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Elotuzumab

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https://www.readbyqxmd.com/read/29456035/a-comparison-of-the-efficacy-of-immunomodulatory-containing-regimens-in-relapsed-refractory-multiple-myeloma-a-network-meta-analysis
#1
Meletios Athanasios Dimopoulos, Jonathan L Kaufman, Darrell White, Gordon Cook, Maria Rizzo, Yingxin Xu, Kyle Fahrbach, Maren Gaudig, Mary Slavcev, Lindsay Dearden, Annette Lam
BACKGROUND: Previous network meta-analyses combined studies of immunomodulatory drug (IMiD)-containing and IMiD-free regimens, despite a lack of head-to-head randomized controlled trials to robustly link them. However, patients with relapsed or refractory multiple myeloma (RRMM) treated with IMiD-containing regimens differ from those treated with IMiD-free regimens, especially relating to treatment history, which is an important treatment-effect modifier requiring clinical consideration when evaluating the most appropriate subsequent treatment options...
January 5, 2018: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29317395/the-role-of-elotuzumab-in-the-treatment-of-relapsed-or-refractory-multiple-myeloma
#2
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/29296719/pd-1-blockade-enhances-elotuzumab-efficacy-in-mouse-tumor-models
#3
Natalie A Bezman, Amy Jhatakia, Alper Y Kearney, Ty Brender, Mark Maurer, Karla Henning, Misty R Jenkins, Amy J Rogers, Paul J Neeson, Alan J Korman, Michael D Robbins, Robert F Graziano
Elotuzumab, a humanized monoclonal antibody that binds human signaling lymphocytic activation molecule F7 (hSLAMF7) on myeloma cells, was developed to treat patients with multiple myeloma (MM). Elotuzumab has a dual mechanism of action that includes the direct activation of natural killer (NK) cells and the induction of NK cell-mediated antibody-dependent cellular cytotoxicity. This study aimed to characterize the effects of elotuzumab on NK cells in vitro and in patients with MM and to determine whether elotuzumab antitumor activity was improved by programmed death receptor-1 (PD-1) blockade...
May 9, 2017: Blood Advances
https://www.readbyqxmd.com/read/29290170/cost-effectiveness-of-drugs-to-treat-relapsed-refractory-multiple-myeloma-in-the-united-states
#4
Josh J Carlson, Gregory F Guzauskas, Richard H Chapman, Patricia G Synnott, Shanshan Liu, Elizabeth T Russo, Steven D Pearson, Elizabeth D Brouwer, Daniel A Ollendorf
BACKGROUND: New 3-drug regimens have been developed and approved to treat multiple myeloma (MM). The absence of direct comparative data and the high cost of treatment support the need to assess the relative clinical and economic outcomes across all approved regimens. OBJECTIVE: To evaluate the cost-effectiveness of treatments for relapsed and/or refractory MM from a U.S. health system perspective. METHODS: We developed a partition survival model with 3 health states (progression-free, progression, and death) to evaluate the following regimens: carfilzomib (CFZ), elotuzumab (ELO), ixazomib (IX), daratumumab (DAR), and panobinostat (PAN) in combination with lenalidomide (LEN) or bortezomib (BOR) plus dexamethasone (DEX) in the second and/or third line of therapy...
January 2018: Journal of Managed Care & Specialty Pharmacy
https://www.readbyqxmd.com/read/29290169/evaluating-oncology-value-based-frameworks-in-the-u-s-marketplace-and-challenges-in-real-world-application-a-multiple-myeloma-test-case
#5
Laurence M Djatche, Joseph A Goble, Grace Chun, Stefan Varga
BACKGROUND: With the continuous rise in costs for oncology drugs, the American Society of Clinical Oncology (ASCO), the Institute for Clinical and Economic Review (ICER), the Memorial Sloan Kettering Cancer Center's Drug Abacus (DrugAbacus), and the National Comprehensive Cancer Network (NCCN) have developed value-based frameworks (VBFs) to assist stakeholders in formulary and treatment decision-making processes. Since emerging VBFs have the potential to affect available treatment options for patients, it is important to understand the differences associated with these VBFs within various therapeutic areas...
January 2018: Journal of Managed Care & Specialty Pharmacy
https://www.readbyqxmd.com/read/29244720/functional-imaging-with-18f-fdg-pet-ct-and-diffusion-weighted-imaging-dwi-in-early-response-evaluation-of-combination-therapy-of-elotuzumab-lenalidomide-and-dexamethasone-in-a-relapsed-multiple-myeloma-patient
#6
Christos Sachpekidis, Antonia Dimitrakopoulou-Strauss, Stefan Delorme, Hartmut Goldschmidt
Elotuzumab is the first monoclonal antibody approved for the treatment of relapsed-refractory multiple myeloma (MM) in combination with lenalidomide, an immunodulatory drug, and dexamethasone. We report on a multiply pre-treated MM patient with disease progression due to appearance of new focal lesions on imaging modalities, who was started on a combination treatment of elotuzumab, lenalidomide, and dexamethasone. After completion of three cycles of the new therapy the patient responded very well with a major decline of serological myeloma activity parameters serum monoclonal protein, kappa light chains, free light chains (FLC) ratio...
December 15, 2017: Diagnostics
https://www.readbyqxmd.com/read/29200420/the-effect-of-novel-therapies-in-high-molecular-risk-multiple-myeloma
#7
Guido Lancman, Douglas Tremblay, Kevin Barley, Bart Barlogie, Hearn Jay Cho, Sundar Jagannath, Deepu Madduri, Erin Moshier, Samir Parekh, Ajai Chari
Multiple myeloma is a heterogeneous disease with a prognosis that varies with patient factors, disease burden, tumor biology, and treatments. Certain molecular abnormalities confer a worse prognosis and thus are considered high-risk. These include t(4;14), del(17p), t(14;16), t(14;20), hypodiploidy, and gain(1q)/del(1p). In our previous review in 2013, we discussed the effect of available therapies on prognosis in these high-risk patients. Since then, seven phase 3 clinical trials in relapsed myeloma with 1 to 3 lines of therapy have been conducted, resulting in the approval of panobinostat, ixazomib, daratumumab, and elotuzumab, as well as additional data on carfilzomib...
November 2017: Clinical Advances in Hematology & Oncology: H&O
https://www.readbyqxmd.com/read/29188449/current-and-new-therapeutic-strategies-for-relapsed-and-refractory-multiple-myeloma-an-update
#8
REVIEW
Inger S Nijhof, Niels W C J van de Donk, Sonja Zweegman, Henk M Lokhorst
Although survival of multiple myeloma patients has at least doubled during recent years, most patients eventually relapse, and treatment at this stage may be particularly complex. At the time of relapse, the use of alternative drugs to those given upfront is current practice. However, many new options are currently available for the treatment of relapsed multiple myeloma, including recently approved drugs, such as the second- and third-generation proteasome inhibitors carfilzomib and ixazomib, the immunomodulatory agent pomalidomide, the monoclonal antibodies daratumumab and elotuzumab and the histone deacetylase inhibitor panobinostat, but also new targeted agents are under active investigation (e...
November 29, 2017: Drugs
https://www.readbyqxmd.com/read/29098319/-multiple-myeloma-what-has-been-confirmed-in-therapy
#9
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/29091475/a-review-discussing-elotuzumab-and-its-use-in-the-second-line-plus-treatment-of-multiple-myeloma
#10
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/29089311/slamf7-car-t-cells-eliminate-myeloma-and-confer-selective-fratricide-of-slamf7-normal-lymphocytes
#11
Tea Gogishvili, Sophia Danhof, Sabrina Prommersberger, Julian Rydzek, Martin Schreder, Christian Brede, Hermann Einsele, Michael Hudecek
SLAMF7 is under intense investigation as a target for immunotherapy in multiple myeloma. Here, we redirected the specificity of T-cells to SLAMF7 through expression of a chimeric antigen receptor (CAR) derived from the huLuc63 antibody (Elotuzumab), and demonstrate that SLAMF7-CAR T-cells prepared from patients and healthy donors confer potent antimyeloma reactivity. We confirmed uniform, high-level expression of SLAMF7 on malignant plasma cells in previously untreated and in relapsed/refractory (R/R) myeloma patients who had received prior treatment with proteasome-inhibitors and immunomodulatory agents (IMiDs)...
October 31, 2017: Blood
https://www.readbyqxmd.com/read/28978849/therapeutic-approach-for-relapsed-refractory-multiple-myeloma-the-logic-and-practice
#12
Junya Kuroda
The long-term outcome of multiple myeloma (MM) has been greatly improved by the advent of new agents such as proteasome inhibitors (PIs) and immunomodulatory drugs (IMiDs), despite the disease remaining mostly incurable. Treatment design is the critical determinant for the survival period and for the quality and way of life in patients with relapsed/refractory MM (RRMM). Recently, the choice of therapeutic options for RRMM has been expanded by the introduction of second generation PIs such as carfilzomib and ixazomib, and therapeutic monoclonal antibodies such as elotuzumab and daratumumab...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28977957/meta-analysis-of-the-efficacy-of-treatments-for-newly-diagnosed-and-relapsed-refractory-multiple-myeloma-with-del-17p
#13
Jinghua Liu, Hui Yang, Xiaochan Liang, Yuxin Wang, Jian Hou, Yanqin Liu, Jigang Wang, Fan Zhou
We analyzed the treatment of newly diagnosed and relapsed/refractory multiple myeloma (NDMM/RRMM) patients with del(17p). Thirteen prospective studies that evaluated 3,187 MM patients, including 685with del(17p), were included in our meta-analysis. The incidence of del(17p) in NDMM and RRMM patients was similar (13% vs. 14%, respectively, P = 0.64, I2 = 94%). The overall response rate (ORR) to new agents was 40.5% and 67.1%, respectively, in RRMM patients with or without del(17p) (P = 0.1, I2 = 63.9%). NDMM patients with del(17p) treated with PAD (bortezomib, adriamycin, and dexamethasone) induction therapy followed by bortezomib maintenance therapy had higher progression-free survival (PFS) (25...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28932638/the-anti-slamf7-antibody-elotuzumab-mediates-nk-cell-activation-through-both-cd16-dependent-and-independent-mechanisms
#14
Tatiana Pazina, Ashley M James, Alexander W MacFarlane, Natalie A Bezman, Karla A Henning, Christine Bee, Robert F Graziano, Michael D Robbins, Adam D Cohen, Kerry S Campbell
Elotuzumab is a humanized therapeutic monoclonal antibody directed to the surface glycoprotein SLAMF7 (CS1, CRACC, CD319), which is highly expressed on multiple myeloma (MM) tumor cells. Improved clinical outcomes have been observed following treatment of MM patients with elotuzumab in combination with lenalidomide or bortezomib. Previous work showed that elotuzumab stimulates NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC), via Fc-domain engagement with FcγRIIIa (CD16). SLAMF7 is also expressed on NK cells, where it can transmit stimulatory signals...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28883264/treatment-algorithms-for-multiple-myeloma-in-japan
#15
Shuji Ozaki
Recent progress in the development of novel therapeutic agents has remarkably improved the treatment outcome for multiple myeloma (MM). Proteasome inhibitors such as bortezomib, carfilzomib, and ixazomib; immunomodulatory drugs (IMiDs) such as thalidomide, lenalidomide, and pomalidomide; the histone deacetylase (HDAC) inhibitor panobinostat; and the monoclonal antibody, elotuzumab, have all been approved in Japan, although only bortezomib and lenalidomide have been approved for initial therapy. Accordingly, the Japanese Society of Hematology has released updated treatment guidelines for MM...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28883263/combination-therapy-with-monoclonal-antibodies-for-treatment-of-newly-diagnosed-multiple-myeloma
#16
Noriko Nishimura, Yasuhito Terui, Kiyohiko Hatake
Monoclonal antibodies (mAbs) with new mechanisms of action are emerging as promising agents for patients with multiple myeloma (MM). Of these, anti-CD38 antibodies and anti-signaling lymphocytic activation molecule F7 (SLAMF7) antibody have demonstrated efficacy for relapsed and refractory myeloma (RRMM). Two CD38-targeting antibodies, daratumumab and isatuximab had significant activity as single agents, whereas the SLAMF7-targeting antibody, elotuzumab, did not. Patients with RRMM treated with 16 mg/kg daratumumab achieved at least PR of 36% and 29% in two distinct phase 2 studies...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28880973/a-new-monoclonal-protein-detected-in-a-patient-with-myeloma-undergoing-elotuzumab-therapy
#17
Felicia Tang, Christine Schmotzer, Rose C Beck
No abstract text is available yet for this article.
September 7, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28861320/cs1-slamf7-cd319-is-an-effective-immunotherapeutic-target-for-multiple-myeloma
#18
REVIEW
Joseph D Malaer, Porunelloor A Mathew
CS1 (also known as CD319, CRACC and SLAMF7) was identified as an NK cell receptor regulating immune functions. It is also expressed on B cells, T cells, Dendritic cells, NK-T cells, and monocytes. CS1 is overexpressed in multiple myeloma and makes it a target for immunotherapy. A humanized anti-CS1 antibody, Elotuzumab or Empliciti has shown promising results in clinical studies. This review focuses on the biology of CS1 in NK and other hematopoietic cells and multiple myeloma. Anti-CS1 mAb can activate natural cytotoxicity of NK cells as well as enhance ADCC (antibody-dependent cell-mediated cytotoxicity) and thus makes an effective target for immunotherapy of MM...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28857616/adoptive-cell-therapy-in-multiple-myeloma
#19
Sonia Vallet, Martin Pecherstorfer, Klaus Podar
Recent breakthrough advances in Multiple Myeloma (MM) immunotherapy have been achieved with the approval of the first two monoclonal antibodies, elotuzumab and daratumumab. Adoptive cell therapy (ACT) represents yet another, maybe the most powerful modality of immunotherapy, in which allogeneic or autologous effector cells are expanded and activated ex vivo followed by their re-infusion back into patients. Infused effector cells belong to two categories: naturally occurring, non-engineered cells (donor lymphocyte infusion, myeloma infiltrating lymphocytes, deltagamma T cells) or genetically- engineered antigen-specific cells (chimeric antigen receptor T or NK cells, TCR-engineered cells)...
September 6, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28747306/how-i-treat-myeloma-with-new-agents
#20
REVIEW
Philippe Moreau
At present, multiple classes of agents with distinct mechanisms of action are available for the treatment of patients with multiple myeloma (MM), including alkylators, steroids, immunomodulatory agents (IMiDs), proteasome inhibitors (PIs), histone deacetylase inhibitors (DACIs), and monoclonal antibodies (mAbs). Over the last 5 years, several new agents, such as the third-generation IMiD pomalidomide, the second-generation PIs carfilzomib and ixazomib, the DACI panobinostat, and 2 mAbs, elotuzumab and daratumumab, have been approved, incorporated into clinical guidelines, and have transformed our approach to the treatment of patients...
September 28, 2017: Blood
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