Elotuzumab Therapy for Relapsed or Refractory Multiple Myeloma
Open accessAbstract
BACKGROUND: Elotuzumab, an immunostimulatory monoclonal antibody targeting signaling lymphocytic activation molecule F7 (SLAMF7), showed activity in combination with lenalidomide and dexamethasone in a phase 1b-2 study in patients with relapsed or refractory multiple myeloma. METHODS: In this phase 3 study, we randomly assigned patients to receive either elotuzumab plus lenalidomide and dexamethasone (elotuzumab group) or lenalidomide and dexamethasone alone (control group). Coprimary end points were progression-free survival and the overall response rate. Final results for the coprimary end points are reported on the basis of a planned interim analysis of progression-free survival. RESULTS: Overall, 321 patients were assigned to the elotuzumab group and 325 to the control group. After a median follow-up of 24.5 months, the rate of progression-free survival at 1 year in the elotuzumab group was 68%, as compared with 57% in the control group; at 2 years, the rates were 41% and 27%, respectively. Median progression-free survival in the elotuzumab group was 19.4 months, versus 14.9 months in the control group (hazard ratio for progression or death in the elotuzumab group, 0.70; 95% confidence interval, 0.57 to 0.85; P<0.001). The overall response rate in the elotuzumab group was 79%, versus 66% in the control group (P<0.001). Common grade 3 or 4 adverse events in the two groups were lymphocytopenia, neutropenia, fatigue, and pneumonia. Infusion reactions occurred in 33 patients (10%) in the elotuzumab group and were grade 1 or 2 in 29 patients. CONCLUSIONS: Patients with relapsed or refractory multiple myeloma who received a combination of elotuzumab, lenalidomide, and dexamethasone had a significant relative reduction of 30% in the risk of disease progression or death. (Funded by Bristol-Myers Squibb and AbbVie Biotherapeutics; ELOQUENT-2 ClinicalTrials.gov number, NCT01239797.).
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Elotuzumab does not have single-agent activity but shows synergistic activity when combined with lenalidomide and dexamethasone (Rd).
“Unlike daratumumab, elotuzumab does not have single-agent activity but shows synergistic activity when combined with Rd (Table 8).84”
From Multiple myeloma: 2024 update on diagnosis, risk-stratification, and management (2024) · cites this paper as [84]
The Efficacy section (page unavailable in our copy) reports higher response rates with elotuzumab plus lenalidomide and dexamethasone than with lenalidomide and dexamethasone alone. That supports a benefit from adding elotuzumab, but the paper does not assess elotuzumab alone or establish that the combination is synergistic; searches for monotherapy and synergy found no such passage. (LLM, conf=0.86)
Experimental — accuracy not yet measuredElotuzumab targets SLAMF7, while daratumumab and isatuximab target CD38.
“Elotuzumab targets SLAMF7; daratumumab and isatuximab target CD38 respectively.84–87”
From Multiple myeloma: 2024 update on diagnosis, risk-stratification, and management (2024) · cites this paper as [84]
Daratumumab with lenalidomide and dexamethasone was associated with clinically manageable adverse events that were consistent with the known toxic effects of lenalidomide and dexamethasone and of daratumumab.
“Daratumumab with lenalidomide and dexamethasone was associated with clinically manageable adverse events that were consistent with the known toxic effects of lenalidomide and dexamethasone 27,28,30,31 and of daratumumab.9,10”
From Daratumumab, Lenalidomide, and Dexamethasone for Multiple Myeloma. (2016) · cites this paper as [30]
Elotuzumab has been proposed to function at least partially through upregulation of IL-2 production by T cells and stimulation of natural killer cell-mediated antibody-dependent cellular cytotoxicity.
“Elotuzumab has been proposed to function at least partially through upregulation of IL-2 production by T cells and stimulation of natural killer (NK) cell-mediated antibody-dependent cellular cytotoxicity (ADCC)68–70.”
From Cancer therapies based on targeted protein degradation — lessons learned with lenalidomide (2021) · cites this paper as [68]
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- Authors
- Lonial, S., Dimopoulos, M., Palumbo, A., White, D., Grosicki, S., Spicka, I., Walter-Croneck, A., Moreau, P., Mateos, M.-V., Magen, H., Belch, A., Reece, D., Beksac, M., Spencer, A., Oakervee, H., Orlowski, R. Z., Taniwaki, M., Röllig, C., Einsele, H., Wu, K. L., Singhal, A., San-Miguel, J., Matsumoto, M., Katz, J., Bleickardt, E., Poulart, V., Anderson, K. C., & Richardson, P.
- Affiliations
- Dalhousie University (CA)
- National and Kapodistrian University of Athens (GR)
- Azienda Ospedaliero Universitaria San Giovanni Battista (IT)
- Medical University of Silesia (PL)
- Centre Hospitalier Universitaire de Nantes (FR)
- Tel Aviv University (IL)
- University of Alberta (CA)
- Princess Margaret Cancer Centre (CA)
- Alfred Health (AU)
- Barts Health NHS Trust (GB)
- The University of Texas MD Anderson Cancer Center (US)
- Kyoto Prefectural University of Medicine (JP)
- Technische Universität Dresden (DE)
- Universitätsklinikum Würzburg (DE)
- Ziekenhuisnetwerk Antwerpen Stuivenberg (BE)
- AbbVie Biotherapeutics (United States) (US)
- National Hospital Organization (JP)
- Bristol-Myers Squibb (United States) (US)
- Dana-Farber Cancer Institute (US)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2015-08-13
- Volume
- 373
- Issue
- 7
- Pages
- 621-631
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2201190784
- Semantic Scholar
- fb9d8d9019089b66fbe8ecd85963014c537e649e
- Cited by
- 1,322
- References
- 15
- Citations by year
- 2026: 29 · 2025: 60 · 2024: 63 · 2023: 87 · 2022: 95 · 2021: 147 · 2020: 174 · 2019: 132 · 2018: 154 · 2017: 187 · 2016: 160 · 2015: 33
- FWCI
- 139.84
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion, other-oa)
- Funders
- Bristol-Myers Squibb
- AbbVie Biotherapeutics
- Topics
- Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Health Sciences › Medicine › Genetics › Chronic Lymphocytic Leukemia Research
- Keywords
- elotuzumab, relapsed/refractory multiple myeloma, SLAMF7, lenalidomide, dexamethasone, progression-free survival, overall response rate, monoclonal antibodies, combination therapy, adverse events, lymphopenia, neutropenia, infusion reactions, interim analysis, overall survival
- MeSH terms
- Signaling Lymphocytic Activation Molecule Family, Lenalidomide, Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols, Dexamethasone, Humans, Middle Aged, Multiple Myeloma, Receptors, Immunologic, Recurrence, Thalidomide, Disease-Free Survival, Antibodies, Monoclonal, Humanized
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