1. What we know about myeloma in elderly patients from trials and observational studies?
Heinz Ludwig
Department of Medicine I
Center for Oncology, Hematology and Palliative Care
Wilhelminenhospital, Vienna, Austria

2. Goals of therapy in elderly patients
Rapid symptom control
Optimal quality of life
Few and acceptable side effects
Best possible quality of response
Long PFS
Long OS
Cure ?

3. Drug combinations for elderly patients
Possible options
1-drug*
2 - drugs
3- drugs
4 - drugs
Dex
Bendamustine+P
MPT
VMPT
Thal VD
VMP
MP*
CTD
Thal-Dex
VTD
L-ldDex
*only exceptional cases
Most commonly used combinations contain 2-3 drugs

4. The variation in biological fitness in a specific age cohort increases
Characteristics of the Elderly Patient Chronological age does not necessarily correlate with biological age
All three individuals are 70 years old
Fit Minor morbidity significant morbidity
The variation in biological fitness in a specific age cohort increases
with rising age, but the ‚biology‘ of myeloma cells does not vary with age

5. further dose reduction
Treatment of patients with multiple myeloma not eligible for transplantation
Assess fraility
Fit
Unfit
Frail
Full go
Slow go
Very slow go
2 or 3 drug regimen
reduce dose
2 (3) drug regimen
further dose reduction
MP, CTX-P
VD, Ld

6. Instruments for assessing fraility and allocation to treatment groups
Fit
Unfit
Frail
Age <80 yr
Fit >80 yr
Unfit >80 yr
ADL 6
IADL 8
Charlson 0
ADL 5
IADL 6-7
Charlson 1
ADL ≤4
IADL ≤5
Charlson ≥2
Go-go
Moderate-go
Slow-go
Full-dose regimens
Dose level 0
Reduced-dose regimens
Dose level -1
Reduced-dose
Palliative approach
Dose level -2
Assess
Age
ADL
IADL
Charlson
comorbidity
score
Palumbo A et al. IMW 2013

7. Adaptation of dose according to risk factors
Agent
Dose level 0
Dose level-1
Dose level - 2
Dexamethasone
40 mg
20 mg
10 mg
Melphalan
0.25 mg/kg or 9 mg/m2
0.18 mg/kg or 7.5 mg/m2
0.13 mg/kg or 5 mg/m2
Thalidomide
100 mg
50 mg
50 mg/qod
Lenalidomide
25 mg
15 mg
Bortezomib
1.3 mg twice weekly, sc
1.3 mg weekly, sc
1.0 mg weekly, sc
Prednisone
60 mg/m2
30 mg/m2
15 mg/m2
Cyclophosphamide
Palumbo et al.,BLOOD 2011

8. Comorbidities relevant for treatment selection in myeloma
Polyneuropathy
Avoid bortezomib (or use once weekly sc)
Renal impairment
Consider dose adaptations when using lenalidomide
Bone marrow insufficiency
Careful dosing of cytoreductive drugs, consider single agent dexamethasone
Cardiac arrhythmias/
dysfunction
Cave: Thalidomide & high dose dexamethasone
Immune system
Careful dosing of cytoreductive drugs
Diabetes
Cave: high dose dexamethasone
Cognitive function/
compliance
Consider iv regimens

9. Higher risk of mortality in patients ≥ 75 years of age
Retrospective meta-analysis of 4 EU phase III trials (N = 1,435) with MP, MPT, VMP, and VMPT
Median follow up 33 months
Median OS in total population 50 months
Estimated 3-year OS 68% in patients < 75 years of age vs 57% in patients ≥ 75 years of age (HR 1.44, CI , p < 0.001)
HR (95% CI)
p value
All
1.44 (1.20–0.72)
< 0.001 MP
1.21 (0.90–1.64)
0.21
MPT
1.12 (0.81–1.56)
0.49
VMP
1.62 (1.04–2.52)
0.03
VTP/VMPT
3.02 (1.86–4.90)
0.1 1 10
Higher mortality in patients < 75 years of age
Higher mortality in patients ≥ 75 years of age
Bringhen S, et al. Haematologica. 2013;98:980-7.

10. Age and Organ Damage Correlate with Poor OS: Meta-analysis of 4 Randomized Trials
n=1435 (≥ 65 yrs ): MPT vs MP, VMP vs MP, VMP vs VMPT-VT
Bringhen et al. Haematologica 2013;98(6):

11. *Meta-analysis of the 6 trials:  PFS () OS
Phase III studies incorporating novel agents in the non-transplant setting
New Regimen
Comparator
Outcome
MPT (6 Trials)*
vs. MP
MPT  PFS 5/6,  OS 2/6
CTDa
CTDa ORR
VMP
VMP  PFS,   OS
VMPT  VT
  PFS.   OS
VMP  VT or VP
VDT  VT or VP ns
MPR R
MPR
or MP
  PFS LD Ld
Ld  PFS,   OS
LD continous
Ld x 18, vs MPT x 12
Ld cont PFS,   OS
*Meta-analysis of the 6 trials:  PFS () OS

12. HR=0.67 in favor of MPT, p<0.0001
MPT vs MP: Meta-analysis of 1685 individual-patient data of 6 randomized trials
0.0
0.2
0.4
0.6
0.8
1.0
Survival proportion 12 24 36 48
months MP
MPT
Median 14.9 mos
( )
Median 20.3 mos
( )
HR=0.67 in favor of MPT, p<0.0001
PFS OS
0.0
0.2
0.4
0.6
0.8
1.0 12 24 36 48
months
Median 32.7 mos
( )
Median 39.3 mos
( )
HR=0.83 in favor of MPT, p=0.005*
MPT MP
*Cox model for treatment, with analysis stratified by study using a random effects (frailty) model
Fayers et al. Blood 2011, accepted for publication 30 May 2011

13. MPT: Pros and Cons Pros Cons Survival benefit Thalidomide toxicity
Oral regimen
Not expensive
Cons
Thalidomide toxicity
Suboptimal in cytogenetic high risk group
Shorter survival after relapse

14. MP vs. VMP (VISTA) Final updated OS analysis
Median follow-up 60.1 months
31% reduced risk of death
100 90 80 70 60 50 40 30 20 10
Median OS benefit: 13.3 months
5-year OS rates: 46.0% vs 34.4%
Patients alive (%)
Group N Event Median HR (95% CI) P-value M
VMP (0.567, 0.852)
Time (months)
San Miguel et al. JCO 2013

15. Overall survival in different subgroups: VMP vs. MP
San Miguel et al., JCO 2013

16. VMP induced CR is associated with improved outcome
Time to progression
Time to next therapy
Treatment-free interval
Overall survival
Harousseau JL et al., BLOOD 2010

17. VD vs. VTD vs. VMP followed by bortezomib maintenance therapy
Para-meter VD
VTD
VMP
>VGPR
36%
44%
40%
ORR
68%
78%
71%
PNP G3-4
15%
26%
20%
PFS (mos)
13.8
18.4
17.3
Niesvitzky R. et al., BLOO,

18. Global QoL during VD, VTD and VMP
induction therapy
VD vs. VTD or VMP: shorter PFS, similar OS, better tolerance
Niesvizky R et al., ASH 2011

19. 14/04/2017
Treatment schedule
Median age 71 y; 30% >75 y; Median KPS 80%; 63% IgG; 33% B2M > % albumin < 35 g/L 19

20. PFS and OS: VMP vs VMPT –VT
Progression free survival Overall survival
landmark analysis
Palumbo A et al. ASH 2012

21. Overall survival, Landmark analysis

22. Overall survival from relapse
Palumbo et al. ASH 2012 (Abstract 200)

23. VMPT-VT versus VMP in newly diagnosed elderly patients
Significant OS benefit in patients
< 75 years of age (none in pts > 75 years)
With stage ISS 1-2 (tendency for  OS in stage ISS 3)
With CR (none in pts with VGPR/PR)
Benefit in ‚good risk‘ patients with CR only
Grade 3- 4 adverse events during VT maintenance
PN 7%
Hematological toxicity 5%
Infection 3%
Discontinuation due to AEs 12%
Palumbo et al. ASH 2012 (Abstract 200), oral presentation

24. How to reduce toxicity of Bortezomib and and maintain efficacy?
Bortezomib once weekly
longer duration of therapy
similar cumulative dose
similar efficacy
less toxicty (G3/4 neurotoxicity)
Bortezomib subcutaneously
10 times lower serum peak concentration
similar area under the curve
less neurotoxicity

25. - MPR-R vs. MPR vs. MP (MM015 trial) RANDOMIZATION •
Stratified by age (<75 years vs > 75 years) and stage (ISS I/II vs III)
ISS, International Staging System; MP,
melphalan
, prednisone; MPR,
, prednisone,
lenalidomide
; MPR R,
with
maintenance; PBO, placebo. MP M:
0.18 mg/kg, days 1 4 P:
2 mg/kg, days 1
PBO:
days 1 21
MPR R:
10 mg/day po
, days 1
Placebo R
RANDOMIZATION
Double-blind Treatment Phase
Disease
Progression
Maintenance
Lenalidomide
(25 mg/day) +/
Dexamethasone
Open
Label
Extension Phase
Cycles (28
day) 1 9
Cycles 10+
N = 459, 82 centers in Europe, Australia, and Israel
MPR-R vs. MPR vs. MP (MM015 trial)
Phase 3 randomized, double-blind, placebo-controlled study designed to evaluate the safety and efficacy of continuous lenalidomide treatment (melphalan, prednisone, and lenalidomide induction followed by lenalidomide maintenance [MPR-R]) vs fixed-duration regimens of melphalan and prednisone (MP) or melphalan, prednisone, and lenalidomide (MPR)
459 patients were recruited at 82 centers in Europe, Australia, and Israel between February 2007 and September 2008
Approximately 50% of patients had stage III disease, and the median age was 71 years (MPR-R and MPR arms) and 72 years (MP arm)
Patients were randomly assigned to receive MP (n = 154), MPR (n = 153), or MPR-R (n = 152)
Patients could elect to receive open-label lenalidomide (25 mg/day) ± dexamethasone following disease progression
The primary analysis was MPR-R versus MP and the primary endpoint was progression-free survival (PFS)
The study was not powered to compare MPR-R vs MPR
Following a pre-planned interim analysis at 50% information, an independent data-monitoring committee confirmed the superiority of MPR-R over MP at extending PFS
The cutoff for these data was April 15, 2009, allowing for a median follow-up of 9.4 months for PFS
A second pre-planned interim analysis at 70% information was conducted for data on December 1, 2009, allowing for a median follow-up period of 21 months for PFS
Reference
Palumbo A, Delforge M, Catalano J, et al. A phase III study to determine the efficacy and safety of lenalidomide combined with melphalan and prednisone in patients ≥ 65 years with newly diagnosed multiple myeloma (NDMM): continuous use of lenalidomide vs fixed-duration regimen. Blood. 2010;116: [abstract 622].

26. Progression-free and overall survival
HR, hazard ratio; MP,
melphalan
, prednisone; MPR,
, prednisone,
lenalidomide
; MPR - R,
with
maintenance; OS, overall survival; PFS, progression
free survival; TTP, time to progression.
Progression
Free and Overall Survival
All Patients •
TTP HR advantages were similar: MPR
R vs MP = 0.337; MPR vs MP = 0.826
Time (Months)
Patients (%)
HR 0.395 P
< .001
HR 0.796
= .135 10 20 30 40 25 50 75
100
Median PFS
MPR R
31 months
14 months MP
13 months 60 4
year OS
59%
58%
HR 0.898
P =
.579
HR 1.089
= .648
Progression-free and overall survival

27. PFS and OS with MPR-R and MPR patients aged 65-75 years

28. FIRST: Phase 3 trial of Lenalidomide + low-dose Dex vs MPT (IFM 07-01; MM-020)
Centres in EU, Switzerland, APAC, USA, and Canada
RANDOMIZATION
Rd (28-day cycle; until disease progression)
Lenalidomide 25 mg/day, days 1–21 Dexamethasone* 40 mg/day, days 1, 8, 15, and 22
Inclusion criteria
N = 1,623
Previously untreated MM
Age  65 years or not eligible for a transplant
No neuropathy of grade > 2
Rd (28-day cycle; up to 18 cycles)
Lenalidomide 25 mg/day, days 1–21 Dexamethasone* 40 mg/day, days 1, 8, 15, and 22
MPT (6-week cycle; up to 12 cycles )
Melphalan* 0.25 mg/kg/day, days 1–4 Prednisone 2.0 mg/kg/day, days 1–4 Thalidomide* 200 mg/day
Primary end-point: PFS
*In patients aged > 75 years: Dex 20 mg/day, melphalan 0.20 mg/kg/day, thalidomide 100 mg/day
NCT Available from: 28 28 28

29. What is the optimal duration of first line therapy?
Trials & duration of therapy (months)
VMP (Vista) 12
MPT trials
6-18.5
CTDa
6-9
MPR-R
9, R untill PD
VMPT-VT
12.5, VT maintenance: 2 years
LD (MM20)
Continously until PD/intolerance
Duration of therapy: minimally 6, maximally 12 months
Most experts recommend ≈ 9 months

30. Outcome with novel combinations
CR rate (%)
Median PFS (months)
Median OS (months)
MP1,2
rare
11–20
BP2 -
14* 32
MPT3 10
20.3 39
CTDa4 13 33
VMP5 30
21.7–27.4
56.4
MPR-R6 31
59% (4-yr OS)
VMP-VT/VP7 42 35
58% (5-yr OS)
VMPT-VT8,9
35.3
59.3% (5-yr OS)
LD continuous10
≥PR 75% vs. 62%
28% ↓ risk for PD
22% ↓ risk for death
1MTCG. J Clin Oncol 1998;16(12):
2Ludwig et al., BLOOD 2009
2Pönisch et al. J Cancer Res Clin Oncol. 2006;132:
3Fayers et al. Blood 2011; 118(5):
4Morgan et al. Blood 2011;118:1231-8
5San Miguel et al. JCO 2013; 31(4):
6Palumbo et al. N Engl J Med 2012;366(19):
7Mateos et al. Blood 2012; 120:
8Palumbo et al. ASH 2012 (Abstract 200), oral presentation
9Palumbo et al. ASH 2011 (Abstract 653), oral presentation
10Facon et al. ASH 2013 (Abstract 2), oral presentation

31. Hematologic CR correlates with long PFS and OS in elderly patients treated with novel agents
Retrospective analysis: 3 randomized European trials of GIMEMA and HOVON groups (N=1175)
First-line treatment
MP (n=332), MPT (n=332), VMP (n=257), VMPT-VT (n=254)
Significant benefit also seen when analysis is restricted to patients >75 years old
PFS OS CR CR
VGPR
Probability
VGPR
Probability PR PR
P<0.001
P<0.001
Gay et al. Blood 2011; 117(11):

32. Immunophenotypc CR correlates with OS GEM2005 >65y
100
PFS
Immunophenotypic CR 90% at 3y
“Stringent CR” 38% at 3y
Conventional CR 57% at 3y
PR (≥70% reduction) 28% at 3y 80 60 40 20
Paiva et al; J Clin Oncol. 2011;29(12):

33. Cytogenetic abnormalities are a major prognostic factor in elderly patients with MM: IFM experience
1,890 patients (median age 72, range 66–94), including 1,095 patients
with updated data on treatment modalities and survival
OS according to t(4:14)
OS according to del(17p)
0.50
1.00
0.75
0.25
0.00
0.50
1.00
0.75
0.25
0.00
p < 10.4
p < 10.6
Probability of OS
Probability of OS
t(4:14) neg
t(4:14) pos
del(17p) < 60
del(17p) ≥ 60 1 2 3 4 5 1 2 3 4 5
Time (years)
Time (years)
Whatever the treatment, t(4;14) and del(17p) were associated with shorter PFS and OS; similar results were achieved in the subgroup of 335 patients > 75 years
1. Avet-Loiseau H, et al. J Clin Oncol (22): Hulin et al. Blood 2012:[abstract 204].

34. The challenge of high-risk CA [t(4;14), del(17p), t(14;16)] in NDMM elderly patients
Study
No of pts with high-risk CA
Outcome of high-risk CA patients
MPT/MP1 NR
CTDa/MP1
(MRC Myeloma IX)
CTDa does not overcome the effect of high-risk CA and is not significantly better than MP in high-risk CA
RD/Rd2 (E4A03) 21
2y OS=76% for high-risk CA vs 91%
VMP/MP3 (VISTA) 46
Absence of OS benefit, median OS 44.1mo. VMP vs 50.6 mo., MP
VMP/VTP – VT/VP4
(GEM-05) 44
Adverse prognosis of both t(4;14) and del (17p) regardless of induction and maintenance. Median OS t(4;14)=29 mo., del(17p) = 27mo.
First generation novel agents only partly overcome the negative prognosis
of high-risk CA in newly diagnosed elderly patients with MM
1. Bergsagel PL, et al. Blood. 2013;121: Rajkumar SV, et al. Lancet Oncol. 2010;11: San Miguel J, et al. J Clin Oncol. 2013;31: Mateos MV, et al. Blood. 2011;118:

35. Maintenance studies - summary
Thalidomide
 PFS
no improvement in OS
 Reduced OS after relapse
Negative impact on high risk pts
Clinical practice
recommendations
50 mg for ≈ 12 mos may be considered
Lenalidomide
increased risk for SPM
Bortezomib-thalidomide
Tendency for  PFS and  OS but not significant superior over VP

36. Summary: Treatment results in elderly patients
MPT,  PFS, +/- OS, can be toxic in elderly pts
VMP,  PFS  OS, may induce severe PNP
Ld,  PFS,  OS, low dose Dex recommended
Thal-Dex, an option for fit pts
CTDa vs MP,  overall response rate,  CR, VGPR
Bendamustine-Pred, approved for first line TX
Thalidomide maintenance  PFS, but not OS
MPR with Lenalidomide maintenance PFS, but not OS
VT maintenance  not significantly better than VP

37. The natural course of multiple myeloma
Maintenance

38. Treatment of relapsed/refractory MM General considerations
Components of initial therapy
Alkylating-based
Dexamethasone-based
IMiD-based
Bortezomib-based
Efficacy of initial therapy
Quality of response
Tolerance of tretament
Duration of respose
Patient status and type of relapse
Age, performance status, glucose metabolism
Aggressive vs non-aggressive relapse
Bone marrow reserve
Renal function impairment
Pre-existing peripheral neuropathy
Oral vs. iv therapy
IMiD, immunomodulatory derivative; MM, multiple myeloma

39. IMiD based frontline TX
Treatment of Relapsed/Refractory Myeloma
Frontline Therapy successful?
Yes No
Long duration of response Select other TX (Class switch)
Yes No
Repeat first line TX Select other TX
Bortezomib based frontline TX:
IMiD based frontline TX
Pomalidomide
IMiD-based TD
MPT
CTD Rd
(MPR)
Old Type MP
DCEP
M-100 +
ASCT
Bort-based VD
VMP
VTD
Ludwig et al.
The Oncologist
2011

40. Retreatment with bortezomib: a meta-analysis including 23 studies
23 trials, 1051 patients
Patients refractory or not refractory to bortezomib
11 studies including bortezomib-refractory pts
6 studies excluding bortezomib-refractory pts
6 studies missing information on bortezomib-refractory pts
Combinations
Bortezomib ± Dex: 4 studies
Bortezomib + combination therapy: 19 studies
Knopf et al. IMW 2013 (Abstract P-228), poster presentation

41. Results of meta-analysis of retreatement with bortezomib in different risk groups
Variable
ORR
TTP (months)
OS (months)
Relapsed
57%
8.5
19.7
Relapsed/>refractory
19%
5.9
20.4
≤ 4 prior TX lines
43%
8.2
13.3
> 4 prior TX lines
29%
7.1
20.0
Boz + Dex
51%
7.9
19.2
Combination
36%
16.2
Pooled analysis
8.4
Knopf et al., IMW 2013

42. Carfilzomib a second generation proteasome inhibitor

43. Single agent Carfilzomib in relapsed/refractory patients
Progressive disease at enrollment, Relapsed from 2 prior TX lines, Must include bortezomib
Must include thalidomide or lenalidomide, Refractory to last line
Response category
All patients
(n=267)
High risk cytogenetics
(n=71) CR
0.4%
VGPR
5.1%
4.2% PR
18.3%
25.4% MR
13.2%
ORR
37%
29.5%
PFS(median)
3.7 mos
3.6 mos
DOR (median)
7.8 mos
6.9 mos
Siegel D et al., BLOOD 2012

44. Pomalidomide + LoDex vs HiDex (MM-003): Phase III Trial Design
Stratified by age (≤ 75 vs > 75 yrs), number of previous treatments (2 vs > 2), disease population (refractory vs relapsed/refractory vs intolerant/refractory)
28-day cycles
POM + LoDex Pomalidomide 4 mg on Days Dexamethasone 40 mg (if ≤ 75 yrs) or 20 mg (if > 75 yrs) on Days 1, 8, 15, 22 (n = 302)
Follow-up for OS and SPM until 5 yrs Post enrollment
Until PD*
Patients with relapsed/refractory myeloma (N = 455)
DOR, duration of response; DVT, deep venous thrombosis; LoDex, low-dose dexamethasone; HiDex, high-dose dexamethasone; ORR, overall response rate; OS, overall survival; PD, progressive disease; PFS, progression-free survival; POM, pomalidomide; SPM, second primary malignancies.
HiDex Dexamethasone 40 mg (if ≤ 75 yrs) or 20 mg (if > 75 yrs) on Days 1-4, 9-12, (n = 153)
Companion trial MM-003C: Pomalidomide 21/28 days
Until PD*
Primary endpoint: PFS
Secondary endpoints: OS, ORR, DOR, safety
*Independently adjudicated in real time.
Thromboprophylaxis indicated for patients receiving pomalidomide or with history of DVT.
San Miguel JF, et al. ASCO Abstract 8510.

45. Pomalidomide + LoDex vs HiDex: Key Criteria for Pts With Relapsed/Refractory MM
All patients
Refractory to last therapy
≥ 2 previous therapies
≥ 2 consecutive cycles of lenalidomide and bortezomib (alone or in combination) or adequate previous alkylator therapy
Failed bortezomib and lenalidomide
Progression within 60 days; PR with progression within 6 mos, and/or bortezomib intolerant after ≥ 2 cycles and achieving ≤ MR
Refractory or relapsed/refractory
Primary refractory (never achieved better than PD to any therapy) or relapsed and refractory (relapsed after having ≥ SD for ≥ 2 cycles of therapy to ≥ 1 previous regimen and then developed PD ≤ 60 days of completing their last treatment)
LoDex, low-dose dexamethasone; HiDex, high-dose dexamethasone; MR, molecular response; PD, progressive disease; PR, partial response, SD, stable disease.
San Miguel JF, et al. ASCO Abstract 8510.

46. Pomalidomide + LoDex vs HiDex (MM-003)
PFS (ITT Population)
OS (ITT Population)
Mos
Mos
San Miguel JF, et al. ASCO Abstract 8510.

47. Pomalidomide + LoDex vs HiDex Adverse Events (MM-003)
AE, %
POM + LoDex
(n = 300)
HiDex
(n = 150)
Grade 3/4 hematologic AEs
Neutropenia 48 16
Anemia 33 37
Thrombocytopenia 22 26
Grade 3/4 nonhematologic AEs
Infections 30 24
Pneumonia 13 8
Bone pain 7 5
Fatigue 6
Asthenia 4
Grade 3/4 AEs of interest
DVT/PE 1
Peripheral neuropathy*
Discontinuation due to AEs 9 10
AEs, adverse events; DVT, deep vein thrombosis; HiDex, high-dose dexamethasone; LoDex, low-dose dexamethasone; OS, overall survival; PE, pulmonary embolism; PFS, progression-free survival; POM, pomalidomide.
*Includes hyperesthesia, peripheral sensory neuropathy, paraesthesia, hypoesthesia, and polyneuropathy.
San Miguel JF, et al. ASCO Abstract 8510.

48. Zoledronic Acid vs Clodronate in Newly Diagnosed MM: SREs
Significantly reduced incidence of SREs* with zoledronic acid vs clodronate
Regardless of presence of bone lesions at baseline
HR: 0.74 (P = .0004) 40
CLO
35.3% 30
27.0%
Patients With an SRE (%)
ZOL 20 10
HR, hazard ratio; SRE, skeletal-related event 6 12 18 24 30 36 42
Time From Randomization (Mos)
Patients at Risk, n
ZOL
981
663
506
390
284
201
138 97
CLO
979
629
465
337
256
173
112 74
*SREs defined as vertebral fractures, other fractures, spinal cord compression, and the requirement for radiation or surgery to bone lesions or the appearance of new osteolytic bone lesions.
Morgan GJ, et al. ASH Abstract 311. 48

49. Planned and/or ongoing studies
VD vs VTD vs VMP + V maintenance (UPFRONT study)
VRd vs Rd + Rd maintenance (SWOG S0777)
Rd vs MPT vs Rd + Rd maintenance (MM20/IM(FIRST trial)
Rd vs MPR vs CRP + maintenance R vs RP (EMNTG)
MPT+T vs MPR+R (HOVON 87-NMSG 18, ECOG EA1A06)
CTDa vs RCD +/- R maintenance (MRC Myeloma XI)
VP vs VMP vs VCP + VP maintenance (EMNTG)
Carfilzomib + MP (CARMYSAP trial): ORR of 92% (40% VGPR). EHA 2012
MLN9708 plus LD and MLN9708 plus MP: EHA 2012
Rd vs MEL140 (DSMM XIII)
Pomalidomide + Dex vs Dexamethasone: MM 005
Alternating treatment with different regimens: VMP and RD (PETHEMA/GEM) Bortezomib + Bendamustine + Prednisone (PETHEMA/GEM)

50. New drugs in clinical evaluation
Agent
Mechanism of action
Panobinostat, Vorinostat, Givinostat, Romidepsin
HDAC inhibitor
Perifosine, GSK
Akt inhibitor
Temsirolismus, Everolismus
mTOR inhibitor
Selumetinib
MEK/ERK inhibitor
Plitidepsin (aplidin)
Jun N-terminal Kinase (JNK) activator, anti-angiogenic activity
Dinaciclib
CDK inhibitor
MLN8237
Aurora kinase inhibitor
ARRY-520
Kinesin spindle protein (KSP) inhibitor
Elotuzumab
anti-CS1
Daratumumab
anti-CD38
BHQ880
anti-DKK1
BT062
anti-CD138
Tabalumab
Anti-B cell activiating factor (BAFF)
BI-505
Anti-intercellular adhesion molecule 1 (ICAM-1)

51. Recommendations for clinical practice
Assess
comorbidities
degree of functional impairment
Select most appropriate drug regimen
Adapt dose if required
Consider the increased risk of infections within first weeks/months of therapy
Optimize supportive care
Antibiotics, antivirals, growth factors, anti-thrombotics

52. Thank you for your attention
The future looks bright for elderly
myeloma patients
Thank you for your attention