scholarly journals DARATUMUMAB FOR THE TREATMENT OF MULTIPLE MYELOMA

2017 ◽  
pp. 94-102
Author(s):  
V. V. Ryzhko ◽  
M. L. Kanaeva
Keyword(s):  
Multiple Myeloma ◽  
Clinical Practice ◽  
Human Monoclonal Antibody ◽  
Proteasome Inhibitors ◽  
Published Data ◽  
Immunomodulatory Drugs ◽  
Combination Therapies ◽  
The Past ◽  
Excellent Safety Profile ◽  
Improvement In Survival

The use of proteasome inhibitors and immunomodulatory drugs in the clinical practice has contributed to the significant improvement in survival for patients with multiple myeloma over the past decades. Alongside this, due to the recurrent course of the disease, there is a need to introduce new classes of drugs to clinical practice. In 2015,  the FDA (USA) approved two monoclonal  antibodies  for use  in  patients  with  relapsed  multiple  myeloma,  and  immunotherapy has  rapidly become indispensable  in the management of such patients. The article presents an analysis of the published data regarding the mechanism of action, safety and clinical efficacy of daratumumab, a human monoclonal antibody that targets CD38 tumor protein, for the  treatment  of patients  with multiple  myeloma. In Russia, daratumumab is registered  (RU LP-004367  of 07.07.2017) and is indicated as monotherapy for patients with relapsed or refractory multiple myeloma, who have received prior therapies, incuding proteasome  inhibitors and immunomodulatory drugs. Daratumumab demonstrated  an excellent safety profile. In the context of daratumumab therapy, the moderate-grade infusion-related reactions occurring mostly during the  first infusion  are the  main adverse  events.  Daratumumab-based combination  therapies  are currently under active evaluation in patients with relapsed and newly diagnosed myeloma.

scholarly journals Refractory IgD Multiple Myeloma Treated with Daratumumab: A Case Report and Literature Review

2016 ◽  
Vol 2016 ◽  
pp. 1-4 ◽  
Author(s):  
Muhammad Husnain ◽  
Sandra Kurtin ◽  
Nikki Barkett ◽  
Irbaz Bin Riaz ◽  
Amit Agarwal
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Median Overall Survival ◽  
Overall Response Rate ◽  
Response Rate ◽  
Human Monoclonal Antibody ◽  
Proteasome Inhibitors ◽  
Recent Analysis ◽  
Immunomodulatory Drugs ◽  
Refractory Multiple Myeloma

Patients with relapsed and refractory multiple myeloma have poor prognosis. A recent analysis of patients with relapsed and refractory multiple myeloma who were refractory to both proteasome inhibitors and immunomodulatory drugs showed the median overall survival of 9 months only. Daratumumab is the first-in-class human monoclonal antibody against CD38 cells which was studied in phase I/II trials for treatment of these patients with relapsed refractory multiple myeloma. It showed an overall response rate of 36% and a median overall survival (OS) of 17 months in these patients. We report a case of 40-year-old man with immunoglobulin D (IgD) multiple myeloma whose disease was refractory to at least 5 different chemotherapy regimens including proteasome inhibitors and immunomodulatory drugs. The clinical studies assessing daratumumab did not include any patients with IgD myeloma which is a rare form of multiple myeloma and to our knowledge is the first study reporting use of daratumumab in IgD myeloma.

scholarly journals Salvage Therapy of Multiple Myeloma: The New Generation Drugs

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Alessandra Romano ◽  
Concetta Conticello ◽  
Maide Cavalli ◽  
Calogero Vetro ◽  
Cosimo Di Raimondo ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Salvage Therapy ◽  
Proteasome Inhibitors ◽  
New Drugs ◽  
Immunomodulatory Drugs ◽  
The Past ◽  
Results Of Treatment ◽  
Incurable Disease ◽  
New Generation ◽  
Historical Treatment

During the past decade, overall results of treatment of multiple myeloma (MM) have been improved and survival curves are now significantly better with respect to those obtained with historical treatment. These improvements are linked to a deeper knowledge of the biology of disease and to the introduction in clinical practice of drugs with different mechanism of action such as proteasome inhibitors and immunomodulatory drugs (IMiDs). However, MM remains in most cases an incurable disease. For patients who relapse after treatment with novel agents, the prognosis is dismal and new drugs and therapeutic strategies are required for continued disease control. In this review, we summarize new insights in salvage therapy for relapsed/refractory MM as emerging from recent clinical trials exploring the activity of bendamustine, new generation proteasome inhibitors, novel IMiDs, monoclonal antibodies, and drugs interfering with growth pathways.

scholarly journals Daratumumab in untreated newly diagnosed multiple myeloma

2019 ◽  
Vol 10 ◽  
pp. 204062071989487 ◽  
Author(s):  
Nadine Abdallah ◽  
Shaji K. Kumar
Keyword(s):  
Multiple Myeloma ◽  
Monoclonal Antibody ◽  
Clinical Trials ◽  
High Risk ◽  
Human Monoclonal Antibody ◽  
Proteasome Inhibitors ◽  
Immunomodulatory Drugs ◽  
Newly Diagnosed ◽  
Infusion Reactions

The treatment of multiple myeloma has evolved markedly in the last decade, but mortality remains high, emphasizing the need for more effective therapies. Daratumumab, a fully human monoclonal antibody targeting CD38, has shown clinical efficacy in relapsed/refractory multiple myeloma both as monotherapy and in combination with other drugs, including novel agents. More recently, promising results have been reported in patients with untreated newly diagnosed multiple myeloma (NDMM). Clinical trials thus far have shown enhanced efficacy and tolerability of several daratumumab-based combinations in both transplant ineligible and eligible patients, without compromising transplant ability. However, benefit in high-risk subpopulations is still unclear. A subcutaneous formulation of daratumumab has been introduced to decrease the risk of infusion reactions, with preliminary results showing non-inferior efficacy. The antimyeloma activity of daratumumab is achieved through multiple mechanisms including direct, Fc-dependent, and immunomodulatory mechanisms. Enhanced efficacy of daratumumab in combination with immunomodulatory drugs and proteasome inhibitors is supported by preclinical data showing synergism. This review will focus on the role of daratumumab in untreated NDMM patients, highlighting the results of major clinical trials, and listing ongoing trials that are evaluating various daratumumab-based combinations in this setting.

scholarly journals High-risk multiple myeloma: how to treat at diagnosis and relapse?

Hematology ◽  
2021 ◽  
Vol 2021 (1) ◽  
pp. 30-36
Author(s):  
María-Victoria Mateos ◽  
Borja Puertas Martínez ◽  
Verónica González-Calle
Keyword(s):  
Multiple Myeloma ◽  
Clinical Trials ◽  
High Risk ◽  
Poor Prognosis ◽  
Proteasome Inhibitors ◽  
Past Century ◽  
The Past ◽  
Baseline Factors ◽  
Novel Therapeutic Strategies ◽  
Improvement In Survival

Abstract Patients with multiple myeloma have experienced a great improvement in survival over the past century because of the introduction of novel therapeutic strategies. However, a subgroup of patients with poorer outcomes than expected is considered high risk and identified by the presence of patient- and disease-based factors such as frailty, extramedullary disease, cytogenetic abnormalities, or even relapses occurring earlier than expected according to the baseline factors. Although the management of patients with high-risk features is not well established because of the lack of specific trials in this subgroup of patients and because of their underrepresentation in the clinical trials, treatment should be planned on 2 pillars: (1) poor prognosis with the presence of high-risk features can be at least improved or even abrogated by achieving a deep and sustained response over time, and (2) this can most likely be obtained through using the best therapeutic options and in a response-adapted way. Some clinical trials that have been planned or are ongoing include only patients with high-risk features, using the most effective therapies (proteasome inhibitors, immunomodulatory drugs, and anti-CD38 monoclonal antibodies) as well as chimeric antigen receptor T cells and T-cell engagers that will unravel what the best therapeutic approach will be to overcome the poor prognosis of the presence of high-risk features.

scholarly journals Selinexor in relapsed/refractory multiple myeloma

2020 ◽  
Vol 11 ◽  
pp. 204062072093062 ◽  
Author(s):  
Joshua Richter ◽  
Deepu Madduri ◽  
Shambavi Richard ◽  
Ajai Chari
Keyword(s):  
Multiple Myeloma ◽  
Hematologic Malignancy ◽  
Proteasome Inhibitors ◽  
Significant Activity ◽  
Combination Drug ◽  
Drug Dosing ◽  
The Past ◽  
Fda Approval ◽  
Drug Choice ◽  
Combination Regimens

Multiple myeloma (MM) represents an incurable hematologic malignancy. Despite significant advances over the past decade, with the advent of multiple new classes of anti-myeloma agents, including immunomodulatory drugs, proteasome inhibitors and monoclonal antibodies, patients ultimately relapse. Selinexor is a first-in-class exportin-1 inhibitor with activity in these multiply relapsed and refractory patients. Although the current Food and Drug Administration (FDA) approval is for the doublet of Selinexor in combination with dexamethasone, ongoing clinical trials are evaluating a number of combination regimens. These triplet and quadruplet, selinexor-based, regimens are showing significant activity in “triple-class” refractory patients. With appropriate combination drug choice, drug dosing, and supportive measures, patients with previously no viable options for therapy, now have multiple potential regimens to control their disease.

scholarly journals Monoclonal Antibody Therapies in Multiple Myeloma: A Challenge to Develop Novel Targets

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Hiroko Nishida ◽  
Taketo Yamada
Keyword(s):  
Multiple Myeloma ◽  
Treatment Options ◽  
Proteasome Inhibitors ◽  
Novel Agents ◽  
Current Status ◽  
Antibody Drug Conjugate ◽  
The Past ◽  
Deacetylase Inhibitor ◽  
Car T ◽  
Immune Therapies

The treatment options in multiple myeloma (MM) has changed dramatically over the past decade with the development of novel agents such as proteasome inhibitors (PIs); bortezomib and immunomodulatory drugs (IMiDs); thalidomide, and lenalidomide which revealed high efficacy and improvement of overall survival (OS) in MM patients. However, despite these progresses, most patients relapse and become eventually refractory to these therapies. Thus, the development of novel, targeted immunotherapies has been pursued aggressively. Recently, next-generation PIs; carfilzomib and ixazomib, IMiD; pomalidomide, histone deacetylase inhibitor (HDADi); panobinostat and monoclonal antibodies (MoAbs); and elotuzumab and daratumumab have emerged, and especially, combination of mAbs plus novel agents has led to dramatic improvements in the outcome of MM patients. The field of immune therapies has been accelerating in the treatment of hematological malignancies and has also taken center stage in MM. This review focuses on an overview of current status of novel MoAb therapy including bispecific T-cell engager (BiTE) antibody (BsAb), antibody-drug conjugate (ADC), and chimeric antigen receptor (CAR) T cells, in relapsed or refractory MM (RRMM). Lastly, investigational novel MoAb-based therapy to overcome immunotherapy resistance in MM is shown.

scholarly journals New Insights into Therapeutic Targets in Myeloma

Hematology ◽  
2011 ◽  
Vol 2011 (1) ◽  
pp. 184-190 ◽  
Author(s):  
Kenneth C. Anderson
Keyword(s):  
Rapid Evolution ◽  
Proteasome Inhibitors ◽  
Complete Response ◽  
Patient Stratification ◽  
Immunomodulatory Drugs ◽  
Combination Therapies ◽  
Number Of Patients ◽  
Treatment Paradigm ◽  
Novel Targets ◽  
And Personalized Medicine

Abstract Patient outcome in multiple myeloma (MM) has been remarkably improved due to the use of combination therapies including proteasome inhibitors and immunomodulatory drugs, which target the tumor in its BM microenvironment. Ongoing efforts to improve the treatment paradigm even further include using oncogenomics to better characterize molecular pathogenesis and to develop refined patient stratification and personalized medicine in MM; using models of MM in its BM milieu to identify novel targets and to validate next-generation therapeutics directed at these targets; developing immune-based therapies including mAbs, immunotoxins targeting MM cells and cytokines, and novel vaccine strategies; and using functional oncogenomics to inform the design of novel combination therapies. With continued rapid evolution of progress in these areas, MM will be a chronic illness with sustained complete response in a significant number of patients.

Survival gains in multiple myeloma from 2003 to 2014.

2018 ◽  
Vol 36 (30_suppl) ◽  
pp. 98-98
Author(s):  
Rafael Fonseca ◽  
Anupam B. Jena ◽  
Desi Peneva ◽  
Zoe Clancy
Keyword(s):  
Multiple Myeloma ◽  
Survival Data ◽  
Treatment Options ◽  
The United States ◽  
Novel Therapies ◽  
Full Sample ◽  
The Past ◽  
Improvement In Survival ◽  
Second Wave ◽  
Novel Agent

98 Background: Survival probabilities for patients with multiple myeloma have increased considerably over the past several decades, and a conservative estimate of 5-year survival today is approximately 50%, perhaps higher with optimal treatment. Treatment options for multiple myeloma have grown significantly beginning in 2003 with the approval of bortezomib, followed by approvals for lenalidomide and thalidomide in 2006. The second wave of novel agent approvals began in 2012 with carfilzomib, followed by pomalidomide in 2013. The aim of this study was to estimate the survival gains associated with multiple myeloma therapies after the introduction of novel therapies beginning in 2003 in the United States. Methods: We estimated survival gains for multiple myeloma patients diagnosed in the 5-year period from 2010-2014—who had access to newer therapies like lenalidomide, bortezomib, pomalidomide, and carfilzomib—compared with patients diagnosed in the 5 years prior to the approval of bortezomib (1998–2002). We used data from the Surveillance, Epidemiology, and End Results (SEER) Program cancer registry and a generalized gamma regression survival model. The sample from SEER included patients aged > 18 years who had a diagnosis of multiple myeloma between 1983 and 2014. Results: Of 88,462 patients identified in the full sample, 14,446 patients were diagnosed in 1998–2002 and 25,948 patients were diagnosed in 2010–2014. Overall survival was 51% longer ( P< 0.001) in multiple myeloma patients diagnosed in 2010–2014 than in patients diagnosed in 1998–2002. Patients diagnosed in 2010–2014 had median and mean survival of 1.32 and 2.27 years longer, respectively, than patients diagnosed in 1998–2002. Conclusions: Patients diagnosed with multiple myeloma during 2010–2014 had significant improvement in survival relative to patients diagnosed in 1998–2002. This study found continued improvement in survival in multiple myeloma patients in the most recent 5-years of survival data available, demonstrating the considerable progress made since the wave of multiple myeloma innovation began in 2003.

scholarly journals Molecularly Targeted Therapies in Multiple Myeloma

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Pilar de la Puente ◽  
Barbara Muz ◽  
Feda Azab ◽  
Micah Luderer ◽  
Abdel Kareem Azab
Keyword(s):  
Multiple Myeloma ◽  
Monoclonal Antibodies ◽  
Tumor Microenvironment ◽  
Cell Signaling ◽  
Targeted Therapies ◽  
Proteasome Inhibitors ◽  
Novel Agents ◽  
Immunomodulatory Drugs ◽  
Therapeutic Outcomes

Multiple myeloma (MM) is a hematological malignancy that remains incurable because most patients will eventually relapse or become refractory to the treatments. Although the treatments have improved, the major problem in MM is the resistance to therapy. Novel agents are currently in development for the treatment of relapsed/refractory MM, including immunomodulatory drugs, proteasome inhibitors, monoclonal antibodies, cell signaling targeted therapies, and strategies targeting the tumor microenvironment. We have previously reviewed in detail the contemporary immunomodulatory drugs, proteasome inhibitors, and monoclonal antibodies therapies for MM. Therefore, in this review, we focused on the role of molecular targeted therapies in the treatment of relapsed/refractory multiple myeloma, including cell signaling targeted therapies (HDAC, PI3K/AKT/mTOR, p38 MAPK, Hsp90, Wnt, Notch, Hedgehog, and cell cycle) and strategies targeting the tumor microenvironment (hypoxia, angiogenesis, integrins, CD44, CXCR4, and selectins). Although these novel agents have improved the therapeutic outcomes for MM patients, further development of new therapeutic agents is warranted.

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