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Sagar Lonial - One of the best experts on this subject based on the ideXlab platform.
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extended 5 y follow up fu of phase 3 eloquent 2 study of Elotuzumab lenalidomide dexamethasone eld vs ld in relapsed refractory multiple myeloma rrmm
Journal of Clinical Oncology, 2018Co-Authors: Sagar Lonial, Maria-victoria Mateos, Meletios A. Dimopoulos, Philippe Moreau, Darrell White, Kenneth C Anderson, Katja Weisel, Jesus F Sanmiguel, Ofer Shpilberg, Sebastian GrosickiAbstract:8040Background: The immunostimulatory monoclonal antibody Elotuzumab exhibits a dual mechanism of action, directly activating natural killer cells and mediating myeloma cell death via antibody-depe...
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Managing Infusion Reactions to New Monoclonal Antibodies in Multiple Myeloma: Daratumumab and Elotuzumab.
Journal of oncology practice, 2018Co-Authors: Ajay K. Nooka, Charise Gleason, Marva Ollivierre Sargeant, Michelle Walker, Melanie Watson, Elyse Hall Panjic, Sagar LonialAbstract:Monoclonal antibodies (Elotuzumab and daratumumab) are the newest class of drugs that have proven to be efficacious antimyeloma agents. Although daratumumab, a CD38 monoclonal antibody, has established its efficacy as a single agent and in combination with immunomodulatory agents and proteasome inhibitors, Elotuzumab (signaling lymphocytic activation molecule F7 monoclonal antibody) has proven activity in combination with lenalidomide and dexamethasone. Infusion-related reactions (respiratory and nonrespiratory) seem to be a common theme of adverse events with monoclonal antibodies, although the relative incidence differs across these two agents. Identifying the appropriate pre- and postinfusion medication strategies can help lower the rates of infusion-related reactions and facilitate reduction in infusion times. In this article, we review the incidence of the infusion-related reactions with Elotuzumab and daratumumab and their clinical activity in myeloma, review our institutional experience of management of infusion-related reactions, and provide some practical mitigation strategies to reduce their incidence.
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phase 3 eloquent 2 study extended four year follow up fu of Elotuzumab plus lenalidomide dexamethasone eld vs ld in relapsed refractory multiple myeloma rrmm
Journal of Clinical Oncology, 2017Co-Authors: Sagar Lonial, Maria-victoria Mateos, Meletios A. Dimopoulos, Philippe Moreau, Jesus San F Miguel, Darrell White, Kenneth C Anderson, Katja Weisel, Ofer Shpilberg, Sebastian GrosickiAbstract:8028Background: Elotuzumab, an immunostimulatory monoclonal antibody, has a dual mechanism of action: directly activating NK cells and tagging myeloma cells for recognition/death via antibody-depen...
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How to Integrate Elotuzumab and Daratumumab Into Therapy for Multiple Myeloma
Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2016Co-Authors: Craig C Hofmeister, Sagar LonialAbstract:Purpose Treatment options and outcomes for patients with multiple myeloma have dramatically improved over the past decade with new agents and drug targets for patients at all stages of disease. Incorporation of newly approved monoclonal antibodies is a clinical challenge because the trials used to gain approval are relatively limited in scope and may be less helpful for patients treated in the United States. This article will review data on the use of Elotuzumab and daratumumab and provide a foundation for their use in current clinical practice. Methods We performed a review of current published articles and abstract data from clinical trials as well as data on managing adverse events. Results Single-agent activity was seen when using daratumumab in refractory myeloma, and trials for both Elotuzumab and daratumumab have demonstrated significant activity when combined with proteasome inhibitors and immunomodulatory agents. Unique antibody-related adverse events and challenges are reviewed and discussed. Conclusion These antibodies already have had and will continue to have a dramatic impact on myeloma treatment. Combination therapy likely represents the best approach for their use, and trials that evaluate optimal timing and duration of therapy are in progress as part of induction, salvage, and maintenance therapy.
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update on Elotuzumab a novel anti slamf7 monoclonal antibody for the treatment of multiple myeloma
Expert Opinion on Biological Therapy, 2016Co-Authors: Sagar Lonial, Maria-victoria Mateos, Jonathan L Kaufman, Jacob P Laubach, Donna E Reece, Paul G RichardsonAbstract:ABSTRACTIntroduction: In 2015, 4 new drugs were approved for the treatment of patients with multiple myeloma who experience drug resistance and relapsing disease, offering potential for improved patient outcomes. Given the mortality, morbidity, and projected rise in the incidence of multiple myeloma, more effective, novel therapies and treatment combinations are needed for patients at each stage of the disease.Areas covered: Here, the authors examine published data regarding the development and clinical investigation of Elotuzumab, a SLAMF7-targeted monoclonal antibody, for treatment of patients with multiple myeloma. The clinical efficacy, safety, and tolerability of Elotuzumab treatment are summarized.Expert opinion: Elotuzumab, a first-in-class immunostimulatory monoclonal antibody, is indicated in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received 1–3 prior therapies. Elotuzumab has the potential for use in patients in the upfront sett...
Philippe Moreau - One of the best experts on this subject based on the ideXlab platform.
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update on Elotuzumab for the treatment of relapsed refractory multiple myeloma patients selection and perspective
OncoTargets and Therapy, 2019Co-Authors: Sabrina Trudel, Philippe Moreau, Cyrille TouzeauAbstract:Monoclonal antibodies (mAbs) targeting antigens expressed by plasma cells demonstrated major clinical activity in multiple myeloma patients and therefore became a new major class of drug for these patients. Elotuzumab is a humanized mAb targeting the cell surface signaling lymphocytic activation molecule family member 7, a glycoprotein highly expressed on plasma cells, that is the second mAb approved for the treatment of myeloma patients. The mechanism of action of Elotuzumab includes natural killer cell (NK) mediated antibody-dependent cellular cytotoxicity and direct activation of NK-cells. Elotuzumab has been approved in combination with lenalidomide and dexamethasone (Elo-Rd) and pomalidomide and dexamethasone (Elo-Pd) for the treatment of relapsed myeloma patients. The present review will focus on Elotuzumab, providing a summary of the mechanism of action, efficacy and safety and taking into consideration patients' selection.
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Elotuzumab plus pomalidomide and dexamethasone for multiple myeloma
The New England Journal of Medicine, 2018Co-Authors: Meletios A. Dimopoulos, Mitsuo Hori, Kenshi Suzuki, Xavier Leleu, Philippe Moreau, Dominik Dytfeld, Sebastian Grosicki, Naoki Takezako, Richard Leblanc, Marc S RaabAbstract:Abstract Background The immunostimulatory monoclonal antibody Elotuzumab plus lenalidomide and dexamethasone has been shown to be effective in patients with relapsed or refractory multiple myeloma....
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extended 5 y follow up fu of phase 3 eloquent 2 study of Elotuzumab lenalidomide dexamethasone eld vs ld in relapsed refractory multiple myeloma rrmm
Journal of Clinical Oncology, 2018Co-Authors: Sagar Lonial, Maria-victoria Mateos, Meletios A. Dimopoulos, Philippe Moreau, Darrell White, Kenneth C Anderson, Katja Weisel, Jesus F Sanmiguel, Ofer Shpilberg, Sebastian GrosickiAbstract:8040Background: The immunostimulatory monoclonal antibody Elotuzumab exhibits a dual mechanism of action, directly activating natural killer cells and mediating myeloma cell death via antibody-depe...
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phase 3 eloquent 2 study extended four year follow up fu of Elotuzumab plus lenalidomide dexamethasone eld vs ld in relapsed refractory multiple myeloma rrmm
Journal of Clinical Oncology, 2017Co-Authors: Sagar Lonial, Maria-victoria Mateos, Meletios A. Dimopoulos, Philippe Moreau, Jesus San F Miguel, Darrell White, Kenneth C Anderson, Katja Weisel, Ofer Shpilberg, Sebastian GrosickiAbstract:8028Background: Elotuzumab, an immunostimulatory monoclonal antibody, has a dual mechanism of action: directly activating NK cells and tagging myeloma cells for recognition/death via antibody-depen...
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clinical efficacy and management of monoclonal antibodies targeting cd38 and slamf7 in multiple myeloma
Blood, 2016Co-Authors: Niels W C J Van De Donk, Antonio Palumbo, Pieter Sonneveld, Maria-victoria Mateos, Philippe Moreau, Jacob P Laubach, Torben Plesner, Fabio Malavasi, Herve Avetloiseau, Henk M LokhorstAbstract:Immunotherapeutic strategies are emerging as promising therapeutic approaches in multiple myeloma (MM), with several monoclonal antibodies in advanced stages of clinical development. Of these agents, CD38-targeting antibodies have marked single agent activity in extensively pretreated MM, and preliminary results from studies with relapsed/refractory patients have shown enhanced therapeutic efficacy when daratumumab and isatuximab are combined with other agents. Furthermore, although Elotuzumab (anti-SLAMF7) has no single agent activity in advanced MM, randomized trials in relapsed/refractory MM have demonstrated significantly improved progression-free survival when Elotuzumab is added to lenalidomide-dexamethasone or bortezomib-dexamethasone. Importantly, there has been no significant additive toxicity when these monoclonal antibodies are combined with other anti-MM agents, other than infusion-related reactions specific to the therapeutic antibody. Prevention and management of infusion reactions is important to avoid drug discontinuation, which may in turn lead to reduced efficacy of anti-MM therapy. Therapeutic antibodies interfere with several laboratory tests. First, interference of therapeutic antibodies with immunofixation and serum protein electrophoresis assays may lead to underestimation of complete response. Strategies to mitigate interference, based on shifting the therapeutic antibody band, are in development. Furthermore, daratumumab, and probably also other CD38-targeting antibodies, interfere with blood compatibility testing and thereby complicate the safe release of blood products. Neutralization of the therapeutic CD38 antibody or CD38 denaturation on reagent red blood cells mitigates daratumumab interference with transfusion laboratory serologic tests. Finally, therapeutic antibodies may complicate flow cytometric evaluation of normal and neoplastic plasma cells, since the therapeutic antibody can affect the availability of the epitope for binding of commercially available diagnostic antibodies.
Paul G Richardson - One of the best experts on this subject based on the ideXlab platform.
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daratumumab Elotuzumab and the development of therapeutic monoclonal antibodies in multiple myeloma
Clinical Pharmacology & Therapeutics, 2017Co-Authors: Jacob P Laubach, Paul G Richardson, C Paba E Prada, Dan L LongoAbstract:There has been substantial progress in clinical outcomes for patients with multiple myeloma (MM). This encouraging trend derives in large part from the increasing number of effective therapeutic options and the ability because of this to achieve higher quality responses to treatment. The approval of both daratumumab and of Elotuzumab in combination with lenalidomide and dexamethasone, in late 2015, was a notable achievement in the field, as daratumumab and Elotuzumab represent the first monoclonal antibodies available for use in MM. Given their unique mechanisms of action and favorable side effect profiles, daratumumab and Elotuzumab have considerable potential as therapeutic partners with agents in other drug classes and in different clinical settings ranging from newly diagnosed to relapsed disease. This review discusses the development of daratumumab and Elotuzumab as well as other monoclonal antibodies currently being evaluated for use in MM.
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update on Elotuzumab a novel anti slamf7 monoclonal antibody for the treatment of multiple myeloma
Expert Opinion on Biological Therapy, 2016Co-Authors: Sagar Lonial, Maria-victoria Mateos, Jonathan L Kaufman, Jacob P Laubach, Donna E Reece, Paul G RichardsonAbstract:ABSTRACTIntroduction: In 2015, 4 new drugs were approved for the treatment of patients with multiple myeloma who experience drug resistance and relapsing disease, offering potential for improved patient outcomes. Given the mortality, morbidity, and projected rise in the incidence of multiple myeloma, more effective, novel therapies and treatment combinations are needed for patients at each stage of the disease.Areas covered: Here, the authors examine published data regarding the development and clinical investigation of Elotuzumab, a SLAMF7-targeted monoclonal antibody, for treatment of patients with multiple myeloma. The clinical efficacy, safety, and tolerability of Elotuzumab treatment are summarized.Expert opinion: Elotuzumab, a first-in-class immunostimulatory monoclonal antibody, is indicated in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received 1–3 prior therapies. Elotuzumab has the potential for use in patients in the upfront sett...
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a randomized phase 2 study of pomalidomide dexamethasone with or without Elotuzumab in patients with relapsed refractory multiple myeloma
Journal of Clinical Oncology, 2016Co-Authors: Jesus San F Miguel, Marc S Raab, Eric Bleickardt, Hartmut Goldschmidt, Sagar Lonial, Paul G Richardson, Suresh Shelat, Antonio PalumboAbstract:TPS8066Background: Therapies for multiple myeloma (MM) can slow progression, prolong survival, and reduce symptoms although most patients will relapse. Elotuzumab, a humanized IgG1 immunostimulatory monoclonal antibody targeting SLAMF7, is FDA approved in combination with lenalidomide and dexamethasone in patients with MM who have received 1 to 3 prior therapies; approval was based on the results of the Phase 3 ELOQUENT-2 trial.1 Clinical trials have shown minimal added toxicity when Elotuzumab is combined with the immunomodulatory drugs lenalidomide and thalidomide.1,2 Preclinical results of the OPM-2 xenograft model in ICR-SCID mice (previously used to show synergy of lenalidomide and Elotuzumab) demonstrated that the combination of Elotuzumab and pomalidomide synergize to kill tumor cells in vivo. Methods: This Phase 2, open-label, randomized study (NCT02654132) will evaluate the efficacy of Elotuzumab in combination with pomalidomide and dexamethasone vs pomalidomide and dexamethasone alone. Patients ...
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a randomized phase 2 study of pomalidomide dexamethasone with or without Elotuzumab in patients with relapsed refractory multiple myeloma
Journal of Clinical Oncology, 2016Co-Authors: Jesus San F Miguel, Marc S Raab, Eric Bleickardt, Hartmut Goldschmidt, Sagar Lonial, Paul G Richardson, Suresh Shelat, Antonio PalumboAbstract:TPS8066Background: Therapies for multiple myeloma (MM) can slow progression, prolong survival, and reduce symptoms although most patients will relapse. Elotuzumab, a humanized IgG1 immunostimulator...
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Elotuzumab in combination with lenalidomide and dexamethasone in patients with relapsed multiple myeloma final phase 2 results from the randomised open label phase 1b 2 dose escalation study
The Lancet Haematology, 2015Co-Authors: Paul G Richardson, Philippe Moreau, Marc S Raab, Darrell White, Andrzej Jakubowiak, Ravi Vij, Thierry Facon, Sundar Jagannath, Donna Reece, Lotfi BenboubkerAbstract:Summary Background Elotuzumab, an immunostimulatory monoclonal antibody targeting signalling lymphocytic activation molecule (SLAM) family member 7 (SLAMF7), selectively kills SLAMF7-expressing myeloma cells through direct activation and engagement of the innate immune system, and thus might have clinical benefit in the treatment of myeloma. In phase 1 of this phase 1b–2 study, 82% of patients with relapsed multiple myeloma who were given Elotuzumab plus lenalidomide and dexamethasone achieved an overall response. Here we report the final phase 2 results. Methods We did this randomised, multicentre, open-label, dose-escalation study (1703) at 17 hospitals in the USA, Canada, France, and Germany. Patients aged at least 18 years with confirmed, relapsed multiple myeloma, Eastern Cooperative Oncology Group performance status 0–2, and one to three previous therapies but no previous lenalidomide were eligible for phase 2. We randomly assigned patients (1:1) to either 10 mg/kg or 20 mg/kg intravenous Elotuzumab plus oral lenalidomide (25 mg) and dexamethasone (40 mg). We stratified patients on the basis of the number of previous therapies (one versus two or three), and status of previous treatment with immunomodulatory drugs (yes or no), and used permuted block randomisation with a block size of four. Treatment was given in 28-day cycles until disease progression or unacceptable toxic effects occurred (Elotuzumab was given on days 1, 8, 15, and 22 for cycles 1 to 2 and days 1 and 15 for subsequent cycles; lenalidomide was given on days 1–21 and dexamethasone once per week). The primary endpoint was the proportion of patients who achieved an objective response according to International Myeloma Working Group criteria. Primary analyses were done in the intention-to-treat population, and safety was analysed in all patients who received at least one dose of study drugs. This study is registered with ClinicalTrials.gov, number NCT00742560. Findings Between Jan 4, 2010, and Dec 21, 2010, we recruited and randomly assigned 73 patients to Elotuzumab (36 to 10 mg/kg, 37 to 20 mg/kg). At data cutoff (Jan 16, 2014), 13 patients remained on treatment (six on 10 mg/kg, seven on 20 mg/kg). 61 (84%) patients achieved an objective response (33 [92%] with 10 mg/kg, 28 [76%] with 20 mg/kg); 31 (42%) a very good partial response (17 [47%] with 10 mg/kg, 14 [38%] with 20 mg/kg); and 20 (27%) a partial response (10 [28%] with 10 mg/kg, 10 [27%] with 20 mg/kg). The most common treatment-emergent adverse events of any grade were diarrhoea (48 [66%]), muscle spasms (45 [62%]), and fatigue (41 [56%]). 57 (78%) patients had grade 3–4 events, the most common of which were lymphopenia (15 [21%]) and neutropenia (14 [19%]). Three deaths occurred, none related to the study drugs. Interpretation Elotuzumab combined with lenalidomide and dexamethasone in patients with relapsed multiple myeloma showed acceptable safety and efficacy that seems better than that previously noted with lenalidomide and dexamethasone only. Phase 3 trials are in progress. Funding Bristol-Myers Squibb, AbbVie Biotherapeutics.
Marc S Raab - One of the best experts on this subject based on the ideXlab platform.
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rationale and design of the german speaking myeloma multicenter group gmmg trial hd6 a randomized phase iii trial on the effect of Elotuzumab in vrd induction consolidation and lenalidomide maintenance in patients with newly diagnosed myeloma
BMC Cancer, 2019Co-Authors: Hans Salwender, Marc S Raab, Uta Bertsch, Katja Weisel, Jan Duerig, Christina Kunz, Axel Benner, Igor Wolfgang Blau, Jens Hillengass, Dirk HoseAbstract:Despite major advances in therapy, multiple myeloma is still an incurable malignancy in the majority of patients. To increase survival, deeper remissions (i.e. CR) translating into longer PFS need to be achieved. Incorporation of new drugs (i.e. bortezomib and lenalidomide) as induction and maintenance treatment in an intensified treatment concept, including high dose melphalan (200 mg/m2), has resulted in increased CR rates, and is considered the standard of care for younger patients. Elotuzumab in combination with lenalidomide and dexamethasone has given better results as lenalidomide and dexamethasone alone in a phase III trial. The GMMG-HD6 trial will be the first phase III trial investigating the role of Elotuzumab in combination with bortezomib, lenalidomide and dexamethasone (VRD) induction/consolidation and lenalidomide maintenance within a high dose concept. GMMG-HD6 is a randomized, open, multicenter phase III trial. The planned recruitment number is 564 NDMM patients. All patients will receive 4 VRD cycles as induction and undergo peripheral blood stem cell mobilization and harvesting. Thereafter they will be treated with high dose melphalan therapy plus autologous stem cell transplantation followed by 2 cycles of VRD consolidation and lenalidomide maintenance. Patients in arm B1 + B2 will additionally receive Elotuzumab in the induction phase, whereas patients in A2 + B2 will be treated with Elotuzumab added to consolidation and maintenance. The primary endpoint of the trial is PFS. Secondary objectives and endpoints are OS, CR rates after induction therapy comparing the two arms VRD (A1 + A2) vs VRD + Elotuzumab (B1 + B2), CR rates after consolidation treatment, best response to treatment during the study, time to progression (TTP), duration of response (DOR), toxicity and quality of life. Since this is the publication of a study protocol of an ongoing study, no results can be presented. This phase III trial is designed to evaluate whether the addition of Elotuzumab to an intensified treatment concept with high dose melphalan chemotherapy plus autologous stem cell transplantation and induction, consolidation and maintenance treatment with bortezomib and lenalidomide is able to improve PFS compared to the same concept without Elotuzumab. NCT02495922 on June 24th, 2015.
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Elotuzumab plus pomalidomide and dexamethasone for multiple myeloma
The New England Journal of Medicine, 2018Co-Authors: Meletios A. Dimopoulos, Mitsuo Hori, Kenshi Suzuki, Xavier Leleu, Philippe Moreau, Dominik Dytfeld, Sebastian Grosicki, Naoki Takezako, Richard Leblanc, Marc S RaabAbstract:Abstract Background The immunostimulatory monoclonal antibody Elotuzumab plus lenalidomide and dexamethasone has been shown to be effective in patients with relapsed or refractory multiple myeloma....
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a randomized phase 2 study of pomalidomide dexamethasone with or without Elotuzumab in patients with relapsed refractory multiple myeloma
Journal of Clinical Oncology, 2016Co-Authors: Jesus San F Miguel, Marc S Raab, Eric Bleickardt, Hartmut Goldschmidt, Sagar Lonial, Paul G Richardson, Suresh Shelat, Antonio PalumboAbstract:TPS8066Background: Therapies for multiple myeloma (MM) can slow progression, prolong survival, and reduce symptoms although most patients will relapse. Elotuzumab, a humanized IgG1 immunostimulatory monoclonal antibody targeting SLAMF7, is FDA approved in combination with lenalidomide and dexamethasone in patients with MM who have received 1 to 3 prior therapies; approval was based on the results of the Phase 3 ELOQUENT-2 trial.1 Clinical trials have shown minimal added toxicity when Elotuzumab is combined with the immunomodulatory drugs lenalidomide and thalidomide.1,2 Preclinical results of the OPM-2 xenograft model in ICR-SCID mice (previously used to show synergy of lenalidomide and Elotuzumab) demonstrated that the combination of Elotuzumab and pomalidomide synergize to kill tumor cells in vivo. Methods: This Phase 2, open-label, randomized study (NCT02654132) will evaluate the efficacy of Elotuzumab in combination with pomalidomide and dexamethasone vs pomalidomide and dexamethasone alone. Patients ...
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a randomized phase 2 study of pomalidomide dexamethasone with or without Elotuzumab in patients with relapsed refractory multiple myeloma
Journal of Clinical Oncology, 2016Co-Authors: Jesus San F Miguel, Marc S Raab, Eric Bleickardt, Hartmut Goldschmidt, Sagar Lonial, Paul G Richardson, Suresh Shelat, Antonio PalumboAbstract:TPS8066Background: Therapies for multiple myeloma (MM) can slow progression, prolong survival, and reduce symptoms although most patients will relapse. Elotuzumab, a humanized IgG1 immunostimulator...
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Elotuzumab in combination with lenalidomide and dexamethasone in patients with relapsed multiple myeloma final phase 2 results from the randomised open label phase 1b 2 dose escalation study
The Lancet Haematology, 2015Co-Authors: Paul G Richardson, Philippe Moreau, Marc S Raab, Darrell White, Andrzej Jakubowiak, Ravi Vij, Thierry Facon, Sundar Jagannath, Donna Reece, Lotfi BenboubkerAbstract:Summary Background Elotuzumab, an immunostimulatory monoclonal antibody targeting signalling lymphocytic activation molecule (SLAM) family member 7 (SLAMF7), selectively kills SLAMF7-expressing myeloma cells through direct activation and engagement of the innate immune system, and thus might have clinical benefit in the treatment of myeloma. In phase 1 of this phase 1b–2 study, 82% of patients with relapsed multiple myeloma who were given Elotuzumab plus lenalidomide and dexamethasone achieved an overall response. Here we report the final phase 2 results. Methods We did this randomised, multicentre, open-label, dose-escalation study (1703) at 17 hospitals in the USA, Canada, France, and Germany. Patients aged at least 18 years with confirmed, relapsed multiple myeloma, Eastern Cooperative Oncology Group performance status 0–2, and one to three previous therapies but no previous lenalidomide were eligible for phase 2. We randomly assigned patients (1:1) to either 10 mg/kg or 20 mg/kg intravenous Elotuzumab plus oral lenalidomide (25 mg) and dexamethasone (40 mg). We stratified patients on the basis of the number of previous therapies (one versus two or three), and status of previous treatment with immunomodulatory drugs (yes or no), and used permuted block randomisation with a block size of four. Treatment was given in 28-day cycles until disease progression or unacceptable toxic effects occurred (Elotuzumab was given on days 1, 8, 15, and 22 for cycles 1 to 2 and days 1 and 15 for subsequent cycles; lenalidomide was given on days 1–21 and dexamethasone once per week). The primary endpoint was the proportion of patients who achieved an objective response according to International Myeloma Working Group criteria. Primary analyses were done in the intention-to-treat population, and safety was analysed in all patients who received at least one dose of study drugs. This study is registered with ClinicalTrials.gov, number NCT00742560. Findings Between Jan 4, 2010, and Dec 21, 2010, we recruited and randomly assigned 73 patients to Elotuzumab (36 to 10 mg/kg, 37 to 20 mg/kg). At data cutoff (Jan 16, 2014), 13 patients remained on treatment (six on 10 mg/kg, seven on 20 mg/kg). 61 (84%) patients achieved an objective response (33 [92%] with 10 mg/kg, 28 [76%] with 20 mg/kg); 31 (42%) a very good partial response (17 [47%] with 10 mg/kg, 14 [38%] with 20 mg/kg); and 20 (27%) a partial response (10 [28%] with 10 mg/kg, 10 [27%] with 20 mg/kg). The most common treatment-emergent adverse events of any grade were diarrhoea (48 [66%]), muscle spasms (45 [62%]), and fatigue (41 [56%]). 57 (78%) patients had grade 3–4 events, the most common of which were lymphopenia (15 [21%]) and neutropenia (14 [19%]). Three deaths occurred, none related to the study drugs. Interpretation Elotuzumab combined with lenalidomide and dexamethasone in patients with relapsed multiple myeloma showed acceptable safety and efficacy that seems better than that previously noted with lenalidomide and dexamethasone only. Phase 3 trials are in progress. Funding Bristol-Myers Squibb, AbbVie Biotherapeutics.
Ravi Vij - One of the best experts on this subject based on the ideXlab platform.
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Elotuzumab plus pomalidomide and dexamethasone for relapsed refractory multiple myeloma initial data from a phase 2 non comparative study
Blood, 2018Co-Authors: Sundar Jagannath, Ravi Vij, Robert M Rifkin, Craig E Cole, Jesus G Berdeja, Michael A Thompson, Mihaela Popamckiver, Rao Saleem, William I BensingerAbstract:Abstract Introduction: Despite therapeutic advances, most patients (pts) with multiple myeloma (MM) eventually develop relapsed/refractory (RR) disease, and observational studies of pts refractory to immunomodulatory drugs and proteasome inhibitors have demonstrated a median overall survival (OS) of 13 mo (Kumar et al, Leukemia 2017;31:2443-8). Elotuzumab, an immunostimulatory monoclonal antibody targeted to SLAMF7, directly activates natural killer cells and mediates the killing of MM cells through antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis. Elotuzumab, combined with lenalidomide (len) and dexamethasone (dex), is indicated in the USA and EU for RRMM in pts who have received ≥1 prior therapy. Pomalidomide (pom), a 2nd-generation immunomodulatory drug, appears to synergize with Elotuzumab. The phase 2, randomized, international, exploratory ELOQUENT-3 study (NCT02654132) assessed Elotuzumab combined with pom and dex (EPd) vs pom and dex (Pd); after a minimum follow-up of 9 mo, median progression-free survival (PFS) with EPd was 10.3 vs 4.7 mo with Pd (hazard ratio=0.54) and the overall response rate (ORR) was 53% vs 26% (Dimopoulos et al, EHA 2018 [LB2606]). In this supportive study, with a minimum follow-up of 16 mo, we present initial efficacy and safety data for EPd in pts with relapsed and/or refractory MM. Methods: This phase 2, multicenter, non-comparative study (NCT02612779) enrolled pts ≥18 y of age with MM who were relapsed, refractory, or intolerant to len (received for ≥2 consecutive cycles), 1-2 prior therapies, disease progression during or after their last therapy, and with an Eastern Cooperative Oncology Group performance status of ≤2. Prior pom was not permitted. Pts received Elotuzumab 10 mg/kg IV weekly for the first two 28-d cycles and 20 mg/kg IV every 4 wk thereafter. Pom 4 mg orally was given on Days 1-21 of each cycle and dex 40 or 20 mg oral equivalent was given weekly for pts ≤75 or >75 y of age, respectively. Primary endpoint was PFS; additional endpoints included OS, ORR, and safety. Results: At database lock (Apr 4, 2018), 68 pts had received EPd. At baseline, median age was 67 y, 35 pts (51%) were male, and 21 (31%) had International Staging System stage II-III disease. Median (range) prior number of therapies was 2 (1-5) and 34 pts (50%) were relapsed and refractory to their most recent therapy; 6 pts had received ≥3 prior therapies. Prior therapies included len (n=68, 100%), bortezomib (n=59, 87%), cyclophosphamide (n=20, 29%), carfilzomib (n=14, 21%), and autologous stem cell transplantation (n=38, 56%). At analysis, pts had received a median of 9 cycles of EPd and 13 (19%) were still on treatment. The most common reasons for discontinuation were disease progression (n=26, 38%) and maximum clinical benefit (n=10, 15%). Median PFS was 11.1 mo (Figure) and ORR was 51%. Overall, 9 pts (13%) achieved very good partial response or better, 26 (38%) achieved partial response, and 12 (18%) achieved minimal response. Median (95% CI) duration of response was 16.7 (11.3, not estimable [NE]) mo. Median time to first response was 1 mo, and to best response was 2.8 mo. Median (95% CI) OS was 22.4 (21.8, NE) mo. Pts with ≥2 prior therapies had a median (95% CI) PFS of 11.1 (5.6, 15.0) mo and an ORR of 46%. The most frequent all-cause non-hematologic adverse events (AEs) were fatigue (n=37, 54%), diarrhea (n=23, 34%), and upper respiratory tract infection (n=23, 34%); all-cause infections were reported in 47 pts (69%). No second primary malignancies were reported. The most common all-cause hematologic AE was neutropenia, reported in 24 pts (35%) and grade 3-4 in 11 (16%). Anemia was reported in 15 pts (22%) and was grade 3-4 in 4 (6%). Infusion reactions were reported in 5 pts (7%), all grade 1-2. In total, 7 pts (10%) experienced grade 5 AEs, 1 of which (pulmonary sepsis) was considered related to treatment. Overall, 11 pts (16%) experienced AEs leading to discontinuation. Conclusions: EPd was associated with a median PFS of 11.1 mo and ORR of 51% in pts with RRMM. Safety was consistent with prior reports of Elotuzumab and pom, with no new safety signals. These data, coupled with findings from the randomized ELOQUENT-3 study, support EPd as a new, effective treatment option for pts with RRMM. Study support: BMS. Medical writing: Adam Gill, Caudex, funded by BMS Download : Download high-res image (128KB) Download : Download full-size image Disclosures Jagannath: Merck: Consultancy; Bristol-Myers Squibb: Consultancy; Novartis: Consultancy; Celgene: Consultancy; Multiple Myeloma Research Foundation: Speakers Bureau; Medicom: Speakers Bureau. Berdeja: Teva: Research Funding; Glenmark: Research Funding; Amgen: Research Funding; Novartis: Research Funding; Takeda: Research Funding; Bristol-Myers Squibb: Research Funding; Celgene: Research Funding; Genentech: Research Funding; Janssen: Research Funding; Bluebird: Research Funding; Poseida Therapeutics, Inc.: Research Funding; Sanofi: Research Funding. Rifkin: Celgene: Consultancy; EMD Serono: Consultancy; Takeda: Consultancy; Sandoz: Consultancy; McKesson: Equity Ownership; Boehringer Ingelheim: Consultancy; Amgen: Consultancy. Cole: University of Michigan: Employment; Cancer Support Community myeloma advisory board: Membership on an entity's Board of Directors or advisory committees. Thompson: Syapse Precision Medicine Council: Other: Member; Strata Oncology: Membership on an entity's Board of Directors or advisory committees; VIA Oncology: Other: Co-Chair Medical Hematology ITP Committee, Co-Chair Medical Oncology Indolent Lymphoma Committee; Plasma Cell Dyscrasias: Patents & Royalties: Peer Review for Plasma Cell Dyscrasias (Editor: Robert Kyle); Glaxosmith Kline: Membership on an entity's Board of Directors or advisory committees; Takeda: Other: Multiple Myeloma Registry; AIM Specialty Health: Membership on an entity's Board of Directors or advisory committees; Celgene: Other: Connect MDS/AML Registry - Scientific Steering Committee Member. Vij: Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharma: Honoraria, Membership on an entity's Board of Directors or advisory committees; Jansson: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees. Popa-McKiver: Bristol-Myers Squibb: Employment. Saleem: Bristol-Myers Squibb: Employment. Sy: Bristol-Myers Squibb: Employment. Bensinger: Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Speakers Bureau; Amgen: Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.
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impact of Elotuzumab treatment on pain and health related quality of life in patients with relapsed or refractory multiple myeloma results from the eloquent 2 study
Annals of Hematology, 2018Co-Authors: David Cella, Antonio Palumbo, Ravi Vij, J Mckendrick, Amber Kudlac, Abderrahim Oukessou, Teresa Zyczynski, Catherine DavisAbstract:Treatment of relapsed/refractory multiple myeloma (RRMM) aims to prolong survival while maintaining health-related quality of life (HRQoL) by managing disease-related symptoms and complications—one of the most frequent and debilitating being bone pain. In the ELOQUENT-2 study (NCT01239797), which evaluated the addition of Elotuzumab to lenalidomide plus dexamethasone versus lenalidomide plus dexamethasone, pain and HRQoL were assessed in patients with relapsed/refractory disease using the Brief Pain Inventory–Short Form (BPI-SF) and the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire–Core 30 module (QLQ-C30) and myeloma-specific module (QLQ-MY20). Mean baseline pain scores were low and remained so throughout treatment with both regimens; mean HRQoL scores did not change substantially from baseline. A significantly higher proportion of patients with objective response than without had clinically meaningful improvements in worst pain over two consecutive treatment cycles (29 versus 12%; p < 0.001). Patients with very good partial response (VGPR) or better reported reduced scores for pain severity and worst pain; those with progressive disease reported increased scores for these domains and pain interference. These findings show that previously reported improvements in progression-free survival and response rate with Elotuzumab are achieved without detriment to HRQoL, which is maintained over time.
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an open label single arm phase iia study of bortezomib lenalidomide dexamethasone and Elotuzumab in newly diagnosed multiple myeloma
Journal of Clinical Oncology, 2017Co-Authors: Jacob P Laubach, Saad Z Usmani, Ravi Vij, Ajay K. Nooka, Craig E Cole, Elizabeth Odonnell, Gregory Orloff, Joshua R Richter, Robert A Redd, Heidi DipietroAbstract:8002Background: Elotuzumab (elo) is approved for use in combination with lenalidomide (len) and dexamethasone (dex) for relapsed and refractory multiple myeloma (MM). This phase 2a study evaluated ...
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Elotuzumab in combination with lenalidomide and dexamethasone in patients with relapsed multiple myeloma final phase 2 results from the randomised open label phase 1b 2 dose escalation study
The Lancet Haematology, 2015Co-Authors: Paul G Richardson, Philippe Moreau, Marc S Raab, Darrell White, Andrzej Jakubowiak, Ravi Vij, Thierry Facon, Sundar Jagannath, Donna Reece, Lotfi BenboubkerAbstract:Summary Background Elotuzumab, an immunostimulatory monoclonal antibody targeting signalling lymphocytic activation molecule (SLAM) family member 7 (SLAMF7), selectively kills SLAMF7-expressing myeloma cells through direct activation and engagement of the innate immune system, and thus might have clinical benefit in the treatment of myeloma. In phase 1 of this phase 1b–2 study, 82% of patients with relapsed multiple myeloma who were given Elotuzumab plus lenalidomide and dexamethasone achieved an overall response. Here we report the final phase 2 results. Methods We did this randomised, multicentre, open-label, dose-escalation study (1703) at 17 hospitals in the USA, Canada, France, and Germany. Patients aged at least 18 years with confirmed, relapsed multiple myeloma, Eastern Cooperative Oncology Group performance status 0–2, and one to three previous therapies but no previous lenalidomide were eligible for phase 2. We randomly assigned patients (1:1) to either 10 mg/kg or 20 mg/kg intravenous Elotuzumab plus oral lenalidomide (25 mg) and dexamethasone (40 mg). We stratified patients on the basis of the number of previous therapies (one versus two or three), and status of previous treatment with immunomodulatory drugs (yes or no), and used permuted block randomisation with a block size of four. Treatment was given in 28-day cycles until disease progression or unacceptable toxic effects occurred (Elotuzumab was given on days 1, 8, 15, and 22 for cycles 1 to 2 and days 1 and 15 for subsequent cycles; lenalidomide was given on days 1–21 and dexamethasone once per week). The primary endpoint was the proportion of patients who achieved an objective response according to International Myeloma Working Group criteria. Primary analyses were done in the intention-to-treat population, and safety was analysed in all patients who received at least one dose of study drugs. This study is registered with ClinicalTrials.gov, number NCT00742560. Findings Between Jan 4, 2010, and Dec 21, 2010, we recruited and randomly assigned 73 patients to Elotuzumab (36 to 10 mg/kg, 37 to 20 mg/kg). At data cutoff (Jan 16, 2014), 13 patients remained on treatment (six on 10 mg/kg, seven on 20 mg/kg). 61 (84%) patients achieved an objective response (33 [92%] with 10 mg/kg, 28 [76%] with 20 mg/kg); 31 (42%) a very good partial response (17 [47%] with 10 mg/kg, 14 [38%] with 20 mg/kg); and 20 (27%) a partial response (10 [28%] with 10 mg/kg, 10 [27%] with 20 mg/kg). The most common treatment-emergent adverse events of any grade were diarrhoea (48 [66%]), muscle spasms (45 [62%]), and fatigue (41 [56%]). 57 (78%) patients had grade 3–4 events, the most common of which were lymphopenia (15 [21%]) and neutropenia (14 [19%]). Three deaths occurred, none related to the study drugs. Interpretation Elotuzumab combined with lenalidomide and dexamethasone in patients with relapsed multiple myeloma showed acceptable safety and efficacy that seems better than that previously noted with lenalidomide and dexamethasone only. Phase 3 trials are in progress. Funding Bristol-Myers Squibb, AbbVie Biotherapeutics.
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phase ph i ii study of Elotuzumab elo plus lenalidomide dexamethasone len dex in relapsed refractory multiple myeloma rr mm updated ph ii results and ph i ii long term safety
Journal of Clinical Oncology, 2013Co-Authors: Sagar Lonial, Philippe Moreau, Marc S Raab, Eric Bleickardt, Donna E Reece, Andrzej Jakubowiak, Ravi Vij, Thierry Facon, Sundar Jagannath, Lotfi BenboubkerAbstract:8542 Background: Elotuzumab (Elo) is a humanized anti-CS1monoclonal antibody that enhances natural killer cell mediated antibody dependent cellular cytotoxicity of CS1 expressing myeloma cells. Thi...