scholarly journals Monoclonal Antibodies: Leading Actors in the Relapsed/Refractory Multiple Myeloma Treatment

2020 ◽  
Vol 13 (12) ◽  
pp. 426
Author(s):  
Sonia Morè ◽  
Maria Petrucci ◽  
Laura Corvatta ◽  
Francesca Fazio ◽  
Massimo Offidani ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Monoclonal Antibodies ◽  
Preliminary Data ◽  
Clinical Studies ◽  
Hematologic Malignancy ◽  
Therapeutic Options ◽  
Phase Iii ◽  
Incurable Disease ◽  
Phase Iii Trials ◽  
Phase Ii And Iii

Multiple myeloma is a complex hematologic malignancy, and despite a survival improvement related to the growing number of available therapeutic options since 2000s, it remains an incurable disease with most patients experiencing relapse. However, therapeutic options for this disease are constantly evolving and immunotherapy is becoming the mainstay of the therapeutic armamentarium of Multiple Myeloma (MM), starting with monoclonal antibodies (MoAbs) as elotuzumab, daratumumab and isatuximab. Elotuzumab, the first in class targeting SLAMF7, in combination with lenalidomide and dexamethasone and daratumumab, directed against CD38, in combination with Rd and with bortezomib and dexamethasone (Vd), have been approved for the treatment of relapsed/refractory MM (RRMM) after they demonstrated excellent efficacy. More recently, another anti-CD38 MoAb named isatuximab was approved by FDA in combination with pomalidomide-dexamethasone (Pd) in the same setting. Many phase II and III trials with regimens containing these MoAbs are ongoing, and when available, preliminary data are very encouraging. In this review we will describe the results of major clinical studies that have been conducted with elotuzumab, daratumumab and isatuximab in RRMM, focusing on phase III trials. Moreover, we will summarized the emerging MoAbs-based combinations in the RRMM landscape.

Elotuzumab in the treatment of relapsed and refractory multiple myeloma

2021 ◽  
Author(s):  
Sebastian Grosicki ◽  
Martyna Bednarczyk ◽  
Agnieszka Barchnicka ◽  
Olga Grosicka
Keyword(s):  
Multiple Myeloma ◽  
Monoclonal Antibodies ◽  
Natural Killer Cells ◽  
Natural Killer ◽  
Clinical Studies ◽  
Mechanisms Of Action ◽  
Incurable Disease ◽  
The Us ◽  
Us Fda ◽  
Humanized Monoclonal Antibodies

Multiple myeloma (MM) is still considered an incurable disease. However, drugs with different mechanisms of action that can improve the efficiency of treatment offer hope. Still, there are concerns about an unacceptable increase in toxicity with such regimens. The results of recently published clinical studies of elotuzumab in combination with lenalidomide/dexamethasone or pomalidomide/dexamethasone confirm previous hopes to improve the effect of that treatment. Humanized monoclonal antibodies aimed at SLAMF7 stimulate natural killer cells to fight against MM cells. Elotuzumab used in combination with lenalidomide/dexamethasone or with pomalidomide/dexamethasone is approved by the US FDA to treat patients with relapsed and/or refractory MM. The article is a summary of the recent knowledge about the possibility of using elotuzumab in the treatment of relapsed and/or refractory MM and shows its potential uses in the future.

scholarly journals Monoclonal Antibodies for the Treatment of Multiple Myeloma: An Update

2018 ◽  
Vol 19 (12) ◽  
pp. 3924 ◽  
Author(s):  
Hanley Abramson
Keyword(s):  
Multiple Myeloma ◽  
Monoclonal Antibodies ◽  
Checkpoint Inhibitors ◽  
Proteasome Inhibition ◽  
Phase Iii ◽  
Drug Conjugates ◽  
Fda Approval ◽  
Promising Target ◽  
High Death ◽  
Phase Iii Trials

The past two decades have seen a revolution in multiple myeloma (MM) therapy with the introduction of several small molecules, mostly orally effective, whose mechanisms are based on proteasome inhibition, histone deacetylase (HDAC) blockade, and immunomodulation. Immunotherapeutic approaches to MM treatment using monoclonal antibodies (mAbs), while long in development, began to reap success with the identification of CD38 and SLAMF7 as suitable targets for development, culminating in the 2015 Food and Drug Administration (FDA) approval of daratumumab and elotuzumab, respectively. This review highlights additional mAbs now in the developmental pipeline. Isatuximab, another anti-CD38 mAb, currently is under study in four phase III trials and may offer certain advantages over daratumumab. Several antibody-drug conjugates (ADCs) in the early stages of development are described, including JNJ-63723283, which has attained FDA breakthrough status for MM. Other mAbs described in this review include denosumab, recently approved for myeloma-associated bone loss, and checkpoint inhibitors, although the future status of the latter combined with immunomodulators has been clouded by unacceptably high death rates that caused the FDA to issue clinical holds on several of these trials. Also highlighted are the therapies based on the B Cell Maturation Antigen (BCMA), another very promising target for anti-myeloma development.

scholarly journals Monoclonal Antibodies for the Treatment of Multiple Myeloma: An Update

2018 ◽  
Author(s):  
Hanley Abramson
Keyword(s):  
Multiple Myeloma ◽  
Monoclonal Antibodies ◽  
Checkpoint Inhibitors ◽  
Proteasome Inhibition ◽  
Phase Iii ◽  
Drug Conjugates ◽  
Fda Approval ◽  
Promising Target ◽  
High Death ◽  
Phase Iii Trials

The past two decades have seen a revolution in multiple myeloma (MM) therapy with the introduction of several small molecules, mostly orally effective, whose mechanisms are based on proteasome inhibition, histone deacetylase (HDAC) blockade, and immunomodulation. Immunotherapeutic approaches to MM treatment using monoclonal antibodies (mAbs), while long in development, began to reap success with the identification of CD38 and SLAMF7 as suitable targets for development, culminating in the 2015 FDA approval of daratumumab and elotuzumab, respectively. This review highlights additional mAbs now in the developmental pipeline. Isatuximab, another anti-CD38 mAb, currently is under study in four phase III trials and may offer certain advantages over daratumumab. Several antibody-drug conjugates (ADCs) in the early stages of development are described, including JNJ-63723283, which has attained FDA breakthrough status for MM. Other mAbs described in this review include denosumab, recently approved for myeloma-associated bone loss, and checkpoint inhibitors, although the future status of the latter combined with immunomodulators has been clouded by unacceptably high death rates that caused the FDA to issue clinical holds on several of these trials. Also highlighted are therapies based on the B Cell Maturation Antigen (BCMA), another very promising target for anti-myeloma development.

Clinical implications and outcomes of the ORION Phase III trials

2020 ◽  
Author(s):  
Julia Brandts ◽  
Kausik K Ray
Keyword(s):  
Familial Hypercholesterolemia ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Phase Iii ◽  
Atherosclerotic Cardiovascular Disease ◽  
Low Density Lipoprotein Cholesterol ◽  
Clinical Safety ◽  
Phase Iii Trials ◽  
Phase Ii And Iii ◽  
Ongoing Phase

Inclisiran is a siRNA inhibiting hepatic PCSK9 synthesis. As a first-in-class therapy, inclisiran has been assessed within the ORION trial program for its low-density lipoprotein cholesterol (LDL-C) lowering efficacy and clinical safety. Phase II and III trials have shown that inclisiran lowers LDL-C by about 50% with an infrequent dosing schedule in patients with established atherosclerotic cardiovascular disease and those at high risk, including patients with heterozygous familial hypercholesterolemia. Ongoing Phase III trials will provide evidence on longer-term safety and effectiveness, and inclisiran’s efficacy in patients with homozygous familial hypercholesterolemia. Furthermore, the ORION-4 trial will assess inclisiran’s impact on cardiovascular outcomes.

scholarly journals Stem-cell transplantation in multiple myeloma: how far have we come?

2019 ◽  
Vol 10 ◽  
pp. 204062071988811 ◽  
Author(s):  
Cinnie Y. Soekojo ◽  
Shaji K. Kumar
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Residual Disease ◽  
Phase Iii ◽  
Novel Agents ◽  
Optimal Timing ◽  
High Dose ◽  
Phase Iii Trials

High-dose therapy (HDT) and autologous stem-cell transplantation (ASCT) has historically been an essential part of multiple myeloma (MM) management since early studies demonstrated its efficacy in relapsed disease, and subsequent phase III trials demonstrated better responses and improved survival with this modality compared with standard chemotherapy. With further advances in the MM treatment landscape, including the development of potent novel agents, there has been an increasing debate around various aspects of ASCT, including the optimal timing, role of single versus tandem ASCT, and the practice of consolidation and maintenance therapy post-ASCT. Routine incorporation of the novel agents at each of the treatment phases, induction, consolidation when used, and maintenance has led to better responses as reflected by increasing rates of minimal residual disease (MRD) negativity, longer progression-free survival (PFS) with improvement in overall survival (OS) and in some of the trials. The phase III trials over the last decade have provided significant clarity on the current approach, and have raised important questions regarding the applicability of this modality in all patients. This review aims to summarize the latest literature in the field and discusses how these findings impact the practice of ASCT today.

Therapeutic Applications of Monoclonal Antibodies in Multiple Sclerosis

2019 ◽  
Author(s):  
Hadis Musavi ◽  
Hemen Moradi-Sardareh ◽  
Mohammad Javad Mousavi ◽  
Saeed Aslani ◽  
Amirhooman Asadi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Monoclonal Antibody ◽  
Monoclonal Antibodies ◽  
Late Phase ◽  
Antibody Therapy ◽  
Structural Features ◽  
Chronic Inflammatory Disease ◽  
Phase Iii ◽  
Complement Dependent Cytotoxicity ◽  
Phase Iii Trials

Despite the various therapies available, the use of monoclonal antibodies is a highly specific approach that has only recently been of interest to researchers. The properties of antibodies have led to their use in the treatment of various diseases, including cancer, Alzheimer's disease, diabetes and multiple sclerosis (MS). MS, a chronic inflammatory disease, occurs commonly in young adults. The disease is one of the attractive options for monoclonal antibody therapy because it has no definitive drug for its treatment. Antibodies, by targeting different molecules, have different mechanisms to improve the disease. Treatment with monoclonal antibody has culminated in a clear divergence in paradigm and concentration in MS therapeutics. Application of monoclonal antibody in early inflammatory phases can inhibit or postpone the disability in MS subjects. Ocrelizumab and daclizumab are currently under investigation by late phase III trials, and some other monoclonal antibodies are in the early stages of clinical trials. Monoclonal antibodies are of special structural features (including chimeric, humanized, or fully humanized) as well as specific targets (such as stimulation of signal transduction by binding to receptors, blocking interactions, antibody-dependent cell cytotoxicity, complement-dependent cytotoxicity), thus providing various mechanisms of actions during MS therapy. In the present paper, we reviewed different monoclonal antibodies used in MS, their mechanism of action and theirs target molecules.

Capecitabine and irinotecan (XELIRI) in first-line treatment of metastatic colorectal cancer (mCRC): A systematic review of controlled clinical trials

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15100-e15100
Author(s):  
S. Sukumaran ◽  
N. Pavlakis ◽  
K. B. Pittman ◽  
K. Patterson ◽  
T. J. Price
Keyword(s):  
Phase Ii ◽  
Phase Iii ◽  
Line Treatment ◽  
Phase Ii Trials ◽  
First Line ◽  
Hand Foot Syndrome ◽  
Phase Iii Trials ◽  
Grade 3 ◽  
Phase Ii And Iii ◽  
First Line Treatment

e15100 Background: Irinotecan and 5-Fluorouracil based combination is an effective regimen for mCRC. Capecitabine, an oral fluoropyrimidine, is a convenient alternative to intravenous 5- Fluorouracil. This study aims to systematically review all published and unpublished controlled phase II and III trials of XELIRI combination, used in first line treatment of mCRC, reported from 2000–2008, to describe its efficacy and safety. Methods: A literature search of MEDLINE, EMBASE, CINAHL and proceedings from ASCO, ESMO and WGIC was conducted. The primary end point was response rate (RR), secondary endpoints include: time to progression (TTP), overall survival (OS) and toxicity. Results: Thirty non-randomised phase II trials (n = 1380) along with 6 randomised phase II and 3 phase III trials, were included (pooled n = 1478). The daily dose of capecitabine ranged from 1,800 mg/m2 to 2,500 mg/m2 for 7 to 14 days per cycle and the dose of irinotecan varied from 180mg/m2 to 350 mg/m2, over a 3 week period per cycle. Amongst the non-randomised studies, the median patient age was 61 years (53–72).The median RR was 46.75% (25–78%). The median reported TTP was 7.9 months (mo) (5- 9.9 mo) and the median OS was 15.6 months (7–24.8 mo). Grade 3–4 toxicity incidence was: diarrhoea (21.5%), neutropenia (12%), vomiting (12.5%), fatigue (6%) and Hand-foot syndrome (6%). The pooled incidence of febrile neutropenia was 2.5%. Amongst the randomised trials, the comparator regimens were XELOX or FOLFIRI. Median age was 65 years (61–74). RR for XELIRI was 39% (34–56%) compared to 47% (27–61.8%) for the non XELIRI comparator arms. Median reported TTP was 8.2 mo (5.7–12.5 mo) for the XELIRI arms and 9.2 mo for the comparator arms. Conclusions: XELIRI is an effective and feasible regime in the first line management of mCRC. However the optimal role of this combination remains to be established. No significant financial relationships to disclose.

scholarly journals Efficacy of Panobinostat for the Treatment of Multiple Myeloma

2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Evangelos Eleutherakis-Papaiakovou ◽  
Nikolaos Kanellias ◽  
Efstathios Kastritis ◽  
Maria Gavriatopoulou ◽  
Evangelos Terpos ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Practice ◽  
Proteasome Inhibitors ◽  
Phase Iii ◽  
Toxicity Profile ◽  
Therapeutic Landscape ◽  
Heavily Pretreated ◽  
Phase Iii Trials ◽  
Clinical Potential ◽  
Shed Light

Panobinostat represents a potent oral nonselective pan-histone deacetylase inhibitor (HDAC) with activity in myeloma patients. It has been approved by the FDA and EMA in combination with bortezomib and dexamethasone for the treatment of multiple myeloma, in patients who have received at least two prior regimens, including bortezomib and an immunomodulatory agent. In order to further explore its clinical potential, it is evaluated in different combinations in relapsed/refractory and newly diagnosed multiple myeloma. This review focuses on available data about panobinostat’s pharmacology and its role in clinical practice. This review will reveal panobinostat’s efficacy as antimyeloma treatment, describing drug evolution from preclinical experimental administration to administration in phase III trials, which established its role in current clinical practice. Based on the latest data, we will present its mechanism of action, its efficacy, and most important issues regarding its toxicity profile. We will further try to shed light on its role in current and future therapeutic landscape of myeloma patients. Panobinostat retains its role in therapy of multiple myeloma because of its manageable toxicity profile and its efficacy, mainly in heavily pretreated multiple myeloma patients. These characteristics make it valuable also for novel regimens in combination with second-generation proteasome inhibitors, IMiDs, and monoclonal antibodies. Results of ongoing trials are expected to shed light on drug introduction in different therapeutic combinations or even at an earlier level of disease course.

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