1. FORTE: Induction With Carfilzomib, Dexamethasone, and Cyclophosphamide or Lenalidomide in Newly Diagnosed MM
CCO Independent Conference Highlights* of the 2017 ASCO Annual Meeting; June 2-6, 2017; Chicago, Illinois
*Clinical Care Options (CCO) is an independent medical education organization that provides conference coverage and other unique educational programs for healthcare professionals
MM, multiple myeloma.
This activity is supported by educational grants from AbbVie, Amgen, AstraZeneca, Celgene Corporation, Genentech, Halozyme, Incyte, and Merck & Co., Inc.

2. FORTE: Background
Several regimens have been evaluated as pretransplant induction treatment in pts with newly diagnosed MM
≥ VGPR posttransplant: KRd, 96%[1]; VTD, 60%[2]; VRD, 58%[3]
KCd evaluated in elderly transplant-ineligible pts with newly diagnosed MM[4]
≥ VGPR postinduction: 71%
2-yr PFS of 76%, 2-yr OS of 87%
Current report a planned interim analysis of induction phase safety, PBSC mobilization, and preliminary efficacy with KCd vs KRd in newly diagnosed MM pts (cutoff: March 31, 2017)[5]
KCd, carfilzomib/cyclophosphamide/dexamethasone; KRd, carfilzomib/lenalidomide/dexamethasone; MM, multiple myeloma; PBSC, peripheral blood stem cell; VRD, bortezomib/lenalidomide/dexamethasone; VTD, bortezomib/thalidomide/dexamethasone.
1. Jakubowiak AJ, et al. EHA Abstract S Rosiñol L, et al. Blood. 2012;120: Roussel M, et al. J Clin Oncol. 2014;32: Bringhen S, et al. Blood. 2014;124: Gay FM, et al. ASCO Abstract 8003.
Slide credit: clinicaloptions.com

3. FORTE: Study Design Multicenter, randomized, open-label phase II study
Endpoints: induction phase safety, PBSC mobilization, preliminary efficacy
Pts with newly diagnosed MM, measurable disease per IMWG criteria, < 65 yrs of age, eligible for ASCT, Karnofsky score ≥ 60%, life expectancy ≥ 3 mos
(N = 477)
Arm A: KCd Induction
Carfilzomib* + cyclophosphamide† + dexamethasone‡
(n = 159)
Arm B: KRd Induction
Carfilzomib* + lenalidomide§ + dexamethasone‡
Arms A and B: Single ASCT + consolidation with induction regimen for 4 cycles
Arm C: consolidation with induction regimen for 8 cycles, no ASCT
Arm C: KRd Induction
*Carfilzomib: 36 mg/m2 IV Days 1-2 (20 mg/m2 Days 1-2, cycle 1), 8-9,
†Cyclophosphamide: 300 mg/m2 Days 1, 8, 15.
‡Dexamethasone: 20 mg Days 1-2, 8-9, 15-16,
§Lenalidomide: 25 mg Days 1-21.
PBSC Mobilization
Current report analyzed Arm B + Arm C together (n = 318)
Stratified by ISS, age
4 28-d cycles
ASCT, autologous stem cell transplantation; IMWG, International Myeloma Working Group; KCd, carfilzomib/cyclophosphamide/dexamethasone; KRd, carfilzomib/lenalidomide/dexamethasone; MM, multiple myeloma; PBSC, peripheral blood stem cell.
Gay FM, et al. ASCO Abstract 8003.
ClinicalTrials.gov. NCT
Slide credit: clinicaloptions.com

4. FORTE: Baseline Characteristics
KCd
(n = 154)
KRd
(n = 309)
Median age, yrs (IQR)
Age ≥ 60 yrs, n (%)
57 (52-62)
57 (37)
57 (51-62)
120 (39)
Male, n (%)
84 (55)
171 (55)
ISS stage, n (%) I II
III
80 (52)
48 (31)
26 (17)
158 (51)
97 (31)
54 (17)
Median LDH, IU/L (IQR)
Missing LDH data
226.5 ( )
10 (2)
241 ( )
Cytogenetic risk, n (%)
No t(4;14), t(14,16), del(17)
t(4;14) or t(14,16) or del(17)
Missing cytogenetic data
90 (58)
47 (31)
17 (11)
181 (59)
79 (26)
49 (16)
IQR, interquartile range; ISS, International Staging System; KCd, carfilzomib/cyclophosphamide/dexamethasone; KRd, carfilzomib/lenalidomide/dexamethasone; LDH, lactate dehydrogenase.
Slide credit: clinicaloptions.com
Gay FM, et al. ASCO Abstract 8003.

5. FORTE: Induction Phase Safety
Hematol. AEs, %
Grade 1/2
Grade 3/4 or SAE
KCd
KRd
≥ 1 AE 13 16 6 7
Thrombo-cytopenia 3* 8* 1 2
Neutropenia 3 5
Anemia 10
Nonhematol.
AEs, %
Grade 1-2
Grade 3/4 or SAE
KCd
KRd
≥ 1 AE
38*
55*
16*
32*
Dermatologic 3*
17* 1* 8*
Renal 3 2 1
Fever 11 17 4
Infections 6 10 5 GI
12*
28*
Hepatic
DVT 2† 8†
Hypertension
Cardiac
*P = .05 for comparison between arms.
AE-related d/c: KCd, 2%; KRd, 4%
Fewer dose reductions with KCd vs KRd (6% vs 15%; P = .005)
AE-related deaths: KCd, 2 cases (1 each of pneumonia, sudden death); KRd, 3 cases (1 each of sudden death during sepsis, infection, cardiac arrest after d/c for renal failure)
AE, adverse event; d/c, discontinuation; DVT, deep vein thrombosis; GI, gastrointestinal; KCd, carfilzomib/cyclophosphamide/dexamethasone; KRd, carfilzomib/lenalidomide/dexamethasone; SAE, serious adverse event.
*P < .001 for comparison between arms. †P = .01 for comparison between arms.
Slide credit: clinicaloptions.com
Gay FM, et al. ASCO Abstract 8003.

6. FORTE: PBSC Mobilization
Parameter
KCd
KRd
P Value
Median PBSC, 106/kg (IQR)
8.6 ( )
6.3 ( )
< .001
PBSC harvest, %
≥ 4 x 106/kg
≥ 2 and < 4 x 106/kg
< 2 x 106/kg (mobilization failure) 97 2 1 88 8 4
.002
.02 Ns
Pts requiring plerixafor, % 6 28
IQR, interquartile range; KCd, carfilzomib/cyclophosphamide/dexamethasone; KRd, carfilzomib/lenalidomide/dexamethasone; PBSC, peripheral blood stem cells.
Poor PBSC mobilization (harvest < 4 x 106/kg and/or requiring plerixafor) more likely with KRd vs KCd
OR: 6.55 (95% CI: ; P < .001)
Slide credit: clinicaloptions.com
Gay FM, et al. ASCO Abstract 8003.

7. FORTE: Preliminary Efficacy
sCR/CR
≥ nCR
≥ VGPR
≥ PR SD PD
96%
100
92% 90 80
74% 70
61% 60
Response (%) 50 40
31% 30
CR, complete response; KCd, carfilzomib/cyclophosphamide/dexamethasone; KRd, carfilzomib/lenalidomide/dexamethasone; nCR, near CR; PD, progressive disease. sCR, stringent CR; SD, stable disease.
20% 20
15% 6% 7% 10 3% 1% 1%
KCd
KRd
Gay FM, et al. ASCO Abstract Reproduced with permission.

8. FORTE: Conclusions
In pts with newly diagnosed MM, induction with KCd vs KRd was associated with lower rate of nonhematologic AEs and lower odds of poor PBSC mobilization, but lower rate of ≥ VGPR
Grade 3/4 nonhematologic AEs, KCd vs KRd: 16% vs 32% (P < .001)
PBSC harvest ≥ 4 x 106/kg, KCd vs KRd: 97% vs 88%
More pts on KRd required plerixafor (28% vs 6%)
≥ VGPR, KCd vs KRd: 61% vs 74% (P = .01)
Investigators concluded that safety profile of KCd was acceptable
AE, adverse event; KCd, carfilzomib/cyclophosphamide/dexamethasone; KRd, carfilzomib/lenalidomide/dexamethasone; PBSC, peripheral blood stem cells.
Slide credit: clinicaloptions.com
Gay FM, et al. ASCO Abstract 8003.
Slide credit: clinicaloptions.com

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