1. Relapsed and Refractory Myeloma
Ruben Niesvizky Myeloma Center Myelomacenter.org

2. Multiple Myeloma: Natural History of Disease
Asymptomatic
Symptomatic
Relapsing
Refractory
M-Protein Level
Remission duration decreases with each line of therapy
Active Myeloma
Relapse
Remission
MGUS or Indolent Myeloma // //
Second- or Third-Line Therapy
Frontline Therapy
Durie B; International Myeloma Foundation.
Concise review of the disease and treatment options: multiple myeloma. 2011/2012 edition;
Kumar SK, et al. Mayo Clin Proc. 2004;79:

3. Outline Approach to the patient with RRMM: Proteasome inhibitors
Evidence based
Factors to be considered in selecting therapy
Proteasome inhibitors
Inmunomodulatory Agents
HDAC inhibitors
Alkylating agents

4. Clinical Considerations for Relapsed/Refractory Disease
Disease characteristics/prior therapy
Line of therapy
Plateau phase=quiescent period
Aggressiveness of relapse
Relapsed or relapsed and refractory disease
“High risk disease”
Prior therapies (eg SCT, prior IMiD, bortezomib-based therapy)

5. Clinical Considerations for Relapsed/Refractory Disease
Disease characteristics/prior therapy
Line of therapy
Plateau phase=quiescent period
Aggressiveness of relapse
Relapsed or relapsed and refractory disease
“High risk disease”
Prior therapies (eg SCT, prior IMiD, bortezomib-based therapy)

6. Response Duration Decreases With Successive Therapies
578 patients; median age 65 years (follow up 55 months)
Overall survival
One year 72%
Two years 55%
Three years 22%
84% died within five years
Kumar SK, et al. Mayo Clin Proc. 2004;79:

7. APEX: Bortezomib Early or Late Relapse
1 prior therapy
n = 132
> 1 prior therapy
n = 200
Median TTP (months)
7.0
4.9
CR (%)
10%*
7%†
CR + PR (%)
51%*
37%†
Median Duration of Response (months)
8.1
7.8
1-year Survival
89%
73%
* Evaluable patients, response to bortezomib after 1 prior therapy: n = 128
† Evaluable patients, response to bortezomib after >1 prior therapy: n = 187
Sonneveld P, et al. Haematologica. 2005;90: Abstract P ; Data on file; Millennium Pharmaceuticals, Inc.

8. Improved Outcomes with the Early Use of LenDex : TTP and OS
Time to Progression Overall Survival
2nd Line (LenDex)
Median 17.1 months
≥ 3th line(LenDex)
Median 10.6 months
2nd Line (LenDex)
Median 42 months
≥ 3th line(LenDex)
Median 35.8 month
Stadmauer EA et al. Eur J Haematol 2009; 82:426-32

9. Clinical Considerations for Relapsed/Refractory Disease
Disease characteristics/prior therapy
Line of therapy
Plateau phase=quiescent period
Aggressiveness of relapse
Relapsed or relapsed and refractory disease
“High risk disease”
Prior therapies (eg SCT, prior IMiD, bortezomib-based therapy)

10. Time to Progression After SCT Correlates With OS After Initial Relapse
Kumar SK, et al. Bone Marrow Transplant. 2008;42:

11. Clinical Considerations for Relapsed/Refractory Disease
Disease characteristics/prior therapy
Line of therapy
Plateau phase=quiescent period
Aggressiveness of relapse
Relapsed or relapsed and refractory disease
“High risk disease”
Prior therapies (eg SCT, prior IMiD, bortezomib-based therapy)

12. Frontline vs Relapsed Refractory
Treatment Naive
Response to Therapy Survival Outcomes
High risk features Genomic instability
Relapsed and Refractory
Response to Therapy
Survival Outcomes
Toxicities and Co-morbidities
Toxicities and Co-morbidities

13. Outcomes in Relapsed and Refractory Multiple Myeloma
Frontline
Treatment
Relapsed
Relapsed /Refractory
Expected
survival (months)
20-50
Sensitivity to
therapy
Sensitive
Treatment limitations/
comorbidities
Peripheral neuropathy (~15% at diagnosis)
14-16
Less Sensitive/Resistant
>80% incidence of peripheral neuropathy Compromised marrow reserve
Cytopenia
6-10
Resistant
Intolerant to or
ineligible for available therapy
Elderly population ( risk for heart, lung, renal, liver dysfunction, diabetes)
Adapted from: Durie BGM. Multiple Myeloma. International Myeloma Foundation. 2011/2012 edition.
Jagannath S. Clin Lymphoma Myeloma. 2008;8 Suppl 4:S149-S156.
For Training and Educational Purposes Only. Not for Distribution.

14. Nature of Relapse How did the patient present?
80% share clinical features with presentation
Has been a shift on presentation?
Intact immunoglobulin to light chain only
Non-secretory relapse
Extra medullar disease

16. Nature of Relapse How did the patient present?
80% share clinical features with presentation
35% relapse both light chain and intact Ig
49.6% intact Ig
10% free light chain only

17. Survival according to paraprotein and FLC secretion at first relapse.
Brioli A et al. Blood 2014;123:
©2014 by American Society of Hematology

18. Survival from relapse according to paraprotein and FLC secretion at relapse for patients with IgG and IgA paraproteins.
Brioli A et al. Blood 2014;123:
©2014 by American Society of Hematology

19. Nature of Relapse How did the patient present?
80% share clinical features with presentation
35% relapse both light chain and intact Ig
49.6% intact Ig
10% free light chain only
Has been a shift on presentation?
Intact immunoglobulin to light chain only
Non-secretory relapse
Extra medullar disease

21. Progression-free survival according to the presence of extramedullary (EM) involvement at diagnosis.
Varettoni M et al. Ann Oncol 2009;21:
© The Author Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please

22. Outcome according to baseline PET/CT.
Zamagni E et al. Blood 2011;118:
©2011 by American Society of Hematology

23. Patient Heterogeneity

24. Clinical Considerations for Relapsed/Refractory Disease
Toxicity considerations
Peripheral neuropathy
Thrombotic risk
Myelosuppression
Impact of prior therapies (eg, SCT, other cumulative toxicity)

25. Overall survival in 6-year intervals from time of diagnosis
ANY PROGRESS?
Overall survival in 6-year intervals from time of diagnosis
Time (months)
Proportion of patients
0.2
0.4
0.6
0.8
1.0 20 40 60 80
100
120
140
2001–2006
1995–2000
1989–1994
1983–1988
1977–1982
1971–1976
Kumar et al. Blood. 2008
Brenner et al. Blood. 2008 25 25

27. < 65 años
> 65 años
Kumar et al: Leukemia Nov 2013

28. Proteosome Inhibitors
Bortezomib
Carflizomib
Ixazomib
Oprozomib

29. Proteasome Inhibitors
Outcomes Correlate with Depth of Response

30. Quality of Response: Survival
Niesvizky et al., Br J Haematol Oct;143(1):46-53

31. Proteasome Inhibitors
Benefits of Retreatment

32. Bortezomib Retreatment – A Retrospective Multicenter Survey
Retrospectively collected data- multicenter non-interventional survey of pts who received bortezomib for a second time (retreatment)
Patients: 65 pts,19 centers; median age 65 yrs
Treatment received
Median 4 prior therapies
Retreatment
Initial
bortezomib
Diagnosis
52 mos
Mean of 5 cycles
Mean of 4 cycles
6 pts received additional therapy
Median
Bortezomib mg/m2
Initial
Re-treatment
1.3
94%
86%
1.0 2%
12%
other 8% 4%
+ Dex
39%
61%
Results: 49 evaluable (modified ITT)
Retreatment
Best Response
Treatment Outcomes
Safety: AE occurring in > 2 patients
% Patients
months
Patients (n)
Hrusovsky I, et al. ASH 2007, abstract #2720

33. Petrucci et al, Br J Haem 2013,160,649-659

34. Petrucci et al, Br J Haem 2013,160,649-659

35. Proteasome Inhibitors
Carflilzomib

36. Study 003-A1: Open-Label Phase 2b Study of Single-Agent Carfilzomib in Relapsed and Refractory Multiple Myeloma (R/R MM)
Study Population (N=266)
Relapsed from ≥2 prior lines of therapy
Must include bortezomib
Must include thalidomide or lenalidomide
Refractory to last regimen
Carfilzomib IV on days 1, 2, 8, 9, 15 and 16 every 28 days
20 mg/m2 in Cycle 1
and 27 mg/m2 from Cycle 2 and beyond
(maximum 12 cycles)
Primary endpoint: ORR
IMWG response criteria (IRC assessed)
Secondary endpoints
CBR (ORR+ MR), DOR, OS, PFS, TTP, safety
CBR = clinical benefit rate; DOR = duration of response; IMWG = International Myeloma Working Group; IRC = Independent Review Committee; MR = minimal response; ORR = overall response rate; OS = overall survival; PFS = progression-free survival
Siegel D, et al. Blood. 2012;120:

37. Single-Agent Carfilzomib: Response Rates
TTR: 1.9 mo (≥PR) and 1.0 mo (≥MR)
DOR: 7.8 mo (≥PR) and 8.3 mo (≥MR)
N = 257 response-evaluable population
DCR = 69%
Percentage of Patients
CBR = 37%
ORR = 24%
Subset analyses of higher risk populations showed similar response rates (e.g., unfavorable cytogenetics, baseline peripheral neuropathy)
CR = complete response; PD = progressive disease; PR = partial response; SD = stable disease; TTR = time to response; VGPR = very good partial response
Siegel D, et al. Blood. 2012;120:
*IRC-determined; 11 patients had unconfirmed response

38. Single-Agent Carfilzomib: PFS, OS
1.0
0.8
0.6
0.4
0.2
0.0 3 9 12 18 6 15 3 12 21 27
1.0
0.8
0.6
0.4
0.2
0.0 15 6 9 18 24
Median OS = 15.6 mo
(95% CI 13.0–19.2)
Median PFS = 3.7 mo (95% CI 2.8–4.6)
Proportion alive and without progression
Proportion surviving
Months
N = 257 response-evaluable population
Months
Siegel D, et al. Blood. 2012;120: 38

40. Phase II Trial of Carfilzomib Plus Len/Dex in R/R MM (1-3 prior lines of therapy)
Carfilzomib 20/27 mg/m2 IV*
*20 mg/m2 cycle 1 days 1 and 2 only, 27 mg/m2 thereafter
D1/D2
D8/D9
D15/D16
Week 1
Week 2
Week 3
Week 4: rest
Lenalidomide d1-d21 25 mg/d PO D1 D8
D15
D22
Dexamethasone 40 mg/d PO
Response (N = 52 pts receiving maximal planned dose)
n (%)
ORR
Stringent CR CR
VGPR PR SD
40 (77)
2 (4)
1 (2)
19 (37)
18 (35)
3 (6)
Median duration of response, mos (range)
22.1 ( )
Wang M, et al. Blood. 2013;122: 40 40

41. For ASH Dec 09
Phase III ASPIRE Trial: Carfilzomib + Len/Dex vs Len/Dex in R/R MM (ongoing)
Press release-
PFS 26.3 vs 17.6 HR 0.69:
CRd
Carfilzomib
27 mg/m2 IV day 1, 2, 8, 9, 15, and 16 (20 mg/m2 on days 1, 2 of cycle 1 only)
Lenalidomide
25 mg Days 1-21
Dexamethasone
40 mg once weekly
Study Population (N=780)
Measurable disease
1-3 prior regimens
Relapse or PD
Response to ≥1 prior regimen
Exclusion factors:
Bortezomib-refractory
Len/dex-refractory
Prior carfilzomib Rd
Lenalidomide
25 mg Days 1-21
Dexamethasone
40 mg once weekly
Stratify: Prior bortezomib, prior lenalidomide, β2 microglobulin level
Primary endpoint: PFS
28-day cycles
Available at: Accessed April 29, 2014.
DRAFT 41

42. Phase 1b Study of High-Dose Carfilzomib + Dexamethasone in R/R MM
Endpoint
CFZ
20/45
20/56
Total
ORR, % 57 50 55
CR, %
VGPR, % 14 25
PR, % 43 30
DOR NR
PFS, months
5.4
6.0
Study population: N=22
(expanded 007 cohort)
Median prior regimens: 4
Regimen: (28-day cycles)
Carfilzomib 20/45 or 20/56 mg/m2 30-min IV D1,2,8,9,15,16
Dexamethasone 20 mg
D1,2,8,9,15,16 then 40 mg D22
Efficacy
Treatment-emergent Grade ≥3 AE, %
CFZ
20/45
20/56
Total
Hematologic
Thrombocytopenia
Anemia
Lymphopenia 29 14 50 25 36 27 18
Nonhematologic
Hypertension
Hypophosphatemia
Pneumonia 7 13 9
Safety
CFZ = carfilzomib
Badros A, et al. ASH Abstract 4036.

43. Phase III ENDEAVOR: Carfilzomib + Dex vs Bortezomib/Dex in R/R MM1
Note use of higher carfilzomib dose—based on results from 004 trial, which suggested dose-response relationship of carfilzomib2 Cd
Carfilzomib
20/56 mg/m2 IV D1,2, 8, 9, 15, 16
Dexamethasone
20 mg PO or IV D1, 2, 8, 9, 15, 16, 22, 23
28-day cycle
Study Population (N=888)
Measurable disease
Responsive to at least 1 prior therapy
Relapsed following 1-3 prior treatment regimens
ECOG PS 0-2 Vd
Bortezomib
1.3 mg/m2 IV or SC D1, 4, 8, & 11
Dexamethasone
20 mg PO or IV D1, 2, 4, 5, 8, 9, 11, 12
21-day cycle
Stratify: Prior PI, prior lines of therapy, ISS, bortezomib IV vs. SC
Primary endpoint: PFS
Treat until PD or unacceptable toxicity
ClinicalTrials.gov. Available at: Accessed March 26, 2014.
Vij R, et al. Blood. 2012;119:

44. Novel PIs Under Investigation in R/R MM
Agent
Status
Ixazomib
Two phase I studies showed activity of single-agent ixazomib[2,3]
Oprozomib
Phase 1 dose-escalation study showed some activity in patients with heavily pretreated hematologic malignancies, including MM[4]
Richardson PG, et al. ASH Abstract 302.
Lonial S, et al. ASCO Abstract 8017.
Kumar S, et al. ASCO Abstract 8514.
Savona MR, et al. ASH Abstract 203.

45. Ixazomib: Oral Proteasome Inhibitor

46. Ixazomib treatment duration and response.
Kumar S K et al. Blood 2014;124:
©2014 by American Society of Hematology

47. Proteasome Inhibitors
Oprozomib

52. OPomDex Study Design (Phase 1b)

53. Proteosome Inhibitors
Bortezomib
Carflizomib
Ixazomib
Oprozomib
Immunomodulating Agents Ub
Substrates +
Thalidomide
Lenalidomide
Pomalidomide

54. Immunomodulating Agents

55. Pomalidomide in Relapsed/Refractory Multiple Myeloma
POM + LoDEX achieved responses in pts with prior LEN and/or BORT treatment, including those who are refractory1-4
Study
Phase N
Treatment
Population
Median Prior Tx (Range)
≥ PR
Lacy4 2 60
POM: 2 mg
(28/28-day cycle)
Dex: 40 mg/week
1-3 prior Tx, relapsed/refractory
2 (1-3)
65% 34
LEN-refractory
4 (1-14)
32% 35
DEX: 40 mg/week
LEN- and BORT- refractory
6 (3-9)
26%
POM: 4 mg
1-3 prior Tx, LEN-refractory
37%
6 (2-11)
29%
1. Lacy MQ et al. J Clin Oncol. 2009;27: Lacy MQ et al. Leukemia. 2010;24:1934.
3. Lacy MQ et al. Blood. 2011;118: Lacy MQ et al. Blood. 2011;118: Abstract 3963. 55

56. Median No. Prior Regimens Refractory to Recent Therapy (%)
Pomalidomide
Pts, n
Median No. Prior Regimens
Refractory to Recent Therapy (%)
ORR (%)
Pomalidomide ± dex1
191 5
100
2534
Pomalidomide, dex2 70 6 NR
2629
Pomalidomide, dex3 84 85
3435
Pomalidomide, cyclophosphamide, prednisone4 32
(1 to 3)
44* 59
Pomalidomide, dex, clarithromycin5 46
NR (at least 3) 60
*Len specifically
1. Vij R et al. J Clin Oncol. 2012;30. Abstract 8016.
2. Lacy MQ et al. Blood. 2011;118: Leleu X et al. Blood. 2011;118. Abstract 812.
4. Palumbo A et al. Blood. 2011;118. Abstract 632.
Mark TM et al. Blood. 2011;118. Abstract 635.

57. ClaPd: Study Design Day
A single-center, phase 2 study of Clarithromycin combined with Pomalidomide + Low Dose Dexamethasone in RRMM
Day
Dex
40mg PO
Pomalidomide 4 mg PO
Clarithromycin 500mg PO BID
p.o., orally; b.i.d., twice a day; RRMM, relapsed, refractory MM.

58. Clarithromycin???

59. Results Best Response (IMWG Criteria) n (%) Overall (N = 98)
ORR (≥ PR)
56 (57)
CBR (≥ MR)
65 (66)
sCR
6 (6)
VGPR
17 (17) PR
33 (34) MR
9 (9) SD
23 (23) PD
10 (10)
98 patients completed at least 1 cycle of ClaPD.
median number of cycles received was 6 (range 1–25)
median study follow-up was months (range 1.0–25.6)
In responding patients, median time to PR was 1 cycle (range 1–7).
Median time to best response was 2 cycles (range 1-14).
IMWG, International Myeloma Working Group; CBR, clinical benefit rate; MR, minimal response; PD, progressive disease; sCR, stringent complete response; SD, stable disease.

60. Treatment History With Len/Bort Did Not Influence Response to ClaPD
Best Response (IMWG Criteria)
n (%)
Overall
(N = 98)
Lenalidomide
refractory
(N = 83)
Bortezomib
Refractory
(N = 82)
Lenalidomide and
bortezomib refractory
(N = 72)
ORR (≥ PR)
56 (57)
47 (63)
46 (56)
39 (54)
CBR (≥ MR)
65 (66)
56 (67)
54 (65)
(65)
sCR
6 (6)
6 (7)
5 (6)
5 (7)
VGPR
17 (17)
13 (16)
9 (13) PR
33 (34)
28 (34)
25 (35) MR
9 (9)
8 (10)
8 (11) SD
23 (23)
18 (22)
19 (23)
16 (22) PD
10 (10)
8 (12)
9 (11)
IMWG, International Myeloma Working Group; MR, minimal response; PD, progressive disease; sCR, stringent complete response; SD, stable disease.

61. OS by double-refractory state
Results
OS by cytogenetic risk
OS by double-refractory state
1.00
1.00
0.75
0.75
Survival (%)
0.50
Survival (%)
0.50
Standard risk
High risk
Not double-refractory
Double-refractory
0.25
0.25
Time (days)
Time (days)
Number of patients at risk Relapsed
Refractory
Number of patients at risk Relapsed
Refractory
Adverse cytogenetics did not appear to influence risk of death as of last study follow-up.
HR 1.05, 95%CI (0.49,2.26), P = 0.888
A history of being double-refractory, however, approached a significant effect on survival time.
HR 2.67, 95%CI (0.93,7.69), P = 0.068

62. IFM 2010-02: Study design End-points Primary: TTP
RRMM
Exposed to Len
del 17p and/or t(4;14)
Measurable disease
ECOG 0–2
PNn > 1 x109/L
Plat ≥ 75 x109/L
Hb ≥ 8 g/dL
CrCl ≥30 mL/min
Pomalidomide 4 mg/day, po, days 1–21 (of 28 d cycle)
Dexamethasone 40 mg, po, days 1, 8, 15, 22
Aspirin/LMWH once daily, continuously
Until progression
Safety analysis by DMC after 15 patients recruited
End-points
Primary: TTP
Secondary: Safety, Response rate (CBR), DoR, OS, PFS, EFS, cytogenetic groups
Median follow-up: 8.2 months
At data cut-off, 36 patients (72%) had discontinued trial
n (%)
Progression
25 (69)
Death other cause
1 (3)
Toxicity
9 (25)
Sponsor decision

63. IFM 2010-02: Time To Progression (ITT)
del17p
t(4;14)
ITT
O/N
Median
95% CI
ITT population
33 / 50
2.9
[2.7;5.0]
8-month TTP, % 22
del17p
12 / 22*
7.3
[2.7;14.7] 41
t(4;14)
24 / 32*
2.8
[1.9;4.0]
12.4

64. IFM 2010-02: Overall Survival
O/N
Median
95% CI
ITT population
26 / 50 12
[4.9;15.5]
8-month OS, % 55
del17p
12 / 22*
[2.4;-] 58
t(4;14)
16 / 32*
9.2
[4.6;-] 50

65. 40 mg weekly (20 mg after cycle 4)
Phase I/II: Carfilzomib/Pomalidomide/LoDEX (Car-Pom-d) in R/R MM
28-day cycles
(cycles 1-6)
Maintenance
(cycles 7+)
Study Population (N=79)
Relapsed and/or refractory measurable MM
Lenalidomide-refractory
Carfilzomib*
20/27 mg/m2 (D1-2, 8-9, 15-16)
Pomalidomide*
4 mg (D1-21)
Dexamethasone*
40 mg weekly (20 mg after cycle 4)
Carfilzomib
D1-2, 15-16
Pomalidomide
unchanged
Dexamethasone
Treatment continued until PD or unacceptable toxicity
All patients received antiviral treatment and aspirin 81 mg or low molecular weight heparin
*Dosing based on MTD established in phase 1
Primary endpoint: ORR
Secondary endpoints:
DOR, TTP, PFS, time to next therapy, OS
Shah JJ, et al. Blood. 2013;122:690.

66. Car-POM-d in R/R MM: Efficacy
Cytogenetic Risk (by mSMART)
Response, %
High (n = 18)
Intermediate (n = 19)
Standard (n = 38)
All Pts (N = 79)
ORR 78 53 74 70
VGPR 22 26 32 27 PR 56 42 43
Median PFS: 9.7 mos; median DOR: 17.7 months; median OS not reached
No significant difference in PFS or OS based on cytogenetics
80% of pts with del(17p) were alive at 12 mos; 58% were progression-free
Shah JJ, et al. Blood. 2013;122:690.

67. Proteosome Inhibitors
Bortezomib
Carflizomib
Ixazomib
Oprozomib
Immunomodulating Agents Ub
Substrates +
Thalidomide
Lenalidomide
Pomalidomide
HDAC inhibitors
Romidepsin
Vorinostat
Panobinostat

69. Phase 2 trial of the histone deacetylase inhibitor romidepsin for the treatment of refractory multiple myeloma
Niesvizky et al, Cancer Volume 117, Issue 2, pages , 22 SEP 2010

70. HDAC Inhibitors in RRMM
Description
Regimen N
ORR (> PR), %
HDAC Inhibitors
Romidepsin + bortezomib + dex[4] 25 60
Vorinostat + bortezomib[5]
143 17
Bortezomib + panobinostat + dex[6] 55
34.5

71. Vorinostat Bortezomib vs Placebo Bortezomib
Vorinostat: Median PFS: 7·63 months (95% CI 6·87-8·40)
Placebo: Median 6·83 months (5·67-7·73)
(hazard ratio [HR] 0·77, 95% CI 0·64-0·94;p=0·0100).
Dimopoulos et al,
Lancet Oncol Oct;14(11):

72. PANORAMA 1: Phase III Trial of Panobinostat + Bortezomib + Dex
Dexamethasone
Study Population (N=768)
Relapse or relapsed/refractory MM
Bortezomib-refractory excluded
1-3 prior lines of therapy
Stratification based on prior lines of therapy, prior bortezomib
Placebo
Bortezomib
Dexamethasone
Primary endpoint: PFS
Richardson PG, et al. ASCO Abstract 8510.

73. PANORAMA 1: Primary Endpoint Met (PFS)

74. Bortezomib Carflizomib Ixazomib Oprozomib Thalidomide Lenalidomide
Melphalan
Cyclophosphamide
Bendamustin Ub
Substrates +
Thalidomide
Lenalidomide
Pomalidomide
Romidepsin
Vorinostat
Panobinostat

75. Autotransplant for Refractory MM
SWOG Trial 8993
PFS OS
N = 66
Median = 11 mo
N = 66
Median = 19 mo
Vesole DH, et al. J Clin Oncol. 1999;17:

76. PBSCT in Relapsed MM TTP median HD Mel 19 months [95% CI 16—25]
PAD
Weekly CTX 400 mg/m2 x 21
HD Mel
Induction
Consolidation
TTP median
HD Mel 19 months [95% CI 16—25]
Cyclophosphamide 11 months [9—12];
hazard ratio 0·36 [95% CI 0·25—0·53];
p<0·0001).
Cook G et al,The Lancet Oncology, Volume 15, Issue 8, Pages , July 2014

77. A Phase 1 Study of Bendamustine and Melphalan Conditioning for Autologous Stem Cell Transplant with Multiple Myeloma.

78. Dose Levels for Bendamustine
On Day 1 Melphalan (100mg/m2)
On Day 2 Melphalan (100mg/m2) 1
30 mg/m2 2
60 mg/m2 3
90 mg/m2 4 5 6
125 mg/m2
100 mg/m2

79. Elotuzumab Daratumumab SAR650984 Bortezomib Carflizomib Ixazomib
Oprozomib
Melphalan
Cyclophosphamide
Bendamustine Ub
Substrates +
Filanesib
Palbociclib
Thalidomide
Lenalidomide
Pomalidomide
Romidepsin
Vorinostat
Panobinostat

81. The Team and Collaborators
Myelomacenter.org
Tomer Mark MD
Morton Coleman, MD
Roger Pearse, MD
Adriana Rossi, MD
David Jayabalan
Karen Pekle RNP
Arthur Perry PA
Susan Matthew, PhD
Scott Ely, MD/MPH
Selina Chen-Kiang, PhD
Monica Guzman, PhD
Giorgio Inghirami, MD
Linda Tegnestam RN
Kathleen Pogonowski RN
Stanley Goldsmith MD
Maureen Lane PhD
Paul Christos