1. R1.이용석 / modulator pf.한재준

2. Introduction Multiple myeloma Combination therapy
malignant disease of monoclonal plasma cells (median overall survival of approximately 5 years)
most patients continue to have a relapse
new treatment approaches are needed
Combination therapy
Lenalidomide + dexamethasone
Stnadard therapy for relapsed or refractory disease
Three-drug combinations are previously treated multiple myeloma but may be limited by toxic effects
Agents with new mechanisms of action are needed

3. Introduction Elotuzumab
humanized immunoglobulin G1 immunostimulatory monoclonal antibody
targeted against signaling lymphocytic activation molecule F7 (SLAMF7, also called CS1[cell-surface glycoprotein CD2 subset 1]
glycoprotein expressed on myeloma and natural killer cells but not on normal tissues
dual effect by directly activating natural killer cells and mediating antibody-dependent cell-mediated cytotoxicity through the CD16 pathway.

4. Introduction
Elotuzumab

5. Method
Patient
18 years of age or older and had multiple myeloma and measurable disease.
All patients had received one to three previous therapies
disease progression after their most recent therapy.
CrCl : >30ml/min
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6. Method Randomization and Study Treatment
Elotuzumab group : Elotuzumab 10mg /Kg IV day 1, 8, 15, and 22 during the first two cycles
lenalidomide 25mg /day p.o. D1~D21
Dexamethasone 40 mg p.o. during the week without elotuzumab
Dexamethasone 8mg IV + 28 mg po the day of elotuzumab administration.
control group : lenalidomide 25 mg p.o. days 1~21 + dexamethasone 40mg p.o. days 1, 8, 15, and 22.
Patients received mandatory premedication before elotuzumab infusion along with thromboembolic prophylaxis
28-day cycles until disease progression, unacceptable toxicity,
or withdrawal of consent
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7. Method Randomization and Study Treatment Study end points
Randomization was stratified
the baseline β2-microglobulin level (<3.5 mg per
liter vs. ≥3.5 mg per liter)
the number of previous therapies (one vs. two or three)
Previous immunomodulatory drug therapy (none vs. thalidomide only or other)
Study end points
Primary end point
progression-free survival
overall response rate
Key secondary end point
overall survival
severity of pain or interference with daily life.
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8. Method Assessments Efficacy end points Tumor assessments
European Group for Blood and Marrow Transplantation
Tumor assessments
every 4 weeks after the first dose
Response criteria of the International Myeloma Working Group
until disease progression, death, or withdrawal of consent
Pain and health-related quality of life
the Brief Pain Inventory
European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire–Core 30 module(EORTC QLQ-C30)
myeloma-specific module (EORTC QLQ-MY20)
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9. Results

10. progression-free survival
Results
Median
progression-free survival
19.4 mo
14.9 mo

11. Results 179 events(165 progression, 14 death)

12. Results

13. Median duration of treatment
Results
Median duration of treatment
17 mo vs 12 mo

14. Conclusion The use of elotuzumab
an immunostimulatory monoclonal antibody targeting a cell-surface receptor
direct activation of natural killer cells
the capacity to trigger antibody-dependent cell- mediated cytotoxicity of myeloma cells
improved progression-free survival in patients with relapsed or refractory multiple myeloma