1. Addition of Daratumumab to Carfilzomib, Lenalidomide, and Dexamethasone 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. Daratumumab + KRd in Newly Diagnosed MM: Background
Standard of care for newly diagnosed MM: triplet regimens including PI and immunomodulatory agent with or without ASCT[1]
Carfilzomib, lenalidomide, and dexamethasone: triplet highly active in newly diagnosed MM[2,3]
Addition of ASCT associated with increased response and prolonged PFS[4]
Daratumumab: human anti-CD38 mAb approved as monotherapy and in combination for pts with relapsed/refractory MM[5]
Current study assessed tolerability, safety, activity of daratumumab addition to KRd in pts with newly diagnosed MM[1]
ASCT, autologous stem cell transplantation; KRd, carfilzomib/lenalidomide/dexamethasone; MM, multiple myeloma.
1. Jakubowiak AJ, et al. ASCO Abstract Jakubowiak AJ, et al. Blood. 2012;120: Korde N, et al. JAMA Oncol. 2015;1: Jakubowiak A, et al. EHA Abstract S Daratumumab [package insert]
Slide credit: clinicaloptions.com

3. Daratumumab + KRd in Newly Diagnosed MM: Study Design
Multicenter, open-label phase Ib study
Daratumumab: cycle 1: 8 mg/kg on Days 1-2; cycles 1-2: 16 mg/kg Q1W; cycles 3-6: 16 mg/kg Q2W; cycles > 6: 16 mg/kg Q4W
Carfilzomib: cycle 1, Day 1: 20 mg/m2; cycle 1, Day 8+: escalated to 70 mg/m2 weekly (Days 1, 8, 15)
Lenalidomide: 25 mg on Days 1-21
Dexamethasone: 40 mg weekly*
(N = 22)
Transplant-eligible and transplant-ineligible pts with newly diagnosed MM, no clinically significant cardiac disease
(N = 22)
Until elective discontinuation for ASCT or ≤ 13 cycles
*Pre- and postinfusion: dexamethasone 20 mg, diphenhydramine mg, paracetamol mg, montelukast 10 mg.
DoR, duration of response; IRR, infusion-related reaction; KRd, carfilzomib/lenalidomide/dexamethasone; MM, multiple myeloma; TTR, time to response.
Primary endpoints: safety, tolerability
Secondary endpoints: ORR, DoR, TTR, IRR
Exploratory endpoint: PFS
Slide credit: clinicaloptions.com
Jakubowiak AJ, et al. ASCO Abstract 8000.

4. Daratumumab + KRd in Newly Diagnosed MM: Baseline Characteristics
Pts
(N = 22)
Median age, yrs (range)
< 65 yrs, n (%)
65 to < 75 yrs, n (%)
59.5 ( )
15 (68)
7 (32)
Male, n (%)
12 (55)
Race, n (%)
White
Black
American Indian/Alaska Native NR
19 (86)
1 (5)
ECOG PS, n (%) 1 2
9 (41)
ECOG, Eastern Cooperative Oncology Group; KRd, carfilzomib/lenalidomide/dexamethasone; MM, multiple myeloma; NR, not reported; PS, performance status.
Slide credit: clinicaloptions.com
Jakubowiak AJ, et al. ASCO Abstract 8000.

5. Daratumumab + KRd in Newly Diagnosed MM: Tolerability and Infusion-Related Reactions
Median follow-up: 10.8 mos (range: )
Median cycles: 11.5 (range: )
19/22 pts escalated carfilzomib to 70 mg/m2 by cycle 2, Day 1
8/22 pts (36%) discontinued tx
ASCT: 6 (27%)
AE: 1 (5%)
PD: 1 (5%)
27% of pts experienced IRR
No grade 3/4
With first infusion: 5 pts (23%)
With later infusions: 1 pt (5%)
Lower IRR rate with first dosing split over Days 1-2
AE, adverse events; ASCT, autologous stem cell transplantation; IRR, infusion-related reaction; KRd, carfilzomib/lenalidomide/dexamethasone; MM, multiple myeloma; PD, progressive disease; tx, treatment.
Slide credit: clinicaloptions.com
Jakubowiak AJ, et al. ASCO Abstract 8000.

6. Daratumumab + KRd in Newly Diagnosed MM: Nonhematologic and Hematologic TEAEs
Nonhematologic TEAE in ≥ 30% Pts,* %
Daratumumab + KRd (N = 22)
All Grade
Grade 3/4
Diarrhea 73 14
URTI 59
Cough 55 5
Constipation 50
Fatigue
Dyspnea 46
Insomnia
Nausea 41
Rash
Back pain
Muscle spasm 36
Vomiting 32
Pain in extremity
Hematologic TEAE in ≥ 30% Pts, %
Daratumumab + KRd (N = 22)
All Grade
Grade 3/4
Lymphopenia 68 64
Thrombocytopenia 55 9
Anemia 46
Leukopenia 41
Neutropenia 32 14
ALT, alanine aminotransferase; KRd, carfilzomib/lenalidomide/dexamethasone; MM, multiple myeloma; TEAE, treatment-emergent adverse event; URTI, upper respiratory tract infection.
*Also included hyperglycemia (all grade: 32%; no grade 3/4) and increased ALT (all-grade: 32%; grade 3/4: 9%).
Slide credit: clinicaloptions.com
Jakubowiak AJ, et al. ASCO Abstract 8000.

7. Daratumumab + KRd in Newly Diagnosed MM: Serious TEAEs
Serious TEAE, n
Pts (N = 22)
Pulmonary embolism* 3
Pyrexia 2
Influenza
Abdominal pain 1
Chest pain
Dyspnea
Allergic dermatitis
Serious TEAE, n
Pts (N = 22)
Presyncope 1
Gastroenteritis
Lobular pneumonitis
Bacterial pneumonia
Tachycardia
Congestive heart failure
Hypertension
*1 pt had bilateral deep vein thrombosis and pulmonary embolism.
10/22 pts (46%) experienced serious TEAEs; all pts on aspirin prophylaxis
Likely related to: daratumumab, n = 3 (14%), carfilzomib, n = 5 (23%), lenalidomide, n = 5 (23%), dexamethasone, n = 2 (9%)
1 pt (5%) d/c for pulmonary embolism considered unrelated to daratumumab or carfilzomib
No change in LVEF measurements over time
d/c, discontinued; KRd, carfilzomib/lenalidomide/dexamethasone; LVEF, left ventricle ejection fraction; MM, multiple myeloma; TEAE, treatment-emergent adverse event.
Slide credit: clinicaloptions.com
Jakubowiak AJ, et al. ASCO Abstract 8000.

8. Daratumumab + KRd in Newly Diagnosed MM: Response
Median number of treatment cycles: 11.5 (range: )
After 4 Cycles, n = 21
After 8 Cycles, n = 15*
Best Response, n = 21
100
100
100
100
100
100 91 87 80 71 80 80 60 60 60
Response rate (%)
Response rate (%)
Response rate (%) 43 40 40 40 29 27 27 20 20 20 5 5
≥ PR
≥ CR
sCR
≥ PR
≥ CR
sCR
≥ PR
≥ CR
sCR
≥ VGPR
≥ VGPR
≥ VGPR
ASCT, autologous stem cell transplantation; KRd, carfilzomib/lenalidomide/dexamethasone; MM, multiple myeloma; PD, progressive disease.
Depth of response improved with duration of treatment
*5 pts who proceeded to ASCT before cycle 8 and 1 pt who discontinued due to PD at cycle 7 were excluded.
Median follow-up: 10.8 mos (range: )
OS: 100% at follow-up
Jakubowiak AJ, et al. ASCO Abstract Reproduced with permission.

9. Daratumumab + KRd in Newly Diagnosed MM: Investigator Conclusions
Daratumumab + KRd was well tolerated and safe in pts with newly diagnosed MM
IRR rate was low with split first dose (no grade 3/4 IRRs observed)
Daratumumab + KRd had 100% ORR in this pt population
≥ CR in 43%, ≥ VGPR in 91%
Responses improved with treatment duration
Investigators concluded that these results support further study of daratumumab + KRd in newly diagnosed MM and that daratumumab + KRd feasible as induction therapy
IRR, infusion-related reaction; KRd, carfilzomib/lenalidomide/dexamethasone; MM, multiple myeloma.
Slide credit: clinicaloptions.com
Jakubowiak AJ, et al. ASCO Abstract 8000.
Slide credit: clinicaloptions.com

10. Go Online for More CCO Coverage of ASCO 2017!
Short slideset summaries and additional CME-certified analyses with expert faculty commentary on key studies in:
Breast, gastrointestinal, genitourinary, lung, and skin cancers
Gynecologic and hematologic malignancies
clinicaloptions.com/oncology