1. Phase III EMN02/HO95 MM Trial: Upfront ASCT Prolongs PFS vs Bortezomib, Melphalan, Prednisone in Newly Diagnosed MM
CCO Independent Conference Coverage* of the 2016 ASCO Annual Meeting, June 3-7, 2016
*CCO is an independent medical education company that provides state-of-the-art medical information to healthcare professionals through conference coverage and other educational programs.
ASCT, autologous stem cell transplantation; MM, multiple myeloma; PFS, progression-free survival.
This activity is supported by educational grants from Amgen, Ariad, Bayer Healthcare Pharmaceuticals, Celgene Corporation, Genentech, Incyte, Merck, and Taiho Pharmaceuticals.

2. Phase III EMN02/HO95 MM Trial: Upfront ASCT in Newly Diagnosed MM
Use of combination regimens has improved CR rates, PFS, and OS in previously untreated pts with MM[1-3]
In the era of effective novel agents, the role of high-dose melphalan with ASCT as SoC in newly diagnosed MM uncertain[1]
EMN02/HO95 MM: prospective, randomized phase III trial evaluating upfront ASCT vs bortezomib/melphalan/prednisone for newly diagnosed MM[4]
Comparisons included: upfront ASCT vs novel agent-based therapies; single vs double ASCT; consolidation vs no consolidation therapy; safety and toxicity; quality of life
Results include prespecified interim analysis (33% of required events observed)
ASCT, autologous stem cell transplantation; MM, multiple myeloma; SoC, standard of care.
1. Cavo M, et al. Blood. 2011;117: Moreau P, et al. Blood. 2015;125: Bianchi G, et al. Blood. 2015;126: Cavo M, et al. ASCO Abstract 8000.
Slide credit: clinicaloptions.com

3. EMN02/HO95 MM Trial: Study Design
1:1 (centers with single ASCT policy)
1:1:1 (centers with double ASCT policy)
Stratified by ISS I vs II vs III
VMP x 4, 42-day cycles:
V: 1.3 mg/m2 Days 1, 4, 8, 11, 22, 25, 29, 32
M: 9 mg/m2 Days 1-4
P: 60 mg/m2 Days 1-4
(n = 497)
Induction: VCD* x day cycles
CTX 2-4 g/m2 +
G-CSF
PBSC collection
VRD† x 2,
28-day cycles
consolidation therapy
Adult pts yrs with symptomatic, newly diagnosed MM
(N = 1192)
Randomization 1
Randomization 2
Lenalidomide
10 mg daily
Days 1-21/28
No consolidation therapy
HDM x 1-2 courses:
M: 100 mg/m2 +
Single (n = 488) or
double (n = 207) ASCT
(n = 695)
ASCT, autologous stem cell transplantation; CTX, cyclophosphamide; G-CSF, granulocyte-colony stimulating factor; HDM, high-dose melphalan; ISS, International Staging System; M, melphalan; MM, multiple myeloma; P, prednisone; PBSC, peripheral blood stem cell; QoL, quality of life; R, randomization; VCD, bortezomib/cyclophosphamide/dexamethasone; V, bortezomib; VMP, bortezomib/melphalan/prednisone; VRD, bortezomib/lenalidomide/dexamethasone.
*Bortezomib 1.3 mg/m2 twice weekly, cyclophosphamide 500 mg/m2 Days 1-8, dexamethasone 40 mg day of and day after bortezomib.
†Bortezomib 1.3 mg/m2 twice weekly, lenalidomide 25 mg Days 1-21, dexamethasone 20 mg Days 1, 2, 4, 5, 8, 9, 11, 12.
Primary endpoint: PFS from R1 and R2
Secondary endpoints: response, OS from R1 and R2, toxicity, QoL
Slide credit: clinicaloptions.com
Cavo M, et al. ASCO Abstract 8000.

4. EMN02/HO95 MM Trial: Pt Population
Characteristic
VMP (n = 497)
ASCT (n = 695)
Median age, yrs (IQR)
58 (52-63)
58 (53-62)
Male,% 56 59
ISS stage/revised ISS stage, % I II
III
41/19
38/64
21/17
41/16
39/67
20/17
FISH analysis, %*
Standard risk
High risk
54.9
45.1
49.8
50.2
ASCT, autologous stem cell transplantation; IQR, interquartile range; ISS, International Staging System; MM, multiple myeloma; VMP, bortezomib/melphalan/prednisone.
*Evaluable pts: VMP, n = 401; ASCT, n = 582.
Slide credit: clinicaloptions.com
Cavo M, et al. ASCO Abstract 8000.

5. EMN02/HO95 MM Trial: Pt Baseline Laboratory Assessment
Value, Median (IQR)*
VMP (n = 497)
ASCT (n = 695)
Albumin (g/L)
3.8 ( )
3.8 ( )
BM plasma cells, % (IQR)
50 (30-70)
60 (30-80)
Β2-microglobulin (mg/L)
3.3 ( )
3.3 ( )
Calcium (mmol/L)
2.35 ( )
2.34 ( )
Creatinine (mg/dL)
0.92 ( )
0.89 ( )
Hemoglobin (g/dL)
11.0 ( )
11.0 ( )
LDH > upper limit, %
22.7
24.5
Platelets (x 109/L)
231 ( )
223 ( )
ASCT, autologous stem cell transplantation; BM, bone marrow; IQR, interquartile range; ISS, International Staging System; LDH, lactose dehydrogenase; MM, multiple myeloma; VMP, bortezomib/melphalan/prednisone.
*Unless otherwise noted.
Slide credit: clinicaloptions.com
Cavo M, et al. ASCO Abstract 8000.

6. EMN02/HO95 MM Trial: Efficacy
Outcome
VMP
ASCT
HR (95% CI;
P Value)
PFS
Overall population, n
Median, mos
3 yr, %
497 44
57.5
695 NR
66.1
0.73 ( ; .003)
Standard-risk cytogenetics, n
220 46
69.6
290
76.6
0.68 ( ;
.034)
High-risk cytogenetics, n
181 32
43.2
292 42
55.2
0.69 ( ;
.010)
Response
(n = 451)
(n = 641) --
VGPR or better, %
73.8
85.5
< .001
ASCT, autologous stem cell transplantation; MM, multiple myeloma; NR, not reached; VGPR, very good partial response; VMP, bortezomib/melphalan/prednisone.
Median follow-up: 26 mos (range: mos)
Slide credit: clinicaloptions.com
Cavo M, et al. ASCO Abstract 8000.

7. EMN02/HO95 MM Trial: Safety
AE, %
VMP (n = 472)
ASCT (n = 627)
Grade 2-4
Grade ≥ 3
Anemia
10.0
0.6
55.5
15.8
Neutropenia
41.7
29.0
79.4
78.2
Thrombocytopenia
29.7
15.3
84.2
82.1
Gastrointestinal
19.1
5.7
34.0
12.0
Mucositis
0.2 --
33.0
15.6
Febrile neutropenia
23.8
17.5
Sepsis
4.3
3.2
Respiratory infections
7.6
1.7
4.9
2.6
Peripheral neuropathy
36.4
13.8
7.3
1.6
Fatigue
12.1
1.5
7.5
1.3
Cardiac
5.3
2.0
6.1
1.8
AE, adverse event; ASCT, autologous stem cell transplantation; MM, multiple myeloma; VMP, bortezomib/melphalan/prednisone.
Slide credit: clinicaloptions.com
Cavo M, et al. ASCO Abstract 8000.

8. EMN02/HO95 MM Trial: Conclusions
Upfront ASCT significantly prolonged PFS vs VMP in pts with newly diagnosed MM
Benefit seen in overall population and in high- and low- risk cytogenetic subgroups
Upfront ASCT significantly improved response (VGPR or better) vs VMP
In the era of novel agent-based therapy, upfront HDM and ASCT remains a standard of care for younger, fit pts with newly diagnosed MM
ASCT, autologous stem cell transplantation; HDM, high-dose melphalan; MM, multiple myeloma; VGPR, very good PR; VMP, bortezomib/melphalan/prednisone.
Slide credit: clinicaloptions.com
Cavo M, et al. ASCO Abstract 8000.

9. Go Online for More CCO Coverage of ASCO 2016!
Short slideset summaries of all the key data
Additional CME-certified analyses with expert faculty commentary on all the key studies in:
Breast, genitourinary, and lung cancers
Hematologic malignancies
Immunotherapy
clinicaloptions.com/oncology