1. 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.

2. 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: Lonial S, et al. N Engl J Med. 2015;373: Elotuzumab [package insert] Durie BG, et al. Lancet. 2017;389: Usmani SZ, et al. Blood Cancer J. 2015;5:e Laubach J, et al. ASCO Abstract 8002.
Slide credit: clinicaloptions.com

3. 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 Abstract 8002.

4. 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 Abstract 8002.

5. 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 Abstract 8002.

6. 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 Abstract 8002.

7. 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 Abstract 8002.

8. 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 Abstract 8002.

9. 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 Abstract 8002.

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