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https://www.readbyqxmd.com/read/28211889/clinical-utility-of-the-revised-international-staging-system-in-unselected-patients-with-newly-diagnosed-and-relapsed-multiple-myeloma
#1
N Tandon, S V Rajkumar, B LaPlant, A Pettinger, M Q Lacy, A Dispenzieri, F K Buadi, M A Gertz, S R Hayman, N Leung, R S Go, D Dingli, P Kapoor, Y Lin, Y L Hwa, A L Fonder, M A Hobbs, S R Zeldenrust, J A Lust, W I Gonsalves, S J Russell, S K Kumar
We analyzed the utility of Revised International staging system (RISS) in an unselected cohort of newly diagnosed multiple myeloma (NDMM; cohort 1), and relapsed/refractory multiple myeloma (RRMM; cohort 2) patients. Cohort 1 included 1900 patients seen within 90 days of diagnosis, from 2005 to 2015, while cohort 2 had 887 patients enrolled in 23 clinical trials at Mayo Clinic. The overall survival (OS) and progression-free survival (PFS) was calculated from the time since diagnosis or trial registration. The median estimated follow up was 5 and 2...
February 17, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28211560/carfilzomib-lenalidomide-and-dexamethasone-in-patients-with-relapsed-multiple-myeloma-categorised-by-age-secondary-analysis-from-the-phase-3-aspire-study
#2
Meletios A Dimopoulos, A Keith Stewart, Tamás Masszi, Ivan Špička, Albert Oriol, Roman Hájek, Laura Rosiñol, David Siegel, Georgi G Mihaylov, Vesselina Goranova-Marinova, Péter Rajnics, Aleksandr Suvorov, Ruben Niesvizky, Andrzej Jakubowiak, Jesus San-Miguel, Heinz Ludwig, Antonio Palumbo, Mihaela Obreja, Sanjay Aggarwal, Philippe Moreau
: A primary analysis of the ASPIRE study found that the addition of carfilzomib to lenalidomide and dexamethasone (carfilzomib group) significantly improved progression-free survival (PFS) compared with lenalidomide and dexamethasone alone (control group) in patients with relapsed multiple myeloma (RMM). This post hoc analysis examined outcomes from ASPIRE in patients categorised by age. In the carfilzomib group, 103/396 patients were ≥70 years old, and in the control group, 115/396 patients were ≥70 years old...
February 17, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28210004/monoclonal-antibody-therapy-in-multiple-myeloma
#3
REVIEW
Cyrille Touzeau, Philippe Moreau, Charles Dumontet
The therapeutic landscape of multiple myeloma (MM) has evolved spectacularly over the past decade with the discovery and validation of proteasome inhibitors and immunomodulatory agents as highly active agents, both in front-line therapy as well as in the relapse and maintenance settings. While previous attempts to apply available monoclonal antibodies (Mabs) to the treatment of patients with MM has until recently been disappointing, novel targets specifically explored in the context of MM have recently lead to the first approvals of Mabs for the treatment of patients with MM...
February 17, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28208219/impact-of-induction-treatment-before-autologous-stem-cell-transplantation-on-long-term-outcome-in-patients-with-newly-diagnosed-multiple-myeloma
#4
Susanna Gassiot, Cristina Motlló, Inuska Llombart, Mireia Morgades, Yolanda González, Montse Garcia-Caro, Josep-Maria Ribera, Albert Oriol
OBJECTIVE: Clinical trials for multiple myeloma patients using novel agent-based regimens before autologous stem cell transplantation (SCT) have shown improvement in response rates and progression-free survival (PFS), however they have failed to identify a significant overall survival (OS) benefit. The aim of this study was to analyze the potential impact of initial induction on the feasibility and outcome of subsequent treatment lines in a real clinical practice setting. METHODS: Consecutive multiple myeloma patients less than 70 years of age diagnosed between 1999 and 2009 were prospectively registered and classified as having received conventional chemotherapy induction regimens with new agents available at relapse (CC cohort, 89 patients) or as treated with novel agents upfront (NA cohort, 65 patients)...
February 16, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28208215/nanoparticle-delivery-systems-general-approaches-and-their-implementation-in-multiple-myeloma
#5
REVIEW
Pilar de la Puente, Abdel Kareem Azab
Multiple myeloma (MM) is a hematological malignancy that remains incurable, with relapse rates greater than 90%. The main limiting factor for the effective use of chemotherapies in MM is the serious side effects caused by these drugs. The emphasis in cancer treatment has shifted from cytotoxic, non-specific chemotherapies to molecularly targeted and rationally designed therapies showing greater efficacy and fewer side effects. Traditional chemotherapy has shown several disadvantages such as lack of targeting capabilities, systemic toxicity and side effects; low therapeutic index, as well as, most anticancer drugs have poor water solubility...
February 16, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28205024/immunomodulatory-drugs-in-multiple-myeloma-mechanisms-of-action-and-clinical-experience
#6
REVIEW
Sarah A Holstein, Philip L McCarthy
Over the last two decades, the outcomes for patients with multiple myeloma, a plasma cell malignancy, have dramatically improved. The development of the immunomodulatory drugs (IMiDs), which include thalidomide, lenalidomide, and pomalidomide, has contributed significantly to these improved outcomes. While thalidomide is now less commonly prescribed, lenalidomide is widely used in the treatment of newly diagnosed transplant-eligible and transplant-ineligible patients, in the maintenance setting post-transplant and in the relapsed/refractory setting, while pomalidomide is currently utilized in the relapsed/refractory setting...
February 16, 2017: Drugs
https://www.readbyqxmd.com/read/28203342/optimizing-current-and-emerging-therapies-in-multiple-myeloma-a-guide-for-the-hematologist
#7
REVIEW
Shahzad Raza, Rachael A Safyan, Evan Rosenbaum, Alex S Bowman, Suzanne Lentzsch
Multiple myeloma (MM) is the second most common hematologic malignancy. The diagnosis of MM requires ⩾10% clonal plasma cells in the bone marrow or biopsy-proven plasmacytoma, plus evidence of end-organ damage (hypercalcemia, renal failure, anemia, and lytic bone lesions). The definition of MM has recently been expanded to include a ⩾60% clonal plasma cell burden in the bone marrow, serum involved/uninvolved light chain ratio of ⩾100, or more than one focal lesion on magnetic resonance imaging ⩾5 mm in the absence of end-organ damage...
February 2017: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/28203341/new-monoclonal-antibodies-on-the-horizon-in-multiple-myeloma
#8
REVIEW
Elizabeth K O'Donnell, Noopur S Raje
Across all cancers, monoclonal antibodies have emerged as a potential strategy for cancer therapy. Monoclonal antibodies target antigens expressed on the surface of cancer cells and accessory cells. This targeted approach uses the host's immune system to promote the killing of cancer cells. Multiple myeloma (MM) is the second most common hematologic malignancy that remains incurable in the majority of patients. The treatment of MM has evolved dramatically over the past decade and continues to evolve with the approval of four new drugs in 2015...
February 2017: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/28203307/epigenetic-strategies-to-reverse-drug-resistance-in-heterogeneous-multiple-myeloma
#9
REVIEW
Mark E Issa, Farnaz Sedigheh Takhsha, Chandra Sekhar Chirumamilla, Claudina Perez-Novo, Wim Vanden Berghe, Muriel Cuendet
Multiple myeloma (MM) is a hematological malignancy, which remains incurable because most patients eventually relapse or become refractory to current treatments. Due to heterogeneity within the cancer cell microenvironment, cancer cell populations employ a dynamic survival strategy to chemotherapeutic treatments, which frequently results in a rapid acquisition of therapy resistance. Besides resistance-conferring genetic alterations within a tumor cell population selected during drug treatment, recent findings also reveal non-mutational mechanisms of drug resistance, involving a small population of "cancer stem cells" (CSCs) which are intrinsically more refractory to the effects of a variety of anticancer drugs...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28201976/immunomodulatory-drugs-imids-in-multiple-myeloma
#10
Shahzad Raza, Rachael A Safyan, Lentzsch Suzanne
Multiple myeloma (MM) is a plasma cell neoplasm that is incurable with conventional therapy. However, the treatment of MM has dramatically changed since the emergence of immunomodulatory drugs and proteasome inhibitors. The improvements in survival are linked to a deeper understanding of the molecular mechanisms of the disease. Thalidomide, although highly active in MM, is associated with considerable toxicity, particularly in older patients. Immunomodulatory drugs (IMiDs) are structural and functional analogues of thalidomide that represent a promising new class of immunomodulators for treatment of a variety of inflammatory, autoimmune, and neoplastic diseases...
February 13, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28197996/upfront-lower-dose-lenalidomide-is-less-toxic-and-does-not-compromise-efficacy-for-vulnerable-patients-with-relapsed-refractory-multiple-myeloma-final-analysis-of-the-phase-ii-revlite-study
#11
Hang Quach, Liam Fernyhough, Ross Henderson, Gillian Corbett, Bart Baker, Peter Browett, Hilary Blacklock, Cecily Forsyth, Craig Underhill, Paul Cannell, Judith Trotman, Annette Neylon, Simon Harrison, Emma Link, Arlene Swern, Linda Cowan, Meletios A Dimopoulos, H Miles Prince
The combination of lenalidomide and dexamethasone is an established treatment for patients with multiple myeloma (MM). Increasingly, treatment attenuation is advocated for frail/elderly patients to minimize toxicity even though there have been no prospective studies to demonstrate whether lenalidomide dose attenuation impacts on response and survival outcome. This prospective multicentre phase II study assessed the efficacy and tolerability of lower dose lenalidomide (15 mg) and dexamethasone (20 mg) in 149 eligible patients with relapsed/refractory MM aged over 59 years and/or with renal impairment...
February 15, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28190864/successful-management-of-venous-thromboembolism-with-apixaban-in-a-multiple-myeloma-patient-on-lenalidomide-therapy
#12
Satoko Oka, Suguru Takeuchi, Hiroshi Shiragami, Keigo Hamahata, Masaharu Nohgawa
A 69-year-old man was diagnosed with multiple myeloma (IgG-κ) in January 2012. He received autologous hematopoietic stem cell transplantation in August 2012 and subsequently maintained a stringent complete remission. In March 2016, he relapsed and was treated with lenalidomide and low-dose dexamethasone (Ld). On day22, he developed an asymptomatic venous thromboembolism (VTE) despite receiving prophylactic aspirin treatment. Thus, heparin and warfarin were administered. However, his prothrombin time-international normalized ratio did not remain within the target range of 2-3...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28181910/clinical-usefulness-of-serum-free-light-chains-measurement-in-patients-with-multiple-myeloma-comparative-analysis-of-two-different-tests
#13
Tadeusz Kubicki, Dominik Dytfeld, Aleksandra Baszczuk, Ewa Wysocka, Mieczysław Komarnicki, Krzysztof Lewandowski
INTRODUCTION: There are two commercially available tests for measurement of serum free light chains (sFLC) in multiple myeloma (MM) patients - Freelite and N Latex FLC. The aim of this study was to perform an assessment and direct comparison of the usefulness of the methods in routine clinical practice. METHODS: 40 refractory/relapsed MM patients underwent routine disease activity assessment studies, along with sFLC analysis using both assays. Correlation and concordance between the tests and sensitivity of studied methods of sFLC assessment were established...
January 4, 2017: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/28176904/plitidepsin-design-development-and-potential-place-in-therapy
#14
REVIEW
Sara Alonso-Álvarez, Emilia Pardal, Diego Sánchez-Nieto, Miguel Navarro, Maria Dolores Caballero, Maria Victoria Mateos, Alejandro Martín
Plitidepsin is a cyclic depsipeptide that was first isolated from a Mediterranean marine tunicate (Aplidium albicans) and, at present, is manufactured by total synthesis and commercialized as Aplidin(®). Its antitumor activity, observed in preclinical in vitro and in vivo studies has prompted numerous clinical trials to be conducted over the last 17 years, alone or in combination with other anticancer agents. Single-agent plitidepsin has shown limited antitumor activity and a tolerable safety profile in several malignancies, such as noncutaneous peripheral T-cell lymphoma, melanoma, and multiple myeloma...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28157697/trip13-impairs-mitotic-checkpoint-surveillance-and-is-associated-with-poor-prognosis-in-multiple-myeloma
#15
Yi Tao, Guang Yang, Hongxing Yang, Dongliang Song, Liangning Hu, Bingqian Xie, Houcai Wang, Lu Gao, Minjie Gao, Hongwei Xu, Zhijian Xu, Xiaosong Wu, Yiwen Zhang, Weiliang Zhu, Fenghuang Zhan, Jumei Shi
AAA-ATPase TRIP13 is one of the chromosome instability gene recently established in multiple myeloma (MM), the second most common and incurable hematological malignancy. However, the specific function of TRIP13 in MM is largely unknown. Using sequential gene expression profiling, we demonstrated that high TRIP13 expression levels were positively correlated with progression, disease relapse, and poor prognosis in MM patients. Overexpressing human TRIP13 in myeloma cells prompted cell growth and drug resistance, and overexpressing murine TRIP13, which shares 93% sequence identity with human TRIP13, led to colony formation of NIH/3T3 fibroblasts in vitro and tumor formation in vivo...
February 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28153487/myeloma-in-the-real-world-what-is-really-happening
#16
REVIEW
Krystal Bergin, Zoe McQuilten, Elizabeth Moore, Erica Wood, Andrew Spencer
Multiple myeloma (MM) is the second most common hematologic malignancy and is predominantly a disease of the elderly. In the past 2 decades, a range of new therapeutic options have become available, leading to improvements in patient outcomes, including both attainment of remission and overall survival. These improved outcomes have heralded a paradigm shift from a palliative approach toward more active management, including the use of sequential therapies, with the goal of prolonging progression-free and overall survival and preserving organ function to enable delivery of further therapy at relapse...
December 26, 2016: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28151712/integration-of-novel-agents-into-the-care-of-patients-with-multiple-myeloma
#17
EDITORIAL
Robert Z Orlowski, Sagar Lonial
The pace of therapeutic drug development in multiple myeloma has reached unprecedented levels, with five regulatory approvals for relapsed and/or refractory disease of either new drugs or new drug regimens in 2015, one already in 2016, and still others anticipated. This has provided a wide array of options to be considered by patients and their health care providers in the event of relapse after or progression on front-line therapy. Most of these agents are currently being evaluated in earlier patient populations, including as parts of induction, consolidation, and maintenance therapy approaches, where their benefits may be even greater...
November 15, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28151709/progress-and-paradigms-in-multiple-myeloma
#18
EDITORIAL
Kenneth C Anderson
Remarkable progress has been achieved in multiple myeloma, and patient median survival has been extended 3- to 4-fold. Specifically, there have been 18 newly approved treatments for multiple myeloma in the past 12 years, including seven in 2015, and the treatment paradigm and patient outcome have been transformed. The definition of patients benefitting from these therapies has been broadened. Response criteria now include minimal residual disease (MRD), assessed in bone marrow by multicolor flow cytometry or sequencing, and by imaging for extramedullary disease...
November 15, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28150872/polymorphism-in-anril-is-associated-with-relapse-in-patients-with-multiple-myeloma-after-autologous-stem-cell-transplant
#19
Ming J Poi, Junan Li, Douglas W Sborov, Zachary VanGundy, Yu Kyoung Cho, Misty Lamprecht, Flavia Pichiorri, Mitch A Phelps, Craig C Hofmeister
Multiple myeloma (MM) is a hematologic malignancy characterized by clonal proliferation of plasma cells and overproduction of monoclonal immunoglobins. Treatment with melphalan is currently standard of care for younger and fit patients when followed by hematopoietic stem cell transplantation (HSCT), and in transplant ineligible patients when used in combination regimens. It has been previously shown that changes in the p53 pathway are associated with melphalan efficacy, but the regulatory role of the p14ARF-MDM2-p53 axis has yet to be fully explored...
February 2, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28144893/a-view-from-the-plateau-is-there-a-role-for-allogeneic-stem-cell-transplantation-in-the-era-of-highly-effective-therapies-for-multiple-myeloma
#20
REVIEW
Damian J Green, William I Bensinger
Allogeneic hematopoietic cell transplant (allo-HCT) represents the earliest form of immunotherapy used to treat multiple myeloma (MM). Since the first successful myeloablative allografts were performed in the early 1980s, highly effective new agents to treat this disease have been identified at an unprecedented pace. Currently, sixteen FDA-approved therapies are available to treat MM. As a consequence of these advances, the median overall survival for standard risk MM patients has extended to over 7 years...
January 31, 2017: Current Hematologic Malignancy Reports
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