Quadruple Therapy With Elotuzumab + RVD in Newly Diagnosed MM: Phase IIa Study CCO Independent Conference Highlights* of the 2017 ASCO Annual Meeting; June 2-6, 2017; Chicago, Illinois *Clinical Care Options (CCO) is an independent medical education organization that provides conference coverage and other unique educational programs for healthcare professionals MM, multiple myeloma; RVD, lenalidomide/bortezomib/dexamethasone. This activity is supported by educational grants from AbbVie, Amgen, AstraZeneca, Celgene Corporation, Genentech, Halozyme, Incyte, and Merck & Co., Inc.

Elotuzumab + RVD in ND MM: Background Elotuzumab: humanized IgG1 mAb to plasma, NK cell antigen SLAM7[1] FDA approved for use with lenalidomide + dexamethasone in R/R MM[2,3] In pts with ND MM, RVD achieved superior PFS, OS vs lenalidomide + dexamethasone in phase III SWOG S0777 trial[4] In phase I SWOG S1211 trial, addition of elotuzumab to RVD as induction therapy found to be safe in pts with ND MM[5] Current phase IIa trial evaluated efficacy, safety of elotuzumab + RVD in transplant-eligible pts with ND MM[6] MM, multiple myeloma; ND, newly diagnosed; NK, natural killer; R/R, relapsed/refractory; RVD, lenalidomide/bortezomib/dexamethasone. 1. Hsi ED, et al. Clin Cancer Res. 2008;14:2775-2784. 2. Lonial S, et al. N Engl J Med. 2015;373:621-631. 3. Elotuzumab [package insert]. 2017. 4. Durie BG, et al. Lancet. 2017;389:519-527. 5. Usmani SZ, et al. Blood Cancer J. 2015;5:e334. 6. Laubach J, et al. ASCO 2017. Abstract 8002. Slide credit: clinicaloptions.com

Elotuzumab + RVD in ND MM: Study Design Open-label, single-arm phase IIa study Risk-Adapted Maintenance‡ (28-day cycles) Immediate ASCT Pts with newly diagnosed MM eligible for ASCT; measurable disease; ECOG PS 0-2 (N = 40) Elotuzumab* + RVD Induction† (four 21-day cycles) Follow-up every 3 mos until PD Elotuzumab* + RVD Induction† 4 cycles, then Risk-Adapted Maintenance‡ (28-day cycles) Deferred ASCT *ELO: 10 mg/kg IV on Day 1, 8, 15 for cycles 1, 2 and Day 1, 11 thereafter. †Len: 25 mg PO Days 1-14; Bort: 1.3 mg/m2 SC on Day 1, 4, 8, 11; Dex: 20 mg PO Day 2, 4, 5, 9, 11, 12, and 28 mg PO before ELO infusion; 8 mg IV Day 1, 8, 15 before ELO infusion. ASCT, autologous stem cell transplantation; Bort, bortezomib; Dex, dexamethasone; ELO, elotuzumab; ISS, International Staging System; Len, lenalidomide; MM, multiple myeloma; ND, newly diagnosed; PD, progressive disease; RVD, lenalidomide/bortezomib/dexamethasone. ‡High risk (ISS stage III and/or high-risk cytogenetics): ELO + RVD; standard risk (ISS stage I/II w/o high-risk cytogenetics): ELO + Len/Dex. Primary objective: response rate after 4 cycles of ELO + RVD Secondary objectives: proportion of pts with SC mobilization after 4 cycles ELO + RVD; proportion with dose modification within 4 cycles ELO + RVD; safety; clinical activity Slide credit: clinicaloptions.com Laubach J, et al. ASCO 2017. Abstract 8002.

Elotuzumab + RVD in ND MM: Risk-Adapted Maintenance Strategies Pts With ASCT Pts Deferring ASCT High risk: ISS stage III and/or high-risk cytogenetics High Risk: ISS Stage III and/or high-risk cytogenetics Elotuzumab: 20 mg/kg IV on Day 1 Bortezomib: 1.3 mg/m2 SC on Day 1, 15 Lenalidomide: 10 mg PO Days 1-21, then 7-day rest Dexamethasone: 8 mg IV Day 1 before elotuzumab infusion Lenalidomide: dose tolerated during induction; PO Days 1-21, then 7-day rest Standard risk: ISS stage I or II without high-risk cytogenetics Lenalidomide: dose tolerated during induction; PO Day 1-21, then 7-day rest ASCT, autologous stem cell transplantation; ISS, International Staging System; MM, multiple myeloma; ND, newly diagnosed; PCP, Pneumocystis pneumonia; RVD, lenalidomide/bortezomib/dexamethasone. All pts received antiviral prophylaxis; PCP prophylaxis recommended Slide credit: clinicaloptions.com Laubach J, et al. ASCO 2017. Abstract 8002.

Elotuzumab + RVD in ND MM: Baseline Characteristics Pts (N = 40) Median age, yrs (range) ≤ 60 yrs, n (%) > 60 yrs, n (%) 60 (34-75) 20 (50) Female, n (%) 17 (42) Race, n (%) Black White Other 7 (18) 3 (8) 30 (75) ISS stage, n (%) I II III 24 (60) 10 (25) 6 (15) Characteristic Pts (N = 40) Unfavorable cytogenetics, n/N (%) 6/39 (15) Unfavorable abnormalities, n (%) t(4:14) t(14:16) del(17p) 4 (10) 1 (3) MM, multiple myeloma; ND, newly diagnosed; RVD, lenalidomide/bortezomib/dexamethasone. Slide credit: clinicaloptions.com Laubach J, et al. ASCO 2017. Abstract 8002.

Elotuzumab + RVD in ND MM: Efficacy N = 40 pts evaluable for response Received study therapy, ≥ 1 follow- up assessment Median time to first response ≥ PR: 25 days (95% CI: 22-29) Median DoR: NR Response After 4 Cycles, % All Pts (N = 40) Pts With ASCT (n = 20) Pts Deferring ASCT ORR 82 95 70 PR 28 25 30 VGPR 40 45 35 CR 15 5 Response, n (%) All Pts (N = 40) Pts Completing 4 Cycles (n = 34) After 4 Cycles Best Response ORR (≥ PR) 33 (82) 34 (85) 33 (97) VGPR (≥ VGPR) 22 (55) 28 (70) 22 (65) 29 (88) CR + sCR 6 (15) 14 (35) 14 (41) ASCT, autologous stem cell transplantation; DoR, duration of response; MM, multiple myeloma; ND, newly diagnosed; NR, not reached; RVD, lenalidomide/bortezomib/dexamethasone; sCR, stringent CR. Slide credit: clinicaloptions.com Laubach J, et al. ASCO 2017. Abstract 8002.

Elotuzumab + RVD in ND MM: All-Grade AEs Occurring in > 20% of Pts AE, n (%) Pts (N = 40) Fatigue 24 (60) Neuropathy 22 (55) Musculoskeletal/joint pain Infection 20 (50) Back/neck pain 19 (48) Diarrhea 18 (45) Edema 15 (38) Constipation Cough 14 (35) Mood alteration Rash Insomnia 12 (30) AE, n (%) Pts (N = 40) Nausea 10 (25) Hyperglycemia Thrombocytopenia 9 (23) Hypophosphatemia Paresthesia Dyspnea AE, adverse event; ND, newly diagnosed; MM, multiple myeloma; RVD, lenalidomide/bortezomib/dexamethasone. Slide credit: clinicaloptions.com Laubach J, et al. ASCO 2017. Abstract 8002.

Elotuzumab + RVD in ND MM: Grade ≥ 3 AEs Hematologic AE, % Pts (N = 40) Grade 3 Grade 4 Grade 5 Thrombocytopenia 10 5 Anemia Febrile neutropenia Lymphopenia 2 Neutropenia Nonhematologic AE, % Pts (N = 40) Grade 3 Grade 4 Grade 5 Hypophosphatemia 12 Back pain 10 Fatigue Lung infection Hypertension 8 Syncope Increased ALT 5 Fever Hyperglycemia 2 Hypotension Rash Sepsis Cardiac arrest Respiratory failure 7 pts discontinued treatment All no immediate ASCT 2 pts died (sepsis, 1 on study, 1 > 30 days after discontinuation of treatment) AE, adverse event; ALT, alanine aminotransferase; ASCT, autologous stem cell transplantation; MM, multiple myeloma; ND, newly diagnosed; RVD, lenalidomide/bortezomib/dexamethasone. Slide credit: clinicaloptions.com Laubach J, et al. ASCO 2017. Abstract 8002.

Elotuzumab + RVD in ND MM: Conclusions Quadruple therapy with elotuzumab + RVD associated with high level of overall response in newly diagnosed pts with MM However, AEs led to discontinuation in 15% (6/40) of pts within 4 cycles of treatment 50% of pts had infection, including grade ≥ 3 lung infection (n = 4), grade 4 (n = 1) and 5 (n = 1) sepsis Investigators concluded that high ORR among pts receiving ≥ 4 cycles of elotuzumab + RVD is promising, but may require schedule changes or dose reductions to improve toxicity, clinical benefit AE, adverse event; MM, multiple myeloma; ND, newly diagnosed; RVD, lenalidomide/bortezomib/dexamethasone. Slide credit: clinicaloptions.com Laubach J, et al. ASCO 2017. Abstract 8002.

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