6. Newly diagnosed MM
• Zimmerman et al (ASCO abs #8510)
• Phase II trial of Carfilzomib/lenalidomide/dex
(KRd) extended treatment
• KRd x 4 transplant CLD x 4 modified
KRd until cycle 18 lenalidomide maintenance
• Early outcomes:
– 88% with MRD-negative disease after cycle 8
– Median f/u of 9.7 months: 52/53 progression-free
“The results to date compare favorably to any
prior treatment of NDMM”
7. Newly diagnosed MM- transplant?
• Gay et al, EHA abs #S101
• Multicenter randomized phase 3 trial to compare ASCT
with conventional chemotherapy plus lenalidomide
• LD x 4 then tandem ASCT with melphalan 200 OR CRD
x 6
• N=389
• Median PFS was 42 months for MEL200-ASCT and 28
months for CRD (HR 0.67, 95% CI 0.48-0.93, P=0.014).
• The 4-year OS was 87% for MEL200-ASCT and 71% for
CRD (HR 0.51, 95% CI 0.28-0.93, P=0.028)
• Transplant toxicities were short-lived
8. Newly diagnosed MM
• Orchard et al, EHA Abs #P338
• Ranodmized phase 2 of of 90Y-labelled anti-
CD66 + melphalan 200 vs melphalan 200
alone
• Targets BM plasma cells for higher radiation
delivery
• Significant improvement in CR for patients in
Arm A compared to Arm B (50% vs 25%, odds
ratio [85% 1-sided CI]: 0.277 [0.102, 0.753]).
9. Newly diagnosed MM
• Straka et al, ASCO abs #8511
• Results from two phase III studies of bortezomib
(BTZ) consolidation vs observation (OBS) post-
transplant
• N=371
• Greater response of ≥ VGPR after BTZ consolidation
than OBS
• PFS was significantly improved by ~6 months
• No improvement in OS
• Possible most benefit for
– Pts in less than VGPR
– High risk cytogenetics
10.
11. Newly diagnosed MM
• Holstein et al, ASCO abs #8523
• Updated analysis of CALGB/ECOG/BMT CTN 100104:
Lenalidomide (Len) vs. placebo (PBO) for
maintenance post-auto transplant
• TTP is 53 mos for Len and 27 mos for PBO (hazard
ratio (HR):0.54 (p < 0.001)
• Median OS has not been reached for the Len arm and
is 76 mos for PBO (HR: 0.60, p = 0.001)
• SPM is higher for Len compared with PBO (p = 0.005)
• TTP and OS benefit with Len was observed regardless
of
• whether pts were in a complete response or not at
randomization and for thalidomide vs. Len induction
12. Newly diagnosed MM-transplant
ineligible
• Facon et al, ASCO abs #8524, updated EHA S105
• Update of FIRST trial
• SCT-ineligible NDMM pts, n=1623
• Randomized 1:1:1
– Continuous Rd (28-day cycles)
– Rd for 18 cycles (Rd18)
– MPT for 12 cycles (42-day cycles)
Rd Rd18 MPT
OS (months) 68.9 56.7 48.9
PFS2 (months) 42.9 40.0 35
HR Rd vs MPT + .75 (95% CI, 0.62-0.90)
13. Newly diagnosed MM (NDMM)
Induction
High dose
chemotherapy
+ ASCT
Maintenance
or
consolidation
+ maintenance
Consolidation/
maintenance
Relapse
Salvage
Car/len/
dex
Car/len/
dex
Y-anti CD66
Continuous Rd
Maint
len
Bortez
consol
15. Relapsed/refractory myeloma
• Dimopoulos et al, ASCO abs #8509 (ENDEAVOR study)
• Carfilzomib and dexamethasone (Kd) vs bortezomib and
dexamethasone (Vd)
• Stratification by prior treatment, ISS stage, prior lines of tx,
route of tx
• N= 929
• Kd: improvement in median PFS vs Vd (18.7 months [mo]
vs 9.4 mo; hazard ratio = 0.53; P< .0001)
• ORRs were 76.9% and 62.6% (P< .0001)
• OS data immature
• Kd had a favorable benefit-risk profile with similar AEs and
less PN
16. Relapsed/refractory myeloma
• Dimopoulos et al, ASCO abs #8525
• Update of ASPIRE trial
• Carfilzomib, lenalidomide, and dexamethasone
(KRd) vs lenalidomide and dexamethasone (Rd)
• Secondary analysis based on number of lines of
previous therapy
• KRd after first relapse:
– 1-year improvement in median PFS vs Rd
– 9-month improvement in median PFS vs Rd in pts with
≥ 2 prior lines of therapy,
This is a salvage regimen that can be used after several lines
of therapy.
17. Relapsed/refractory myeloma
• Jakubowiak, ASCO abs #8573
• Randomized phase II study of bortezomib
(Btz)/dexamethasone (dex) +/- elotuzumab
(Elo) (antibody against CS1 or SLAMF7)
• Median PFS was 9.7 mo (EBd) vs 6.9 mo (Bd)
(HR 0.71; 70% CI 0.58, 0.87; p = 0.08
• Early overall survival (OS): HR of 0.61 (70% CI
0.43, 0.85)
• Limited added toxicity of antibody therapy
18. Relapsed/refractory myeloma
• Lonial et al, NEJM August 2015
• ELOQUENT-2: A phase III, randomized study of
lenalidomide (Len)/dexamethasone (dex)
with/without elotuzumab (Elo)
• PFS: ELd 19.4 (16.6, 22.2) months, Ld 14.9
(12.1, 17.2) months (HR [95% CI] 0.70 [0.57,
0.85]; p = 0.0004
• ORR (95% CI) was 79% (74, 83) ELd, 66% (60,
71) Ld (p = 0.0002)
19. Relapsed/refractory myeloma
• San Miguel, ASCO abs #8526
• PANORAMA-1: Panobinostat plus bortezomib and
dexamethasone (improvement in PFS by 4 mo vs
PB/bortez/dex)
• Subanalysis of pts who received prior bortezomib
and IMiDs
• PFS PAN arm was 10.6 mo (95% CI, 7.6-13.8) vs 5.8
mo for PBO arm
• ORR 58.5% vs 41% (P = .0179)
• Similar safety profile
This regimen is likely useful after exposure to novel induction
regimens
20. Relapsed/refractory myeloma- single
arm studies
• CHAMPION-1, a phase I/II study of weekly
carfilzomib/ dexamethasone (Berenson et al, ASCO
abs #8527)
– ORR 72%
– Clinical benefit rate 80%
– PFS 10.6 months
• Phase II study of panobinostat/lenalidomide/
weekly dexamethasone (Chari et al, ASCO abs
#8528)
– ORR of 45%,
– CBR of 85 %
– PFS of 7.5 mo
21. Relapsed/refractory myeloma- single
arm studies
• A phase I/II trial of very low to low-dose continuous
azacitidine +Len/dex
– Twelve pts achieved > MR, 9 > PR (3 VGPR) ]
– 30% clinical benefit response (CBR) and 22.5% response
rates.
– Responses lasted between 3 months and 2 years
• Phase II study of daratumumab (DARA)
monotherapy (Lonial et al, ASCO abs #LBA8512)
– ORR 29.2%, with 3 sCR, 10 VGPR, and 18 PR
– 7.4 month median duration of response
– Median TTP 3.7 months
– Median OS has not been reached
– Estimated 1-year OS rate is 65%.
22. Relapsed/refractory myeloma- single
arm studies
• Berenson et al, ASCO abs #8591
• Pomalidomide (POM), dexamethasone (DEX),
and pegylated liposomal doxorubicin (PLD)
• N= 46
• ORR 35%
• clinical benefit rate 47%
• PFS 5.23 mo
• Main AE’s: cytopenias
23. Relapse options
• Carfilzomib and dexamethasone
• Carfilzomib, lenalidomide, and
dexamethasone
• Bortezomib/dexamethasone /elotuzumab
• Lenalidomide /dexamethasone /elotuzumab
• Panobinostat plus bortezomib
• Pomalidomide/dex
