitidine-in-lower-risk-myelodysplastic-syndromes-a-meta-analysis-of-data-from-prospective-studies
#11
Rami Komrokji, Arlene S Swern, David Grinblatt, Roger M Lyons, Magnus Tobiasson, Lewis R Silverman, Hamid Sayar, Ravi Vij, Albert Fliss, Nora Tu, Mary M Sugrue
BACKGROUND: After erythropoiesis-stimulating agent (ESA) failure, lenalidomide and hypomethylating agents are the only remaining treatment options for most patients with lower-risk myelodysplastic syndromes (LR-MDS). Optimal choice of these agents as front-line therapy in non-del(5q) LR-MDS is unclear. Because azacitidine clinical data mainly describe experience in higher-risk MDS, we performed a meta-analysis of patient-level data to evaluate azacitidine in patients with red blood cell (RBC) transfusion-dependent LR-MDS...
November 8, 2017: Oncologist
https://www.readbyqxmd.com/read/29110190/pomalidomide-a-review-in-relapsed-and-refractory-multiple-myeloma
#12
Sheridan M Hoy
Pomalidomide (Imnovid(®); Pomalyst(®)), an analogue of thalidomide, is an immunomodulatory agent, with several mechanisms of action (both direct and indirect) thought to be involved in its anti-myeloma activity. Oral pomalidomide is available in several countries for use in combination with low-dose dexamethasone in adults with relapsed and refractory multiple myeloma. In multinational, phase II or III studies in patients with refractory, or relapsed and refractory multiple myeloma who had received ≥ 2 prior treatment regimens (including ≥ 2 cycles of both lenalidomide and bortezomib), pomalidomide plus low-dose dexamethasone was associated with prolonged progression-free survival (PFS) and overall survival and an improved overall response rate...
November 2017: Drugs
https://www.readbyqxmd.com/read/29105343/racial-disparity-in-utilization-of-therapeutic-modalities-among-multiple-myeloma-patients-a-seer-medicare-analysis
#13
Sikander Ailawadhi, Ryan D Frank, Pooja Advani, Abhisek Swaika, M'hamed Temkit, Richa Menghani, Mayank Sharma, Zahara Meghji, Shumail Paulus, Nandita Khera, Shahrukh K Hashmi, Aneel Paulus, Tanya S Kakar, David O Hodge, Dorin T Colibaseanu, Michael R Vizzini, Vivek Roy, Gerardo Colon-Otero, Asher A Chanan-Khan
Outcomes have improved considerably in multiple myeloma (MM), but disparities among racial-ethnic groups exist. Differences in utilization of novel therapeutics are likely contributing factors. We explored such differences from the SEER-Medicare database. A utilization analysis of lenalidomide, thalidomide, bortezomib, and stem cell transplant (SCT) was performed for patients diagnosed with MM between 2007 and 2009, including use over time, use by race, time-dependent trends for each racial subgroup, and survival analysis...
November 3, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/29098319/-multiple-myeloma-what-has-been-confirmed-in-therapy
#14
REVIEW
M-A Baertsch, H Goldschmidt
Multiple myeloma (MM) is a malignancy of terminally differentiated B cells/plasma cells and is primarily located in the bone marrow. Symptomatic multiple myeloma typically presents with osteolyses, anemia, reduced renal function, and/or hypercalcemia. In the case of such MM-related end organ damage, urgent systemic treatment is indicated. In order to prevent end organ damage, current guidelines now recommend treatment initiation already when certain biomarkers are met. Current first-line treatment is based on proteasome inhibition and immunomodulation...
November 2, 2017: Der Internist
https://www.readbyqxmd.com/read/29097499/randomized-study-of-continuous-high-dose-lenalidomide-sequential-azacitidine-and-lenalidomide-or-azacitidine-in-persons-%C3%A2-65-years-with-newly-diagnosed-acute-myeloid-leukemia
#15
Bruno C Medeiros, Kelly McCaul, Suman Kambhampati, Daniel A Pollyea, Rajat Kumar, Lewis R Silverman, Andrea Kew, Lalit Saini, C L Beach, Ravi Vij, Xiwei Wang, Jim Zhong, Robert Peter Gale
Therapy of acute myeloid leukemia in older persons is associated with poor outcomes because of intolerance to intensive therapy, resistant disease and co-morbidities. This multi-center, randomized, open-label, phase-2 trial compared safety and efficacy of three therapeutic strategies in persons ≥65 years with newly-diagnosed acute myeloid leukemia: (1) continuous high-dose lenalidomide (N=15); (2) sequential azacitidine and lenalidomide (N=39); and (3) azacitidine (N=34) only. The efficacy endpoint was 1-year survival...
November 2, 2017: Haematologica
https://www.readbyqxmd.com/read/29096668/observational-study-of-lenalidomide-in-patients-with-mantle-cell-lymphoma-who-relapsed-progressed-after-or-were-refractory-intolerant-to-ibrutinib-mcl-004
#16
Michael Wang, Stephen J Schuster, Tycel Phillips, Izidore S Lossos, Andre Goy, Simon Rule, Mehdi Hamadani, Nilanjan Ghosh, Craig B Reeder, Evelyn Barnett, Marie-Laure Casadebaig Bravo, Peter Martin
BACKGROUND: The observational MCL-004 study evaluated outcomes in patients with relapsed/refractory mantle cell lymphoma who received lenalidomide-based therapy after ibrutinib failure or intolerance. METHODS: The primary endpoint was investigator-assessed overall response rate based on the 2007 International Working Group criteria. RESULTS: Of 58 enrolled patients (median age, 71 years; range, 50-89), 13 received lenalidomide monotherapy, 11 lenalidomide plus rituximab, and 34 lenalidomide plus other treatment...
November 2, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29091475/a-review-discussing-elotuzumab-and-its-use-in-the-second-line-plus-treatment-of-multiple-myeloma
#17
Massimo Offidani, Laura Corvatta
Monoclonal antibodies (mAb) represent a new frontier to treat newly diagnosed and relapsed-refractory multiple myeloma (MM). Elotuzumab, an mAb targeted SLAM7 in the plasma cells and natural killer cells surface, is the first mAb approved for the treatment of relapsed-refractory MM in combination with lenalidomide and dexamethasone. This approval was the final result of several preclinical and Phase I-II clinical studies leading to ELOQUENT-2 Phase III trial that demonstrated that elotuzumab adds a significant and durable value to standard therapy, paved the way of this new treatment strategy for MM...
November 1, 2017: Future Oncology
https://www.readbyqxmd.com/read/29089806/short-course-lenalidomide-plus-low-dose-dexamethasone-in-the-treatment-of-newly-diagnosed-multiple-myeloma-a-single-centre-pragmatic-study
#18
W M Jose, K Pavithran, T S Ganesan
PURPOSE: We assessed response to treatment, toxicity, time to progression, progression-free survival, and overall survival in patients newly diagnosed with multiple myeloma who were ineligible for or unwilling to undergo transplantation and who were treated with a combination of lenalidomide and low-dose dexamethasone for a fixed 6 cycles in a resource-constrained environment. METHODS: This pragmatic study, conducted in a single tertiary cancer centre in South India, enrolled patients from May 2009 till April 2011...
October 2017: Current Oncology
https://www.readbyqxmd.com/read/29078080/relationship-between-lenalidomide-dose-modification-duration-of-therapy-and-long-term-outcomes-in-patients-with-myelodysplastic-syndromes
#19
Amy E DeZern, Gary Binder, Quanhong Ni, Michael McGuire, B Douglas Smith
Dose reductions or interruptions may be required to manage treatment-associated adverse events among patients with myelodysplastic syndromes (MDS) treated with lenalidomide; such modifications are recommended to sustain therapy and maximize treatment duration. The aim of this retrospective case-control study was to determine the relationship between lenalidomide dose modification (DM), duration of lenalidomide therapy (DOT), and patient outcomes in patients with MDS. Those patients with database follow-up >20months (n=305) were more likely to have received erythropoiesis-stimulating agents (ESAs) (P=0...
October 18, 2017: Leukemia Research
https://www.readbyqxmd.com/read/29076150/a-phase-1-clinical-trial-evaluating-marizomib-pomalidomide-and-low-dose-dexamethasone-in-relapsed-and-refractory-multiple-myeloma-npi-0052-107-final-study-results
#20
Andrew Spencer, Simon Harrison, Jeffrey Zonder, Ashraf Badros, Jacob Laubach, Krystal Bergin, Amit Khot, Todd Zimmerman, Dharminder Chauhan, Nancy Levin, Ann MacLaren, Steven D Reich, Mohit Trikha, Paul Richardson
Marizomib (MRZ) is an irreversible, pan-subunit proteasome inhibitor (PI) in clinical development for relapsed/refractory multiple myeloma (RRMM) and glioma. This study analysed MRZ, pomalidomide (POM) and low-dose dexamethasone (Lo-DEX) [PMD] in RRMM to evaluate safety and determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D). Intravenous MRZ (0·3-0·5 mg/m(2) ) was administered over 2 h on days 1, 4, 8, 11; POM (3-4 mg) on days 1-21; and Lo-DEX (5 or 10 mg) on days 1, 2, 4, 5, 8, 9, 11, 12, 15, 16, 22 and 23 of every 28-day cycle...
October 26, 2017: British Journal of Haematology
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