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https://www.readbyqxmd.com/read/29768064/a-look-at-treatment-strategies-for-relapsed-multiple-myeloma
#1
Giusy Cetani, Mario Boccadoro, Stefania Oliva
Multiple myeloma treatment considerably improved during the past decade, thanks to novel effective drugs, a better understanding of myeloma biology and clonal heterogeneity, and an improved management of toxicities. The choice of regimen at relapse is usually based on prior response, toxicities, age and comorbidities of relapsed patients. Areas covered: A review was performed of the most recent and effective therapeutic strategies for the relapsed myeloma setting, by documenting the latest clinical evidence from phase II and III clinical trials...
May 16, 2018: Expert Review of Anticancer Therapy
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
#2
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/29656050/an-expanded-treatment-protocol-of-panobinostat-plus-bortezomib-and-dexamethasone-in-patients-with-previously-treated-myeloma
#3
Vincent L Hansen, Morton Coleman, Stephanie Elkins, Jeffrey P Letzer, Moshe Yair Levy, Lasika Seneviratne, Jessica Rine, Marina White, Emil T Kuriakose
BACKGROUND: Panobinostat was recently approved by the US Food and Drug Administration and European Commission in combination with bortezomib and dexamethasone for patients with multiple myeloma who have received ≥ 2 regimens, including bortezomib and an immunomodulatory drug. The PANEX (panobinostat expansion) treatment protocol provided access to panobinostat and gathered additional safety data before commercial availability. PATIENTS AND METHODS: In treatment phase 1, patients received panobinostat 20 mg 3 times per week plus bortezomib 1...
March 14, 2018: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29615082/response-and-progression-free-survival-according-to-planned-treatment-duration-in-patients-with-relapsed-multiple-myeloma-treated-with-carfilzomib-lenalidomide-and-dexamethasone-krd-versus-lenalidomide-and-dexamethasone-rd-in-the-phase-iii-aspire-study
#4
Meletios Dimopoulos, Michael Wang, Vladimir Maisnar, Jiri Minarik, William Bensinger, Maria-Victoria Mateos, Mihaela Obreja, Julie Blaedel, Philippe Moreau
BACKGROUND: In ASPIRE, carfilzomib, lenalidomide, and dexamethasone (KRd) significantly improved progression-free survival (PFS) and response rates versus lenalidomide and dexamethasone (Rd) in patients with relapsed multiple myeloma. Per protocol, patients received KRd for a maximum of 18 cycles followed by Rd to progression, so the benefit/risk profile of KRd to progression was not established. METHODS: This post hoc analysis evaluated the efficacy and safety of KRd versus Rd at 18 months from randomization...
April 4, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29576386/multiple-myeloma-clinical-updates-from-the-american-society-of-hematology-annual-meeting-2017
#5
REVIEW
Evangelos Terpos
The novel clinical data for myeloma that were presented in the 2017 Annual Meeting of the American Society of Hematology are summarized here. Studies with curative approach (CESAR) or prolonging progression-free survival (CENTAURUS) for patients with high-risk smoldering multiple myeloma (SMM) are described. Updated data from large phase III studies for patients with newly diagnosed MM (NDMM) who are eligible for autologous stem cell transplantation (ASCT) (EMN02, MRC XI) are described, along with the results of studies using novel anti-myeloma drug combinations for induction, consolidation, and maintenance as first-line therapy...
March 1, 2018: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29557059/novel-treatments-for-multiple-myeloma-what-role-do-they-have-in-older-adults
#6
REVIEW
Hira S Mian, Tanya M Wildes
Multiple myeloma is a malignant plasma cell disease, which typically affects older patients, with a median age at diagnosis of 70 years. The recent introduction of novel drugs and ongoing improvements in supportive care have significantly contributed to overall better management and outcomes for patients with multiple myeloma. Autologous stem-cell transplantation has been a standard part of therapy for myeloma patients for many years, first in younger patients and increasingly in older, and may still be considered in selected older patients with myeloma...
March 19, 2018: Drugs & Aging
https://www.readbyqxmd.com/read/29531651/elotuzumab-for-the-treatment-of-relapsed-or-refractory-multiple-myeloma-with-special-reference-to-its-modes-of-action-and-slamf7-signaling
#7
REVIEW
Masafumi Taniwaki, Mihoko Yoshida, Yosuke Matsumoto, Kazuho Shimura, Junya Kuroda, Hiroto Kaneko
Elotuzumab, targeting signaling lymphocytic activation molecule family 7 (SLAMF7), has been approved in combination with lenalidomide and dexamethasone (ELd) for relapsed/refractory multiple myeloma (MM) based on the findings of the phase III randomized trial ELOQUENT-2 (NCT01239797). Four-year follow-up analyses of ELOQUENT-2 have demonstrated that progression-free survival was 21% in ELd versus 14% in Ld. Elotuzumab binds a unique epitope on the membrane IgC2 domain of SLAMF7, exhibiting a dual mechanism of action: natural killer (NK) cell-mediated antibody-dependent cellular cytotoxicity (ADCC) and enhancement of NK cell activity...
2018: Mediterranean Journal of Hematology and Infectious Diseases
https://www.readbyqxmd.com/read/29520705/targeting-bcl-2-in-hematologic-malignancies
#8
Nadia Khan, Brad Kahl
Resistance to apoptosis is one of the hallmarks of cancer and members of the B-cell lymphoma 2 (BCL-2) family of proteins are central regulators of apoptosis. Many cancers become resistant to chemotherapy and apoptosis by up-regulating BCL-2 and other family members, making these proteins attractive targets for cancer therapy. Venetoclax is an orally administered, small-molecule apoptosis stimulant that targets BCL-2 proteins by acting as a BCL-2 homology domain 3 (BH3) mimetic. The drug is approved in the USA and EU as a monotherapy for the for the treatment of certain patients with chronic lymphocytic leukemia (CLL) and is in phase III clinical development for multiple myeloma (MM), and in phase II or I/II clinical trials for acute myeloid leukemia, and several B-cell malignancies, including diffuse large B-cell lymphoma, Waldenstrom's macroglobulinaemia, follicular lymphoma, and mantle-cell lymphoma...
March 8, 2018: Targeted Oncology
https://www.readbyqxmd.com/read/29514706/the-role-of-ixazomib-as-an-augmented-conditioning-therapy-in-salvage-autologous-stem-cell-transplant-asct-and-as-a-post-asct-consolidation-and-maintenance-strategy-in-patients-with-relapsed-multiple-myeloma-accord-uk-mra-myeloma-xii-trial-study-protocol-for
#9
Alina Striha, A John Ashcroft, Anna Hockaday, David A Cairns, Karen Boardman, Gwen Jacques, Cathy Williams, John A Snowden, Mamta Garg, Jamie Cavenagh, Kwee Yong, Mark T Drayson, Roger Owen, Mark Cook, Gordon Cook
BACKGROUND: Multiple myeloma (MM) is a plasma cell tumour with an approximate annual incidence of 4500 in the UK. Therapeutic options for patients with MM have changed in the last decade with the arrival of proteasome inhibitors and immunomodulatory drugs. Despite these options, almost all patients will relapse post first-line autologous stem cell transplantation (ASCT). First relapse management (second-line treatment) has evolved in recent years with an expanding portfolio of novel agents, driving response rates influencing the durability of response...
March 7, 2018: Trials
https://www.readbyqxmd.com/read/29465266/cardiotoxicity-associated-with-carfilzomib-systematic-review-and-meta-analysis
#10
Chintan Shah, Rohit Bishnoi, Ankur Jain, Harini Bejjanki, Sican Xiong, Yu Wang, Fei Zou, Jan S Moreb
Carfilzomib is a second-generation proteasome inhibitor (PI) that is approved for patients with relapsed or refractory multiple myeloma (RRMM) who failed ≥1 prior lines of therapy. We performed a systematic review of carfilzomib literature with meta-analysis to determine cumulative incidence of cardiotoxicity. After the literature search, we included a total of 29 eligible phase I/II, phase II and phase III clinical trials which used carfilzomib. The cumulative incidence and overall odds ratios (OR) were calculated with random effect model, using 'R' software with metaphor package...
February 21, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29410180/plerixafor-plus-granulocyte-colony-stimulating-factor-for-patients-with-non-hodgkin-lymphoma-and-multiple-myeloma-long-term-follow-up-report
#11
Ivana N Micallef, Patrick J Stiff, Auayporn P Nademanee, Richard T Maziarz, Mitchell E Horwitz, Edward A Stadtmauer, Jonathan L Kaufman, John M McCarty, Rita Vargo, Peter D Cheverton, Martin Struijs, Brian Bolwell, John F DiPersio
The purpose of this report is to analyze long-term clinical outcomes of patients exposed to plerixafor plus granulocyte colony-stimulating factor (G-CSF) for stem cell mobilization. This was a study of patients with non-Hodgkin lymphoma (NHL; n = 167) and multiple myeloma (MM; n = 163) who were enrolled in the long-term follow-up of 2 pivotal phase III studies (NCT00741325 and NCT00741780) of 240 µg/kg plerixafor plus 10 µg/kg G-CSF, or placebo plus 10 µg/kg G-CSF to mobilize and collect CD34+ cells for autologous hematopoietic stem cell transplantation...
February 2, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29397842/-expression-level-and-clinical-significance-of-vegf-il-17-%C3%AE-2-mg-and-il-35-in-patients-with-multiple-myeloma
#12
Xiao-Na Jin, Bao-Zhen Zhou, Dang-Feng Zhang
OBJECTIVE: To explore the expression and clinical significance of VEGF, IL-17, β2-MG and IL-35 in patients with multiple myeloma. METHODS: A total of 83 patients with multiple myeloma (MM) from January 2012 to December 2016 were enrolled in MM group, 36 healthy subjects were enrolled in control group. The levels of IL-17, IL-35 and VEGF in serum were detected by ELISA. The levels of β2-MG in serum were measured by radioimmunoassay. The differences of different indexes between 2 groups were compared...
February 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/29371479/ema-review-of-daratumumab-for-the-treatment-of-adult-patients-with-multiple-myeloma
#13
Kyriaki Tzogani, Elisabeth Penninga, Marie Louise Schougaard Christiansen, Doris Hovgaard, Sinan B Sarac, Jorge Camarero Jimenez, Isabel Garcia, Marta Lafuente, Arantxa Sancho-López, Tomas Salmonson, Christian Gisselbrecht, Francesco Pignatti
On May 20, 2016, a conditional marketing authorization valid through the European Union (EU) was issued for daratumumab as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, whose prior therapy included a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD) and who had demonstrated disease progression on the last therapy. The review of daratumumab was conducted under the EMA's accelerated assessment program for drugs that are of major interest for public health, especially from the point of view of therapeutic innovation...
January 25, 2018: Oncologist
https://www.readbyqxmd.com/read/29317395/the-role-of-elotuzumab-in-the-treatment-of-relapsed-or-refractory-multiple-myeloma
#14
REVIEW
Jill M Comeau, Katherine Kelly, Gary W Jean
PURPOSE: The pharmacology, pharmacokinetics, clinical efficacy and safety, cost, and place in therapy of elotuzumab for treatment of relapsed or refractory multiple myeloma (MM) are reviewed. SUMMARY: Elotuzumab is a humanized monoclonal antibody that targets the signaling lymphocytic activation molecule (SLAM) protein SLAMF7 and facilitates an antibody-dependent cellular cytotoxicity interaction between myeloma cells and natural killer cells. Elotuzumab has U.S...
January 15, 2018: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/29192015/the-european-medicines-agency-review-of-panobinostat-farydak-for-the-treatment-of-adult-patients-with-relapsed-and-or-refractory-multiple-myeloma
#15
REVIEW
Kyriaki Tzogani, Paula van Hennik, Ita Walsh, Pieter De Graeff, Annika Folin, Jan Sjöberg, Tomas Salmonson, Jonas Bergh, Edward Laane, Heinz Ludwig, Christian Gisselbrecht, Francesco Pignatti
On August 28, 2015, a marketing authorization valid through the European Union was issued for panobinostat, in combination with bortezomib and dexamethasone, for the treatment of adult patients with relapsed and/or refractory multiple myeloma who have received at least two prior regimens including bortezomib and an immunomodulatory agent (IMiD).Panobinostat is an orally available histone deacetylase (HDAC) inhibitor that inhibits the enzymatic activity of HDAC proteins at nanomolar concentrations. HDAC proteins catalyze the removal of acetyl groups from the lysine residues of histones and some nonhistone proteins...
November 30, 2017: Oncologist
https://www.readbyqxmd.com/read/29168990/model-based-meta-analysis-for-multiple-myeloma-a-quantitative-drug-independent-framework-for-efficient-decisions-in-oncology-drug-development
#16
Zhaoyang Teng, Neeraj Gupta, Zhaowei Hua, Guohui Liu, Vivek Samnotra, Karthik Venkatakrishnan, Richard Labotka
The failure rate for phase III trials in oncology is high; quantitative predictive approaches are needed. We developed a model-based meta-analysis (MBMA) framework to predict progression-free survival (PFS) from overall response rates (ORR) in relapsed/refractory multiple myeloma (RRMM), using data from seven phase III trials. A Bayesian analysis was used to predict the probability of technical success (PTS) for achieving desired phase III PFS targets based on phase II ORR data. The model demonstrated a strongly correlated (R(2) = 0...
November 23, 2017: Clinical and Translational Science
https://www.readbyqxmd.com/read/29134824/an-overview-of-the-role-of-carfilzomib-in-the-treatment-of-multiple-myeloma
#17
REVIEW
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...
December 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/29127588/daratumumab-a-review-in-relapsed-and-or-refractory-multiple-myeloma
#18
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...
December 2017: Drugs
https://www.readbyqxmd.com/read/29110190/pomalidomide-a-review-in-relapsed-and-refractory-multiple-myeloma
#19
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/29091475/a-review-discussing-elotuzumab-and-its-use-in-the-second-line-plus-treatment-of-multiple-myeloma
#20
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...
February 2018: Future Oncology
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