1. How Newly Approved Agents Can Improve the Management of Relapsed/Refractory MM
Sagar Lonial, MD Professor and Chair
Hematology and Medical Oncology
Chief Medical Officer Winship Cancer Institute Emory University Atlanta, Georgia
This activity is supported by educational grants from Amgen; Celgene Corporation; Janssen Biotech, Inc., administered by Janssen Scientific Affairs, LLC; and Takeda Oncology.

2. About These Slides
Please feel free to use, update, and share some or all of these slides in your noncommercial presentations to colleagues or patients
When using our slides, please retain the source attribution:
These slides may not be published, posted online, or used in commercial presentations without permission. Please contact for details
Slide credit: clinicaloptions.com
Disclaimer: The materials published on the Clinical Care Options Web site reflect the views of the authors of the CCO material, not those of Clinical Care Options, LLC, the CME providers, or the companies providing educational grants. The materials may discuss uses and dosages for therapeutic products that have not been approved by the United States Food and Drug Administration. A qualified healthcare professional should be consulted before using any therapeutic product discussed. Readers should verify all information and data before treating patients or using any therapies described in these materials.

3. Faculty Sagar Lonial, MD Professor and Chair
Department of Hematology and Medical Oncology
Chief Medical Officer Winship Cancer Institute
Emory University Atlanta, Georgia
Sagar Lonial, MD, has disclosed that he has received consulting fees from Bristol-Myers Squibb, Celgene, Janssen, Merck, Millennium, Novartis, and Onyx and funds for research support from Bristol-Myers Squibb, Celgene, Janssen, Millennium, and Novartis.
This slide lists the faculty who were involved in the production of these slides.

4. Novel Myeloma Therapy Development
Novel Therapies
Novel Therapies
and Immunotherapy
Backbone
Atezolizumab Investigational
Lenalidomide
Carfilzomib
Daratumumab
Nivolumab Investigational
Thalidomide
Elotuzumab
Pomalidomide
Liposomal Doxorubicin
CAR T Investigational
Vaccines Investigational
Ixazomib
Bortezomib
Panobinostat
Isatuximab Investigational
Imid, immunomodulatory drug; HDAC, histone deacetylase; KSP, kinesin spindle protein, SINE, selective inhibitor of nuclear export
2003
2006
2007
2012
2013
2015
2016+
IMID
Chemotherapy
Monoclonal antibody
Vaccines
Proteasome inhibitor
HDAC inhibitor
Adoptive T cell therapy
Checkpoint inhibitors
Slide credit: clinicaloptions.com

5. Therapeutic Agents in Myeloma: Old vs New
“Older” novel agents
Bortezomib
Lenalidomide
Carfilzomib
Pomalidomide
“Newer” novel agents
Ixazomib
Elotuzumab
Earlier lines or induction therapy, partner for newer agents
Panobinostat
Daratumumab
Slide credit: clinicaloptions.com

6. Pt Case
A 65-yr-old pt presents with anemia and bone pain and was diagnosed with ISS stage I MM
Hemoglobin of 9.6 g/dL, normal WBC and platelets, total protein of 9.9 g/dL, normal creatinine and calcium levels
Skeletal survey shows diffuse lytic disease
SPEP/UPEP shows 4.2 g/dL of IgG kappa, and 210 mg/24 hrs of kappa light chains in the urine; FLC ratio is 5:1
He started on RVD x 4 cycles followed by ASCT and lenalidomide maintenance; he achieved CR at Day +100
He does well for 4 yrs but develops asymptomatic biochemical relapse over 12 mos with a protein of 1.2, mild anemia and questionable new bone lesion
ASCT, autologous stem cell transplantation; FLC, free light chain; ISS, International Staging System; MM, multiple myeloma; RVD, bortezomib/lenalidomide/dexamethasone; WBC, white blood cell.

7. Online Treatment Decision Aid for MM
Developed by 5 MM experts based on key factors they considered important to guide therapy
Enter specific pt characteristics using drop down menus
MM, multiple myeloma.

8. Pt Case: Expert Recommendations
Treatment recommendations from 5 MM experts for our pt scenario are shown
Available at: clinicaloptions.com/MyelomaTool

9. TOURMALINE-MM1: All Oral Regimen of Ixazomib With Rd in R/R MM
Randomized, double-blind, placebo-controlled phase III trial[1]
Primary endpoint: PFS by IRC per IMWG criteria[2]
Secondary endpoints (data not yet mature): OS, OS in del(17p) pts
Stratified by prior therapy (1 vs 2-3), ISS stage (I-II vs III), and prior PI exposure (yes vs no)
Ixazomib 4 mg PO Days 1, 8, 15 +
Lenalidomide 25 mg* Days
Dexamethasone 40 mg Days 1, 8, 15, 22
(n = 360)
R/R MM pts with measurable disease;
1-3 prior treatments;
CrCl ≥ 30 mL/min;
not refractory to PIs or lenalidomide
(N = 722)
28-day cycles
until PD or unacceptable toxicity
Placebo Days 1, 8, 15 +
Lenalidomide 25 mg* Days
Dexamethasone 40 mg Days 1, 8, 15, 22
(n = 362)
CrCl, creatinine clearance; Dex, dexamethasone; IMWG, International Myeloma Working Group; IRC, independent review committee; ISS, International Staging System; Len, lenalidomide; MM, multiple myeloma; PD, progressive disease; PI, proteasome inhibitor; Rd, lenalidomide/dexamethasone; R/R, relapsed/refractory.
*10 mg for pts with CrCl ≤ 60 or ≤ 50 mL/min.
Slide credit: clinicaloptions.com
Moreau P, et al. N Engl J Med. 2016;374:

10. TOURMALINE-MM1: Final PFS Analysis
Addition of ixazomib to Rd resulted in 35% improvement in PFS vs Rd alone
PFS benefit with ixazomib seen in all prespecified subgroups, including cytogenetic high risk, PI and IMiD exposed
100
Median PFS, Mos
Ixazomib + Rd: 20.6
Placebo + Rd: 14.7 80 60
Probability of PFS (%) 40
IMiD, immunomodulatory drug; PI, proteasome inhibitor; Rd, lenalidomide/dexamethasone.
HR: (95% CI: ; Log-rank P = .012)
Number of events: Ixazomib + Rd 129; placebo + Rd 157 20 2 4 6 8 10 12 14 16 18 20 22 24
Mos From Randomization
Slide credit: clinicaloptions.com
Moreau P, et al. N Engl J Med. 2016;374:

11. TOURMALINE-MM1: Outcomes by Cytogenetic Risk Group
ORR, %
≥ VGPR, %
≥ CR, %
Median PFS, Mos
IRd
Placebo+ Rd HR
All patients
78.3*
71.5
48.1* 39
11.7*
6.6
20.6
14.7
0.742*
Standard risk 80 73 51 44 12 7
15.6
0.640*
High risk (all)
79* 60
45* 21
12* 2
21.4
9.7
0.543
High risk: del(17p)† 72 48 15
11*
0.596
High risk: t(4;14) alone 89 76 53 28 14 4
18.5
12.0
0.645
*P < .05 for comparison between regimens. †Alone or with t(4;14 or t(14;16).
IRd, ixazomib plus lenalidomide/dexamethasone; Rd, lenalidomide/dexamethasone; VGPR, very good PR.
Median OS could not be estimated
In the IRd arm, median PFS in high-risk pts was similar to that in the overall pt population and in pts with standard-risk cytogenetics
Slide credit: clinicaloptions.com
Moreau P, et al. ASH Abstract 727.

12. ASPIRE: Addition of Carfilzomib to Rd in Relapsed/Progressive Myeloma
Randomized, open-label phase III trial
Stratified by β2-microglobulin, prior bortezomib, and prior lenalidomide
Pts with relapsed or progressive MM,
1-3 prior treatments with ≥ PR in ≥ 1 prior regimen,
ECOG PS 0-2, and CrCl ≥ 50 mL/min
(N = 792)
Until PD or unacceptable toxicity
KRd Carfilzomib Days 1, 2, 8, 9, 15, 16 for cycles 1-12,
Days 1, 2, 15, 16 for cycles 13-18,
and discontinued after cycle 18 +
Lenalidomide Days Dexamethasone Days 1, 8, 15, 22
28-day cycle (n = 396)
Rd Lenalidomide Days Dexamethasone Days 1, 8, 15, 22
28-day cycle
(n = 396)
CrCl, creatinine clearance; ECOG, Eastern Cooperative Oncology Group; KRd, carfilzomib/lenalidomide/dexamethasone; MM, multiple myeloma; PD, progressive disease; PR, partial response; PS, performance status; Rd, lenalidomide/dexamethasone.
Carfilzomib: 20 mg/m2 Days 1, 2 of cycle 1; 27 mg/m2 thereafter. Lenalidomide: 25 mg. Dexamethasone: 40 mg.
Slide credit: clinicaloptions.com
Stewart AK, et al. N Engl J Med. 2015;372:

13. Mos Since Randomization
ASPIRE: PFS
Significant improvement in PFS in KRd arm vs Rd arm
100
KRd Rd
(n = 396) (n = 396)
Median PFS, mos
HR (95% CI) ( ) 80
P < .0001 60
PFS (%) 40 20
KRd, carfilzomib/lenalidomide/dexamethasone; Rd, lenalidomide/dexamethasone.
KRd Rd 6 12 18 24 30 36 42 48
Mos Since Randomization
Pts at Risk, n
KRd Rd
Slide credit: clinicaloptions.com
Stewart AK, et al. N Engl J Med. 2015;372:

14. ENDEAVOR: Kd vs Vd in Relapsed MM
Randomized, open-label, multicenter phase III trial
Primary endpoint: PFS
Secondary endpoints: OS, ORR, DoR, grade ≥ 2 peripheral neuropathy, safety
Stratified by prior PI therapy, prior lines of treatment, ISS stage, and route of V administration (IV vs SC)
Kd* (n = 464)
Relapsed MM with 1-3 prior lines of therapy; prior V or K if response occurred with no discontinuation due to toxicity (N = 929)
Until PD or unacceptable toxicity
Vd† (n = 465)
*Carfilzomib: cycle 1 only, 20 mg/m2 IV on Days 1, 2 followed by 56 mg/m2 on Days 8, 9, 15, 16, then 56 mg/m2 on Days 1, 2, 8, 9, 15, 16 of a 28-day cycles; dexamethasone: 20 mg on Days 1, 2, 8, 9, 15, 16, 22, 23 of a 28-day cycle. On days when carfilzomib is administered, dexamethasone given 30 mins to 4 hrs prior to carfilzomib.
†Bortezomib: 1.3 mg/m2 IV bolus or SC on Days 1, 4, 8, 11 of a 21-day cycle; dexamethasone: 20 mg on Days 1, 2, 4, 5, 8, 9, 11, 12 of a 21-day cycle.
Dex, dexamethasone; DoR, duration of response; K, carfilzomib; Kd, carfilzomib/dexamethasone; MM, multiple myeloma; PD, progressive disease; PI, proteasome inhibitor; V, bortezomib; Vd, bortezomib/dexamethasone.
Slide credit: clinicaloptions.com
Dimopoulos MA, et al. Lancet Oncol. 2016;17:27-38.

15. Mos Since Randomization
ENDEAVOR: PFS
Kd (n = 464)
171 (37) 18.7
Vd (n = 465)
243 (52) 9.4
100 80 60 40 20
Disease progression or death, n (%) Median PFS, mos HR for Kd vs Vd (95% CI)
0.53 (0.44–0.65) 1-sided P < .0001
PFS (%)
Kd, carfilzomib/dexamethasone; Vd, bortezomib/dexamethasone.
Kd Vd 6 12 18 24 30
Mos Since Randomization
Median follow-up: 11.2 mos
Slide credit: clinicaloptions.com
Dimopoulos MA, et al. Lancet Oncol. 2016;17:27-38.

16. ENDEAVOR: PFS by Prior Bortezomib
No Prior Bortezomib
Prior Bortezomib
100 80 60 40 20
100 80 60 40 20
PFS (%)
PFS (%)
Kd Vd
Kd Vd
Kd, carfilzomib/dexamethasone; NE, not estimable; Vd, bortezomib/dexamethasone.
Mos Since Randomization
Mos Since Randomization Kd
(n = 214) Vd
(n = 213)
1-Sided
P Value
(n=250)
(n=252)
Median PFS, mos NE
11.2
15.6
8.1
ORR, % (95% CI)
84 (78–88)
65 (59–72)
< .0001
71 (65–77)
60 (54–66)
.005
Slide credit: clinicaloptions.com
Dimopoulos MA, et al. Lancet Oncol. 2016;17:27-38.

17. Novel Agents for Frontline Multiple Myeloma: A New Era of Efficacy
Rationally Based Combination Therapies (HDAC and Proteasome Inhibitors)
Protein Ub
Protein aggregates
(toxic) Ub Ub Ub Ub
26S proteasome
HDAC6
Bortezomib, carfilzomib, ixazomib, oprozomib, salinosporamide A Ub
Panobinostat,
vorinostat, rocilinostat
HDAC6
dynein
HDAC, histone deacetylase. Ub
Lysosome
Aggresome
HDAC6 Ub Ub
Dynein
Microtubule
Autophagy
Hideshima T, et al. Clin Cancer Res. 2005;11: Catley L, et al. Blood. 2006;108:
Slide credit: clinicaloptions.com

18. Phase III PANORAMA-1 Trial: PFS, OS With Addition of Panobinostat to Vd
Primary endpoint reached: median PFS ↑ by 3.9 mos
Median OS ↑ by 4.5 mos: NS
OS[2]
PFS[1]
100 80 60 40 20
100 80 60 40 20
Pan + Vd
Placebo + Vd
Pan + Vd
Placebo + Vd
Probability of PFS (%)
Probability of OS (%) 4 8 12 16 20 24 28 32 36 8 16 24 32 40 48 56 64
Bort, bortezomib; dex, dexamethasone; NS, not significant; pan, panobinostat.
Mos
Mos
Median PFS, Mos (95% CI)
HR (95% CI)
Median OS, Mos (95% CI)
HR (95% CI)
P Value
Arm
P Value
Arm
Pan + Vd
Placebo + Vd
12.0 ( )
8.1 ( )
Pan + Vd
Placebo + Vd
40.3 ( )
35.8 ( )
0.63
( )
0.94
( )
< .0001
.5435
1. San-Miguel JF, et al. Lancet Oncol. 2014;15: San-Miguel JF, et al. ASH Abstract 3026.
Slide credit: clinicaloptions.com

19. In Absence of Biomarker, Other Predictors of Benefit: Prior Treatment
PANORAMA-1 subgroup analysis: pts with ≥ 2 previous treatments, including bortezomib and an IMiD
FDA approved indication based on subgroup analysis
100
Median PFS,
Mos (95% CI)
HR (95% CI) 80
Pan + Vd
Placebo + Vd
12.5 ( )
4.7 ( )
0.47
( ) 60
PFS Probability (%)
Bort, bortezomib; dex, dexamethasone; IMiD, immunomodulatory drug; pan, panobinostat. 40 20 2 4 6 8 10 12 14 16 18 20 22 24 26 28
Mos
Slide credit: clinicaloptions.com
Richardson PG, et al. Blood. 2016;127:

20. Are There Better Partners for Panobinostat?
Data with other proteasome inhibitors now available
Carfilzomib appears to have more synergy with less overlapping gastrointestinal toxicity
SC bortezomib remains an unknown variable
Ixazomib studies in progress
IMiD combinations not fully explored
IMiD, immunomodulatory drug.

21. Panobinostat/Carfilzomib: Response by Prior Treatment and Risk
Response, n (%)
All Pts (N = 42)
Dose Level 4 (n = 32)
Prior Bort (n = 37)
Bort Refractory (n = 15)
IMiD Refractory (n = 12)
Dual Refractory (n = 5)
High Risk* (n = 11)
Std Risk (n = 21)
ORR
28 (67)
23 (72)
26 (70)
10 (67)
9 (75)
4 (80)
8 (73)
15 (71)
CBR
33 (79)
28 (88)
31 (84)
13 (87)
11 (92)
5 (100)
9 (82)
16 (76)
≥ VGPR
14 (33)
12 (38)
13 (35)
3 (20)
5 (42)
1 (20)
5 (46)
8 (38) PR
11 (34)
7 (47)
4 (33)
3 (60)
3 (27)
7 (33) MR
5 (12)
5 (16)
5 (14)
2 (17)
1 (9)
1 (5) SD
7 (17)
2 (6)
2 (13)
1 (8)
4 (19) PD
2 (5)
1 (3)
Bort, bortezomib; CBR, clinical benefit rate; IMiD, immunomodulatory drug; MR, minimum response; PD, progressive disease; SD, stable disease; Std, standard.
*High risk: 1q amp, del(1p), t(4;14), t(14;16), del(17p), del(13q)
Slide credit: clinicaloptions.com
Berdeja JG, et al. Haematologica. 2015;100:

22. Targets for Monoclonal Antibodies in MM
Daratumumab Isatuximab MOR202
Lucatumumab Dacetuzumab
Lorvotuzumab
IL-6
Siltuximab
Elotuzumab
Ulocuplumab
BAFF
Tabalumab
CD38
CD40
CD56
SLAMF7
CXCR4
APRIL
BCMA
CD229
CD317
CD200
MM Cell
β2M
CD28
Approved agents
CD70
CD19
In clinical development
CD74
PD-1
CD138
ICAM-1
Preclinical activity
Potential targets
BI-505
Pembrolizumab Nivolumab Pidilizumab
Indatuximab Ravtansine
Milatuzumab
Slide credit: clinicaloptions.com
Lonial S. ASCO New Drugs in Oncology: Ixazomib, Elotuzumab,
and Daratumumab in Myeloma.

23. ELOQUENT-2: PFS With Addition of Elotuzumab to Rd
Elo + Rd Rd
HR: 0.73 (95% CI: ; P = .0014)
Median PFS, mos (95% CI)
19.4
( )
14.9
( )
100
1-Yr PFS 80
68%
2-Yr PFS 60
PFS (%)
3-Yr PFS
57%
41% 40
26%
Elo + Rd 20
27% Rd
18%
E, elotuzumab; Rd, lenalidomide/dexamethasone. 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48
PFS (Mos)
Pts at Risk, n
Elo + Rd Rd
321
325
259
215
227
181
195
157
171
130
144
106
125 80
107 67 94 60 85 51 59 36 34 15 19 7 8 3 3
PFS benefit with Elo + Rd maintained over time (vs Rd):
Overall 27% reduction in the risk of disease progression or death
Relative improvement in PFS of 44% at 3 yrs
Slide credit: clinicaloptions.com
Dimopoulos MA, et al. ASH Abstract 28.

24. ELOQUENT-2: Time to Next Treatment
Elo + Rd Rd
HR: 0.62 (95% CI: )
Median TTNT, mos (95% CI)
33 ( )
21 ( )
100 80 60
Next Treatment (%)
Pts Without
Elo + Rd 40 Rd 20
E, elotuzumab; Rd, lenalidomide/dexamethasone; TTNT, time to next treatment. 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48
Mos to Next Treatment
Pts at Risk, n
Elo + Rd Rd
321
325
315
305
294
276
282
251
259
232
239
206
225
193
208
174
198
166
182
148
174
135
165
120
153
105
144 96
138 89
126 85
118 76 94 46 65 30 46 20 32 13 14 5 6 3 3 1
Median delay of 1 yr in the time to next treatment for Elo + Rd vs Rd
Slide credit: clinicaloptions.com
Dimopoulos MA, et al. ASH Abstract 28.

25. ELOQUENT-2: PFS With del(17p) or t(4;14)
100
100 80 80 60 60
Elo + Rd
PFS (%)
PFS (%) 40 40 Rd
Elo + Rd
HR: 0.65
(95% CI: ) 20 20
HR: 0.53
(95% CI: ) Rd
E, elotuzumab; NE, not estimable; Rd, lenalidomide/dexamethasone. 4 8 12 16 20 24 28 32 36 4 8 12 16 20 24 28 32 36
PFS (Mos)
PFS (Mos)
Median PFS (95% CI)
Median PFS (95% CI)
Elo + Rd: (16.62-NE) Rd: ( )
Elo + Rd: ( ) Rd: ( )
Slide credit: clinicaloptions.com
Lonial S, et al. ASCO Abstract 8508.

26. ELOQUENT-2: PFS by Age Younger Than 65 Yrs 65 Yrs or Older 2-yr PFS
100
100
2-yr PFS
2-yr PFS 80 80 60 60
PFS (%)
PFS (%)
40%
42% 40
Elo + Rd 40
Elo + Rd Rd 20
E, elotuzumab; Rd, lenalidomide/dexamethasone.
30% 20
25% Rd
HR: (95% CI: )
HR: (95% CI: )
Mos
Mos
Slide credit: clinicaloptions.com
Lonial S, et al. ASCO Abstract 8508.

27. Pt Case
A 65-yr-old pt, diagnosed with ISS stage I MM, received RVD x 4 cycles followed by ASCT and lenalidomide maintenance
After 4 yrs, developed asymptomatic biochemical relapse over 12 mos with a protein of 1.2 g/dL, mild anemia, and questionable new bone lesion
Pt requested all-oral regimen and elected to begin treatment with ixazomib plus Rd
He does well for 24 mos and then has progression with anemia and bone pain
ASCT, autologous stem cell transplantation; ISS, International Staging System; MM, multiple myeloma; Rd, lenalidomide/dexamethasone; RVD, bortezomib/lenalidomide/dexamethasone.

28. Pt Case: Expert Recommendations

29. Daratumumab: Mechanism of Action
Anti-CD38 IgGκ monoclonal antibody
Direct and indirect antimyeloma activity[1-5]
Depletes CD38+ immunosuppressive regulatory cells[5]
Promotes T-cell expansion and activation[5]
Sanchez L, et al. J Hematol Oncol. 2016;30:51.
Lammerts van Bueren J, et al. ASH Abstract 3474.
Jansen JMH, et al. Blood. ASH Abstract 2974.
de Weers M, et al. J Immunol. 2011;186:
Overdijk MB, et al. MAbs. 2015;7:
Krejcik J, et al. Blood. 2016;[Epub ahead of print].
Slide credit: clinicaloptions.com

30. Phase II SIRIUS: Daratumumab Monotherapy in Refractory Myeloma
Change in Paraprotein From Baseline
–100
–90
–75
–50
–25 25 50 75
100 35
ORR: 29% 30 25
Maximum Change From Baseline (%) 20
ORR (%) 15 10 5
16 mg/kg
Lonial S, et al. Lancet. 2016;387: Lonial S, et al. ASCO Abstract LBA8512.
Slide credit: clinicaloptions.com

31. Daratumumab Combinations in Myeloma: ORR With Rd vs Pd
Dara + Rd[1]
Dara + Pd[2]
100
sCR CR
VGPR PR
100
sCR CR
VGPR PR
ORR: 81% 80 80
25%
ORR: 71%
34% CR or better
9% CR or better 60 5% 60 4%
43% VGPR or better
ORR (%) 9%
63% VGPR or better
33%
ORR (%) 40
28% 40 20
28% 20
Dara, daratumumab; Pd, pomalidomide/dexamethasone; Rd, lenalidomide/dexamethasone; sCR, stringent CR; VGPR, very good PR.
19%
16 mg/kg
16 mg/kg
Clinical benefit rate (ORR + minimal response): 88%
ORR in double-refractory patients: 67%
Clinical benefit rate (ORR + minimal response): 74%
1. Plesner T, et al. ASH Abstract Chari A, et al. ASH Abstract 508.
Slide credit: clinicaloptions.com

32. CASTOR: PFS With Addition of Daratumumab to Vd
100
1-yr PFS 80
60.7% 60
PFS (%) 40
DVd Vd
Median PFS, Mos NR
7.2
26.9% 20
DVd, daratumumab/bortezomib/dexamethasone; NR, not reached; Vd, bortezomib/dexamethasone; VGPR, very good PR.
HR: 0.39 (95% CI: ; P < .0001) 3 6 9 12 15
Mos
Palumbo A, et al. ASCO Abstract LBA4. Reproduced with permission.
Slide credit: clinicaloptions.com

33. POLLUX: PFS with Addition of Daratumumab to Rd
12-mo PFS*
18-mo PFS*
100
83%
78% 80
DRd
60% 60
52%
PFS (%) Rd 40
Median PFS: 18.4 mos
DRd, daratumumab/lenalidomide/dexamethasone; Rd, lenalidomide/dexamethasone. 20
HR: 0.37 (95% CI: ; P < .0001) 3 6 9 12 15 18 21
Mos
63% reduction in the risk of disease progression or death for DRd vs Rd
Slide credit: clinicaloptions.com
Dimopoulos M, et al. EHA Abstract LB238.

34. Myeloma Treatment Prior to November 2015
Symptomatic relapse
Consider clinical trial
Factors to consider
Treatment-related factors
Disease-related factors
Pt-related factors
Relapse ≤ 12 mos
Newer combination strategies CRD, CPD, RVD or clinical trial
Allogeneic transplant clinical protocol
Prior SCT
No Prior SCT
Relapse > 12 months
Bortezomib ± Dexamethasone*
Lenalidomide + Dexamethasone*
Bortezomib ± PLD*
RVD, VTD, CFZ, CRD, VCD, RCD, DCEP±V, DT-PACE±V, cyclophosphamide, Pd, Td
Transplant eligible; good PS
Primary refractory-SCT
Relapsed/refractory-SCT
Transplant ineligible
If well tolerated and relapsed ≥ 6 mos after prior drug exposure
Repeat prior therapy
Otherwise, consider
Bortezomib ± dexamethasone*
Bortezomib + PLD*
Lenalidomide + dexamethasone*
RVD, VTD, CFZ, CRD, VCD, RCD, DCEP, DT-PACE ± V, cyclophosphamide, Pd, T
Subsequent relapse
Relapse with maintenance tx after SCT
Relapse without maintenance tx after SCT
Subsequent relapse
CFZ, carfilzomib; CRD, cyclophosphamide/lenalidomide/dexamethasone; DCEP, dexamethasone/cyclophosphamide/etoposide/cisplatin; DT-PACE, dexamethasone/thalidomide/cisplatin/doxorubicin/cyclophosphamide/etoposide; Pd, pomalidomide/dexamethasone; PLD, pegylated liposomal doxorubicin; PS, performance status; RVD, lenalidomide/bortezomib/dexamethasone; SCT, stem cell transplantation; T, thalidomide; tx, treatment; V, bortezomib; VCD, bortezomib/cyclophosphamide/dexamethasone; VTD, bortezomib/thalidomide/dexamethasone.
Relapse ≤ 36 mos
Relapse > 36 mos
Relapse > mos
Relapse ≤ mos
Subsequent relapse
SCT2
Subsequent relapse
Slide credit: clinicaloptions.com
Nooka AK, et al. Blood. 2015;125:

35. Go Online for More CCO Coverage of Myeloma!
Online Interactive Treatment Decision Tool CME-Certified Expert-Authored Modules Expert ClinicalThought Commentaries Interactive Virtual Presentation Downloadable Slidesets

36. Summary
New agents for pts with R/R MM clearly demonstrate continued improvement in the therapeutic options available
Introduction of monoclonal antibodies has shown significant efficacy and synergy with various backbone combinations
Optimal sequencing of these new agents and the optimal combination approaches are being investigated in ongoing clinical trials
Current treatment plans should be developed for each patient on an individual basis