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.

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 2015. Abstract S787. 2. Rosiñol L, et al. Blood. 2012;120:1589-1596. 3. Roussel M, et al. J Clin Oncol. 2014;32:2712-2717. 4. Bringhen S, et al. Blood. 2014;124:63-69. 5. Gay FM, et al. ASCO 2017. Abstract 8003. Slide credit: clinicaloptions.com

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, 15-16. †Cyclophosphamide: 300 mg/m2 Days 1, 8, 15. ‡Dexamethasone: 20 mg Days 1-2, 8-9, 15-16, 22-23. §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 2017. Abstract 8003. ClinicalTrials.gov. NCT02203643. Slide credit: clinicaloptions.com

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 (156.8-321) 10 (2) 241 (163-347) 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 2017. Abstract 8003.

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 2017. Abstract 8003.

FORTE: PBSC Mobilization Parameter KCd KRd P Value Median PBSC, 106/kg (IQR) 8.6 (7.0-11.3) 6.3 (4.5-8.8) < .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: 2.88-14.91; P < .001) Slide credit: clinicaloptions.com Gay FM, et al. ASCO 2017. Abstract 8003.

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 2017. Abstract 8003. Reproduced with permission.

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 2017. Abstract 8003. Slide credit: clinicaloptions.com

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