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REVIEW
Emily Chu, Jian Wu, Stacey S Kang, Yubin Kang
Multiple myeloma (MM) is a common hematological malignancy that has fostered several new therapeutic approaches to combat newly diagnosed or relapsed MM. While the field has advanced over the past 2 decades, the majority of patients will develop resistance to these treatments, causing the need for new therapeutic targets. SLAMF7 is an attractive therapeutic target in multiple myeloma, and a monoclonal antibody that targets SLAMF7 has shown consistent beneficial outcomes in clinical trials to date. In this review, we will focus on the structure and regulation of SLAMF7 and its mechanism of action...
August 27, 2023: Current Oncology
#22
MULTICENTER STUDY
Michael Slade, Mark A Fiala, Marie Kirchmeyer, Jeff King, Feng Gao, Mark A Schroeder, A Keith Stewart, Keith Stockerl-Goldstein, Christine Chen, Ravi Vij
Second autologous hematopoietic cell transplantation (AHCT2) is a useful therapeutic modality for fit patients with multiple myeloma who have durable remission after upfront AHCT. Retrospective studies have suggested a significant benefit of incorporating maintenance therapy post-AHCT2, but prospective data on specific regimens are lacking. The purpose of this study was to investigate the use of elotuzumab, pomalidomide, and dexamethasone (EPd) as salvage therapy prior to and maintenance after AHCT2 for relapsed multiple myeloma...
December 2023: Transplantation and cellular therapy
#23
JOURNAL ARTICLE
Jules T J Teuwen, Lucas F L Ritzen, Yvon M Knapen-Portz, Patricia K Ludwiczek, Jan G M C Damoiseaux, Joyce J B C van Beers, Douwe de Boer
Monoclonal gammopathies are characterized by the presence of monoclonal immunoglobulins, also known as M-proteins. Therapeutic monoclonal antibodies (t-mAbs) can interfere in laboratory assays used to monitor the state of disease, such as serum protein electrophoresis (SPE) and immunofixation electrophoresis (IFE). To establish a correct interpretation of IFE, Target protein-Collision Immunofixation Electrophoresis Reflex Assay (T-CIERA) was developed to identify t-mAbs in IFE. Here we demonstrate that T-CIERA is applicable to a wide variety of t-mAbs for which the target protein is commercially available...
August 29, 2023: Journal of Immunological Methods
#24
JOURNAL ARTICLE
Marwan Alrasheed, Abdulrahman Alsuhibani, Bander Balkhi, Jeff Jianfei Guo
INTRODUCTION: Multiple myeloma (MM) is the most common plasma cell tumor type. In late 2015, the FDA approved three new medications for MM. These medications were ixazomib, daratumumab, and elotuzumab. However, their utilization, reimbursement, and price in the Medicaid program have not been analyzed before. METHODS: A retrospective drug utilization study using the national Medicaid pharmacy claims data from 2016 to 2022 in the US. The primary metrics of analysis were utilization (number of prescriptions), reimbursement (total spending), and price (reimbursement per prescription)...
August 11, 2023: Healthcare (Basel, Switzerland)
#25
JOURNAL ARTICLE
Jan-Peter Grunz, Andreas Steven Kunz, Freerk T Baumann, Dirk Hasenclever, Malte Maria Sieren, Stefan Heldmann, Thorsten Alexander Bley, Hermann Einsele, Stefan Knop, Franziska Jundt
Multiple myeloma (MM) frequently induces persisting osteolytic manifestations despite hematologic treatment response. This study aimed to establish a biometrically valid study endpoint for bone remineralization through quantitative and qualitative analyses in sequential CT scans. Twenty patients (seven women, 58 ± 8 years) with newly diagnosed MM received standardized induction therapy comprising the anti-SLAMF7 antibody elotuzumab, carfilzomib, lenalidomide, and dexamethasone (E-KRd). All patients underwent whole-body low-dose CT scans before and after six cycles of E-KRd...
August 7, 2023: Cancers
#26
REVIEW
Antonio G Solimando, Markus Krebs, Vanessa Desantis, Donatello Marziliano, Ingrid Catalina Caradonna, Arcangelo Morizio, Antonella Argentiero, Endrit Shahini, Max Bittrich
Multiple myeloma (MM) is a cancerous condition characterized by the proliferation of plasma cells within the hematopoietic marrow, resulting in multiple osteolytic lesions. MM patients typically experience bone pain, kidney damage, fatigue due to anemia, and infections. Historically, MM was an incurable disease with a life expectancy of around three years after diagnosis. However, over the past two decades, the development of novel therapeutics has significantly improved patient outcomes, including response to treatment, remission duration, quality of life, and overall survival...
July 24, 2023: Biomedicines
#27
JOURNAL ARTICLE
Sara Petillo, Elena Sproviero, Luisa Loconte, Lorenzo Cuollo, Alessandra Zingoni, Rosa Molfetta, Cinzia Fionda, Alessandra Soriani, Cristina Cerboni, Maria Teresa Petrucci, Francesca Fazio, Rossella Paolini, Angela Santoni, Marco Cippitelli
Natural Killer (NK) cells act as important regulators in the development and progression of hematological malignancies and their suppressor activity against Multiple Myeloma (MM) cells has been confirmed in many studies. Significant changes in the distribution of NK cell subsets and dysfunctions of NK cell effector activities were described in MM patients and correlated with disease staging. Thus, restoring or enhancing the functionality of these effectors for the treatment of MM represents a critical need...
July 17, 2023: Cell Death & Disease
#28
JOURNAL ARTICLE
Massimo Gentile, Ernesto Vigna, Salvatore Palmieri, Monica Galli, Daniele Derudas, Roberto Mina, Roberta Della Pepa, Renato Zambello, Enrica Antonia Martino, Antonella Bruzzese, Silvia Mangiacavalli, Elena Zamagni, Catello Califano, Maurizio Musso, Concetta Conticello, Claudio Cerchione, Giuseppe Mele, Nicola Di Renzo, Massimo Offidani, Giuseppe Tarantini, Gloria Margiotta Casaluci, Angela Rago, Roberto Ria, Giuseppina Uccello, Gregorio Barilà, Gaetano Palumbo, Alessandra Pompa, Donatella Vincelli, Marino Brunori, Fabrizio Accardi, Valeria Amico, Angela Amendola, Raffaele Fontana, Velia Bongarzoni, Bernardo Rossini, Emilia Cotzia, Alessandro Gozzetti, Rita Rizzi, Nicola Sgherza, Eleonora Ferretti, Giuseppe Bertuglia, Davide Nappi, Maria Teresa Petrucci, Francesco Di Raimondo, Antonino Neri, Fortunato Morabito, Pellegrino Musto
In the ELOQUENT-3 trial, the combination of elotuzumab, pomalidomide and dexamethasone (EloPd) proved a superior clinical benefit over Pd with a manageable toxicity profile, leading to its approval in relapsed/refractory multiple myeloma (RRMM), who had received at least two prior therapies, including lenalidomide and a proteasome inhibitor (PI). We report here a real-world experience of 200 RRMMs treated with EloPd in 35 Italian centers outside of clinical trials. In our dataset, the median number of prior lines of therapy was 2, with 51% of cases undergoing autologous stem cell transplant (ASCT) and 73% exposed to daratumumab...
July 13, 2023: Haematologica
#29
JOURNAL ARTICLE
Haimin Chen, Haiqi Chen, Yan Zhou, Weiwei Xu, Jingjing Yu, Yao Xu, Fan Zhou
BACKGROUND: Although multiple myeloma is still incurable, an abundance of novel treatments have become available for relapsed and or refractory multiple myeloma (RRMM). Direct head-to-head comparisons between the novel treatments are lacking. We performed a network meta-analysis to evaluate immediate effects such as response quality of current novel-drugs combined therapeutic regimens, with the aim to identify treatments that could be more effective than others in RRMM. METHODS: We searched Cochrane Library, PubMed, Embase, and Web of Science for randomized controlled clinical trials receiving novel-drugs combined treatments as means of interventions...
December 2023: Hematology (Amsterdam, Netherlands)
#30
JOURNAL ARTICLE
Mahya Aghaee, Urszula Ledzewicz, Michael Robbins, Natalie Bezman, Hearn Jay Cho, Helen Moore
While many novel therapies have been approved in recent years for treating patients with multiple myeloma, there is still no established curative regimen, especially for patients with high-risk disease. In this work, we use a mathematical modeling approach to determine combination therapy regimens that maximize healthy lifespan for patients with multiple myeloma. We start with a mathematical model for the underlying disease and immune dynamics, which was presented and analyzed previously. We add the effects of three therapies to the model: pomalidomide, dexamethasone, and elotuzumab...
June 9, 2023: European Journal of Pharmaceutical Sciences
#31
REVIEW
Pooya Farhangnia, Shamim Mollazadeh Ghomi, Shabnam Mollazadehghomi, Hamid Nickho, Mahzad Akbarpour, Ali-Akbar Delbandi
The signaling lymphocytic activation molecule (SLAM) family receptors were discovered in immune cells for the first time. The SLAM-family receptors are a significant player in cytotoxicity, humoral immune responses, autoimmune diseases, lymphocyte development, cell survival, and cell adhesion. There is growing evidence that SLAM-family receptors have been involved in cancer progression and heralded as a novel immune checkpoint on T cells. Previous studies have reported the role of SLAMs in tumor immunity in various cancers, including chronic lymphocytic leukemia, lymphoma, multiple myeloma, acute myeloid leukemia, hepatocellular carcinoma, head and neck squamous cell carcinoma, pancreas, lung, and melanoma...
2023: Frontiers in Immunology
#32
JOURNAL ARTICLE
Manisha Bhutani, David M Foureau, Myra Robinson, Fei Guo, Kateryna Fesenkova, Shebli Atrash, Barry Paul, Cindy Varga, Reed Friend, Mauricio Pineda-Roman, Katherine Rigby, James T Symanowski, Sarah Norek, Mallory R Tucker, Lawrence J Druhan, Peter M Voorhees, Saad Z Usmani
INTRODUCTION: Treatment of patients with multiple myeloma (MM) in first relapse remains a challenge. This phase II study combined elotuzumab (Elo) with carfilzomib, lenalidomide, and dexamethasone (KRd) for treatment of MM in first relapse with the aim of improving efficacy. METHODS: Enrolled patients received Elo-KRd induction for 4 cycles, and Elo-lenalidomide maintenance until progression. The primary endpoint was VGPR or better (≥VGPR) postinduction. Secondary endpoints were MRD by flow cytometry, OS, PFS, and safety...
April 7, 2023: Clinical Lymphoma, Myeloma & Leukemia
#33
REVIEW
Upasana Ray, Robert Z Orlowski
Multiple myeloma is a malignancy of immunoglobulin-secreting plasma cells that is now often treated in the newly diagnosed and relapsed and/or refractory settings with monoclonal antibodies targeting lineage-specific markers used either alone or in rationally designed combination regimens. Among these are the anti-CD38 antibodies daratumumab and isatuximab, and the anti-Signaling lymphocytic activation molecule family member 7 antibody elotuzumab, all of which are used in their unconjugated formats. Single-chain variable fragments from antibodies also form a key element of the chimeric antigen receptors (CARs) in the B-cell maturation antigen (BCMA)-targeted CAR T-cell products idecabtagene vicleucel and ciltacabtagene autoleucel, which are approved in the advanced setting...
April 14, 2023: Pharmaceuticals
#34
JOURNAL ARTICLE
Shuang Xia, Hui Gong, Yichang Zhao, Lin Guo, Yikun Wang, Rui Ma, Bikui Zhang, Mayur Sarangdhar, Yoshihiro Noguchi, Miao Yan
Although some tumor lysis syndrome (TLS) cases have been reported with multiple myeloma patients taking monoclonal antibodies (mAbs), the association between TLS and mAbs remains mostly unknown. We aim to investigate the association between TLS and mAbs and describe clinical features. We conducted a disproportionality analysis to investigate the link between mAbs and TLS by excluding known confounders and compared with other anticancer drugs. The association between mAbs and TLS was evaluated using information component (IC)...
April 22, 2023: Clinical Pharmacology and Therapeutics
#35
JOURNAL ARTICLE
Klara Kropivsek, Paul Kachel, Sandra Goetze, Rebekka Wegmann, Yasmin Festl, Yannik Severin, Benjamin D Hale, Julien Mena, Audrey van Drogen, Nadja Dietliker, Joëlle Tchinda, Bernd Wollscheid, Markus G Manz, Berend Snijder
Multiple myeloma (MM) is a plasma cell malignancy defined by complex genetics and extensive patient heterogeneity. Despite a growing arsenal of approved therapies, MM remains incurable and in need of guidelines to identify effective personalized treatments. Here, we survey the ex vivo drug and immunotherapy sensitivities across 101 bone marrow samples from 70 patients with MM using multiplexed immunofluorescence, automated microscopy and deep-learning-based single-cell phenotyping. Combined with sample-matched genetics, proteotyping and cytokine profiling, we map the molecular regulatory network of drug sensitivity, implicating the DNA repair pathway and EYA3 expression in proteasome inhibitor sensitivity and major histocompatibility complex class II expression in the response to elotuzumab...
April 20, 2023: Nature Cancer
#36
JOURNAL ARTICLE
Yutaka Shimazu, Junya Kanda, Satoru Kosugi, Tomoki Ito, Hitomi Kaneko, Kazunori Imada, Yuji Shimura, Shin-Ichi Fuchida, Kentaro Fukushima, Hirokazu Tanaka, Satoshi Yoshihara, Kensuke Ohta, Nobuhiko Uoshima, Hideo Yagi, Hirohiko Shibayama, Ryosuke Yamamura, Yasuhiro Tanaka, Hitoji Uchiyama, Yoshiyuki Onda, Yoko Adachi, Hitoshi Hanamoto, Ryoichi Takahashi, Mitsuhiro Matsuda, Takashi Miyoshi, Teruhito Takakuwa, Masayuki Hino, Naoki Hosen, Shosaku Nomura, Chihiro Shimazaki, Itaru Matsumura, Akifumi Takaori-Kondo, Junya Kuroda
Novel therapeutic drugs have dramatically improved the overall survival of patients with multiple myeloma. We sought to identify the characteristics of patients likely to exhibit a durable response to one such drug, elotuzumab, by analyzing a real-world database in Japan. We analyzed 179 patients who underwent 201 elotuzumab treatments. The median time to next treatment (TTNT) with the 95% confidence interval was 6.29 months (5.18-9.20) in this cohort. Univariate analysis showed that patients with any of the following had longer TTNT: no high risk cytogenic abnormalities, more white blood cells, more lymphocytes, non-deviated κ/λ ratio, lower β2 microglobulin levels (B2MG), fewer prior drug regimens, no prior daratumumab use and better response after elotuzumab treatment...
March 29, 2023: Scientific Reports
#37
JOURNAL ARTICLE
Katja Weisel, Meletios A Dimopoulos, Jesús San-Miguel, Agne Paner, Monika Engelhardt, Fiona Taylor, Jennifer Lord-Bessen, Christine Yip, Mike Greenwood, Jackson Tang, Michele Cavo
Triplet regimens containing immunomodulatory drugs and proteasome inhibitors (PIs) have improved outcomes and extended survival for patients with relapsed/refractory multiple myeloma (RRMM). We evaluated updated health-related quality of life (HRQoL) findings from the phase 2 ELOQUENT-3 clinical trial (NCT02654132) after 4 years of treatment with elotuzumab plus pomalidomide and dexamethasone (EPd) and assessed the impact of the addition of elotuzumab on patients' HRQoL. HRQoL was assessed as an exploratory endpoint using the MD Anderson Symptom Inventory for Multiple Myeloma (MDASI-MM), which evaluates symptom severity, symptom interference, and HRQoL, and the 3-level EQ-5D, a patient-reported measure of health utility and general health...
March 2023: HemaSphere
#38
REVIEW
Fabiola De Luca, Alessandro Allegra, Carla Di Chio, Santo Previti, Maria Zappalà, Roberta Ettari
Multiple myeloma (MM) is a currently incurable hematologic cancer. This disease is characterized by immunological alterations of myeloid cells and lymphocytes. The first-line therapy involves the use of classic chemotherapy; however, many patients have a relapsed form that could evolve into a refractory MM. The new therapeutic frontiers involve the use of new monoclonal antibodies (Mab) such as daratumumab, isatuximab, and elotuzumab. In addition to monoclonal antibodies, new immunotherapies based on modern bispecific antibodies and chimeric antigen receptor (CAR) T cell therapy have been investigated...
February 5, 2023: International Journal of Molecular Sciences
#39
JOURNAL ARTICLE
Maryam Noori, Farimah Fayyaz, Nima Rezaei
OBJECTIVE: We evaluate the efficacy and safety of Elotuzumab, an immunostimulatory monoclonal antibody, in combination with concomitant treatment regimens for multiple myeloma (MM) patients. RESEARCH DESIGN AND METHODS: PubMed, Scopus, Web of Science, and EMBASE databases were searched systematically up to 2 August 2022. RESULTS: Five randomized control trials with a total of 1,763 participants were included. Elotuzumab combination therapy improved PFS and OS by 14% (hazard ratio [HR] 0...
March 2023: Expert Review of Anticancer Therapy
#40
JOURNAL ARTICLE
Maral DerSarkissian, Holly Cranmer, Jonathan Dabora, Iryna Bocharova, Dasha Cherepanov, Mu Cheng, Rachel H Bhak, Mei Sheng Duh
OBJECTIVES: In the absence of head-to-head comparisons across relapsed/refractory multiple myeloma (RRMM) treatments following the approval of the oral proteasome inhibitor ixazomib, in combination with lenalidomide and dexamethasone (IRd), we conducted an indirect comparison of the efficacy of IRd relative to several RRMM therapies using Bayesian fixed-effects network meta-analysis (NMA) models. METHODS: Data for the NMA were obtained through a systematic literature review (conducted in June 2020), which identified randomized controlled trials (base case) and observational studies (extended network analysis) reporting overall survival (OS), progression-free survival (PFS), and overall response rate (ORR)...
December 2023: Hematology (Amsterdam, Netherlands)
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