1. Slideset on: Jakubowiak AJ, Benson DM, Bensinger W, et al. Phase I trial of anti-CS1 monoclonal antibody elotuzumab in combination with bortezomib in the treatment of relapsed/ refractory multiple myeloma. J Clin Oncol 2012;30:1960-1965. Elotuzumab and Bortezomib Combination Active, Safe in Relapsed/Refractory Multiple Myeloma This program is supported by educational grants from

2. clinicaloptions.com/oncology An Online Journal Club Resource for Physician Fellows  Elotuzumab [1,2] –Anti-CS1, humanized IgG1 –Elotuzumab binding to myeloma cells blocks adhesion to bone marrow stroma –Proposed mechanism is by NK-dependent ADCC  CS1 cell surface antigen [1,2] –High expression on MM cells, normal plasma cells –Low to no expression on normal cells –Intermediate expression on NK cells Elotuzumab Background 1. Hsi ED, et al. Clin Cancer Res. 2008;14:2775-2784. 2.Tai YT, et al. Blood. 2008;112:1329-1337.

3. clinicaloptions.com/oncology An Online Journal Club Resource for Physician Fellows Phase I Study Design  Criteria –Active disease, 1-3 previous therapies –No recent SCT, ≥ grade 2 neuropathy  Treatment (21-day cycle) –Bortezomib 1.3 mg/m 2 IV on Days 1, 4, 8, 11 –Elotuzumab at 1 of 4 escalating doses: 2.5, 5, 10, or 20 mg/kg IV on Days 1 and 11 –Given within 30 min of bortezomib  Primary objective: MTD –Secondary objectives: efficacy, safety, PD/PK Jakubowiak AJ, et al. J Clin Oncol. 2012;30:1960-1965.

4. clinicaloptions.com/oncology An Online Journal Club Resource for Physician Fellows  MTD not reached at 20 mg/kg (maximum planned dose) Patients (%) N = 28  Adverse events typically resolved spontaneously  Hypersensitivity in 1 patient Grade 3/4 toxicity Jakubowiak AJ, et al. J Clin Oncol. 2012;30:1960-1965. Elotuzumab/Bortezomib MTD and Safety 25 20 15 10 5 0 Lymphopenia Fatigue Neutropenia Thrombocytopenia Peripheral neuropathy Hyperglycemia

5. clinicaloptions.com/oncology An Online Journal Club Resource for Physician Fellows  ORR: 48% (13 of 27 evaluable patients) −67% in bortezomib-refractory disease (2 of 3 patients) −43% in lenalidomide-refractory disease (3 of 7 patients) −70% in high-risk cytogenetics (7 of 10 patients) −Response rates higher with fewer previous MM therapies  PD/PK −CS1 targets saturated to median 95% at 20 mg/kg −Peak elotuzumab serum levels ≥ 100 µg/mL at each dose −Elotuzumab serum trough levels, CS1 saturation not affected by added coadministration of bortezomib Jakubowiak AJ, et al. J Clin Oncol. 2012;30:1960-1965. Elotuzumab/Bortezomib Efficacy and PD/PK

6. clinicaloptions.com/oncology An Online Journal Club Resource for Physician Fellows Elotuzumab/Bortezomib Summary  MTD not reached at 20 mg/kg  48% ORR –Includes responses seen in bortezomib- and lenalidomide- refractory patients  CS1 targets saturated to median 95% at 20 mg/kg  Data suggest CS1 may be potentially useful target in multiple myeloma Jakubowiak AJ, et al. J Clin Oncol. 2012;30:1960-1965.