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(daratumumab)

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DARZALEX® (daratumumab)

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DARZALEX - CANDOR Study

Last Updated: 01/29/2026

SUMMARY

  • CANDOR is a randomized, open-label, multicenter, phase 3 study evaluating the efficacy and safety of DARZALEX for intravenous (IV) use in combination with carfilzomib and dexamethasone (D-Kd) vs carfilzomib and dexamethasone (Kd) in patients with relapsed or refractory multiple myeloma (RRMM).1
    • Dimopoulos et al (2020)2 reported the primary results of the CANDOR study with a median progression-free survival (PFS) follow-up of 16.9 months for D-Kd and 16.3 months for Kd. The median PFS in the D-Kd arm was not estimable (NE) vs 15.8 months in the Kd arm (hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.46-‍0.85; two-sided P=0.0027). The D-Kd vs Kd arm had a greater incidence of any grade adverse events (AEs; 99% vs 96%), grade ≥3 AEs (82% vs 74%), serious AEs (SAEs; 56% vs 46%), and fatal AEs (10% vs 5%).
    • Usmani et al (2023)3 reported the final efficacy and safety results of the CANDOR study after a median follow-up of approximately 50 months. The median PFS was 28.4 vs 15.2 months in patients treated with D-Kd vs Kd (HR, 0.64; 95% CI, 0.49-0.83). The D-Kd vs Kd arm had a greater incidence of any grade treatment-emergent adverse events (TEAEs; 99% vs 97%), grade ≥3 TEAEs (89% vs 78%), serious TEAEs (68% vs 52%), and fatal TEAEs (11% vs 6%).
  • Quach et al (2022)4reported the results of a subgroup analysis across frailty subgroups in patients with RRMM treated with D-Kd vs Kd. Efficacy and safety results were consistent with the primary analysis favoring D-Kd. Median PFS and ORR in D-Kd vs Kd was 18.5 vs 9.3 months (HR 0.66, 95% CI 0.38-1.14) and 75% vs 54% (odds ratio [OR] 2.39, 95% CI 1.09-5.22) for frail patients, respectively.
  • Other relevant literature regarding this topic have been included as citations for your review.5-10 

CLINICAL DATA

CANDOR (NCT03158688) was a randomized, open-label, multicenter, phase 3 study evaluating the efficacy and safety of D-Kd vs Kd in patients with RRMM.1

Study Design/Methods

  • Patients were randomized 2:1 to receive either of the following as 28-day cycles until disease progression1:
    • D-Kd:
      • DARZALEX 16 mg/kg IV weekly cycles 1-2 (first dose split over days 1 and 2 [8 mg/kg each] of cycle 1); every 2 weeks cycles 3-6; every 4 weeks thereafter
      • Carfilzomib 56 mg/m2 IV on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle (20 mg/m2 on days 1, 2 of cycle 1, 56 mg/m2 thereafter)
      • Dexamethasone 40 mg orally or IV weekly (or 20 mg if ≥75 years starting on the second week)
    • Kd: Carfilzomib and dexamethasone as above.
  • Key eligibility criteria: RRMM; 1-3 prior therapies with partial response or better (≥PR) to ≥1 prior therapy; Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-2; creatinine clearance ≥20 mL/min; left ventricular ejection fraction ≥40%.1 
  • Minimal residual disease (MRD) samples were collected at baseline and analyzed at 12 months for MRD-negativity (10-5) complete response (CR) rate.1
  • Primary endpoint: PFS1
  • Key secondary endpoints: Overall response rate (ORR), MRD (10-5 sensitivity), safety, rate of ≥CR, and overall survival (OS)1

Primary Efficacy and Safety Results of the CANDOR Study

Dimopoulos et al (2020)2 reported the primary results of CANDOR at a median follow-up of approximately 17 months.

Results

Patient Characteristics

Baseline Patient and Disease Characteristics1,2
Characteristic
D-Kd (n=312)
Kd (n=154)
Median age (range), years
64 (57-70)
65 (59-71)
ECOG PS, n (%)
0-1
295 (95)
147 (95)
2
15 (5)
7 (5)
ISS stage, n (%)
I
147 (47)
79 (51)
II
103 (33)
48 (31)
III
61 (20)
27 (18)
Cytogenetic risk by FISH, n (%)
Standard riska
104 (33)
52 (34)
High riskb
48 (15)
26 (17)
Unknownc
160 (51)
76 (49)
Number of prior therapies, n (%)
1
144 (46)
70 (45)
≥2
168 (54)
83 (55)
Prior therapies, n (%)
Bortezomib
287 (92)
134 (87)
Refractory to prior bortezomib
88 (28)
47 (31)
Lenalidomide
123 (39)
74 (48)
Refractory to prior lenalidomide
99 (32)
55 (36)
Abbreviations: D-Kd, DARZALEX + carfilzomib + dexamethasone; ECOG PS, Eastern Cooperative Oncology Group Performance Status; FISH, fluorescence in-situ hybridization; ISS, International Staging System; Kd, carfilzomib + dexamethasone.aPatients without t(4;14), t(14;16), and del(17p).bGenetic subtypes t(4;14), t(14;16), or del(17p).cPatients with FISH not done, failed, or of insufficient quantity.
Efficacy
  • Median PFS follow-up for the D-Kd vs Kd arms: 16.9 months vs 16.3 months.2 
  • Treatment with D-Kd resulted in a 37% reduction in the risk of progression or death (HR, 0.63; 95% CI, 0.46-0.85; two-sided P=0.0027).2
  • Median PFS for the D-Kd vs Kd arms: NE vs 15.8 months.2
  • Number of events that resulted in progression/death for the D-Kd vs Kd arms: 110 (35%) vs 68 (44%).2
  • The HR for PFS favored the D-Kd arm across other prespecified subgroups including age, International Staging System (ISS) stage, cytogenetic risk status, number of prior lines of therapy, lenalidomide-exposed patients, and lenalidomide-refractory patients. See Table: Progression-Free Survival in Select Prespecified Subgroups.1,2

Progression-Free Survival in Select Prespecified Subgroups1,2
Subgroup
D-Kd
(n=312)
Kd
(n=154)
HR for D-Kd vs Kd
(95% CI)
All randomized patients
312
154
0.63 (0.46-0.85)
ISS stage per IXRS at screening
1 or 2
252
127
0.61 (0.43-0.86)
3
60
27
0.72 (0.38-1.39)
Age at baseline, years
≤65
178
80
0.57 (0.38-0.86)
>65
134
74
0.76 (0.48-1.22)
Cytogenetic risk group
High risk
48
26
0.70 (0.36-1.40)
Standard risk
104
52
0.50 (0.28-0.90)
Unknown
160
76
0.66 (0.43-1.02)
Number of prior lines of therapy
1
133
67
0.68 (0.40-1.14)
≥2
179
87
0.61 (0.42-0.88)
Prior lenalidomide exposure
Yes
123
74
0.53 (0.34-0.82)
No
189
80
0.71 (0.45-1.12)
Refractory to lenalidomide
Yes
99
55
0.47 (0.29-0.78)
No
213
99
0.74 (0.49-1.11)
Abbreviations: CI, confidence interval; D-Kd, DARZALEX + carfilzomib + dexamethasone; ECOG PS, Eastern Cooperative Oncology Group Performance Status; HR, hazard ratio; ISS, International Staging System; IXRS, interactive response system; Kd, carfilzomib + dexamethasone.

ResponseRatesa and MRD-Negative Rates1,2
Response rates, %
D-Kd (n=312)
Kd (n=154)
P value
ORR
84
75
0.0080
≥VGPR
69
49
-
CR
29
10
-
MRD-negativity (10-5)
   MRD-negativity at 12 months
18
4
<0.0001
   MRD-negative CR at 12 months
13
1
<0.0001
   Best MRD-negative CR
14
3
-
Abbreviations: CR, complete response; D-Kd, DARZALEX + carfilzomib + dexamethasone; Kd, carfilzomib + dexamethasone; MRD, minimal residual disease; ORR, overall response rate; PR, partial response; VGPR, very good partial response.aMedian time to first response was 1 month in both arms.
  • After a median follow-up of 17.2 and 17.1 months in the D-Kd and Kd arms, respectively, the median OS was NE in both arms (HR, 0.75; 95% CI, 0.49-1.13; P=0.17).2
Safety

Treatment Exposure1
Parameter
D-Kd (n=308)
Kd (n=153)
Median duration of treatment, weeks
Carfilzomib
58.4
40.3
Dexamethasone
69.1
40.0
DARZALEX
68.1
-
Median relative dose intensity (range), %
Carfilzomib
90.8 (21.6-106.0)
93.3 (40.1-105.9)
Dexamethasone
90.6 (28.0-102.6)
91.9 (29.1-170.0)
DARZALEX
95.6 (24.0-102.4)
-
Abbreviations: D-Kd, DARZALEX + carfilzomib + dexamethasone; Kd, carfilzomib + dexamethasone.

Treatment-Emergent Adverse Events1,2
Adverse events, n (%)
D-Kd (n=308)
Kd (n=153)
All Grades (≥20%)
Grade 3 (≥5%)
Grade 4 (≥5%)
All Grades (≥20%)
Grade 3 (≥5%)
Grade 4 (≥5%)
TEAEs
306 (99)
-
-
147 (96)
-
-
Hematologica
   Thrombocytopenia
115 (37)
49 (16)
26 (8)
45 (29)
19 (12)
6 (4)
   Anemia
101 (33)
48 (16)
3 (1)
48 (31)
21 (14)
1(1)
   Neutropenia
43 (14)
24 (8)
2 (1)
15 (10)
7 (5)
2 (1)
   Lymphopenia
27 (9)
9 (3)
12 (4)
12 (8)
9 (6)
2(1)
Nonhematologica
   Diarrhea
97 (31)
12 (4)
0
22 (14)
1 (1)
0
   Hypertension
94 (31)
54 (18)
0
42 (27)
20 (13)
0
   URTI
90 (29)
7 (2)
1 (<1)
35 (23)
2 (1)
0
   Fatigue
75 (24)
23 (7)
1(<1)
28 (18)
7 (5)
0
   Dyspnea
61 (20)
12 (4)
0
34 (22)
4 (3)
0
   Pneumonia
55 (18)
32 (10)
5 (2)
19 (12)
12(8)
1 (1)
   Serious
173 (56)
-
-
70 (46)
-
-
Leading to treatment discontinuation
69 (22)
-
-
38 (25)
-
-
Leading to treatment dose reduction
119 (39)
-
-
53 (35)
-
-
Abbreviations: D-Kd, DARZALEX + carfilzomib + dexamethasone; Kd, carfilzomib + dexamethasone; TEAE, treatment-emergent adverse event; URTI, upper respiratory tract infection.aHematologic and nonhematologic adverse events of all grades were reported for those that occurred in ≥20% of patients in either arm. Grade ≥3 events reported for those that occurred in >5% of patients in either arm.

Adverse Events of Interest1,2
Adverse events, n (%)
D-Kd (n=308)
Kd (n=153)
All Grades
Grade 3 (≥5%)
Grade 4 (≥5%)
All Grades
Grade 3 (≥5%)
Grade 4 (≥5%)
Respiratory tract infection
225 (73)
77 (25)
7 (2)
84 (55)
22 (14)
1 (1)
Viral infections
63 (20)
19 (6)
0
22 (14)
2 (1)
0
DARZALEX-related infusion reactions
56 (18)
7 (2)
0
0
0
0
Peripheral neuropathy
53 (17)
3 (1)
0
13 (8)
0
0
Cardiac failurea
23 (7)
9 (3)
1 (<1)
16 (10)
10 (7)
3 (2)
Acute renal failure
18 (5.8)
5 (2)
4 (1)
12 (8)
6(4)
4 (3)
Ischemic heart disease
13 (4)
7 (2)
2 (1)
5 (3)
4 (3)
0
Abbreviations: D-Kd, DARZALEX + carfilzomib + dexamethasone; Kd, carfilzomib + dexamethasone; IRR, infusion-related reaction.aIncidence of cardiac failure leading to carfilzomib discontinuation was 3.9% in the D-Kd arm vs 4.6% in Kd arm.

Adverse Events Leading to Treatment Discontinuation1,2
D-Kd (n=308)
Kd (n=153)
Adverse Events leading to treatment discontinuation, n (%)
69 (22)
38 (25)
Adverse Events leading to carfilzomib discontinuation, n (%)
65 (21)
33 (22)
Adverse Events leading to DARZALEX discontinuation, n (%)
28 (9)
-
Abbreviations: D-Kd, DARZALEX + carfilzomib + dexamethasone; Kd, carfilzomib + dexamethasone.

Fatal Events2
Fatal events, n (%)
D-Kd (n=308)
Kd (n=153)
Treatment-emergent
30 (10)a
8 (5)
Treatment-related
5 (1.6)b
0
Abbreviations: D-Kd, DARZALEX + carfilzomib + dexamethasone; Kd, carfilzomib + dexamethasone.aGenerally reported in older and more frail patients.bDue to pneumonia, sepsis with Clostridium difficile enterocolitis, septic shock in the setting of Pneumocystis carinii pneumonia; Acinetobacter infection, and cardiorespiratory arrest (n=1 each).

Final Efficacy and Safety Results of the CANDOR Study

Usmani et al (2023)3 reported the final efficacy and safety results of the CANDOR study after a median follow-up of approximately 50 months.

Results

Efficacy

Overall Survival and MRD-Negativity (10-5) Rates3
Parameter
D-Kd, % (95% CI)
(n=312)
Kd, % (95% CI)
(n=154)
MRD-negativity rate at 12 months
n=57
n=8
18.3 (14.1-23.0)
5.2 (2.3-10.0)
   OR (95% CI)
4.403 (2.007-9.656)
MRD-negative CR rate at 12 months
n=40
n=3
12.8 (9.3-17.0)
1.9 (0.4-5.6)
   OR (95% CI)
7.819 (2.364-25.858)
MRD-negativity rate at any time
n=87
n=14
27.9 (23.0-33.2)
9.1 (5.1-14.8)
   OR (95% CI)
4.222 (2.277-7.829)
MRD-negative CR rate at any time
n=68
n=12
21.8 (17.3-26.8)
7.8 (4.1-13.2)
   OR (95% CI)
3.551 (1.833-6.877)
Median PFS (95% CI), months
28.4 (22.7-36.2)a
15.2 (11.1-19.9)
   HR (95% CI)
0.64 (0.49-0.83)
Median OS (95% CI), months
50.8 (44.7-NE)
43.6 (35.3-NE)
   HR (95% CI); P value
0.784 (0.595-1.033); 0.0417b
Median TTNT (95% CI), months
37.4 (30.1-47.8)
17.8 (13.5-23.1)
Median dPFS2, months
44.6
35.5
   HR (95% CI)
0.800 (0.614-1.044)
Abbreviations: CI, confidence interval; CR, complete response; D-Kd, DARZALEX + carfilzomib + dexamethasone; dPFS2, derived time to subsequent disease progression or death; HR, hazard ratio; Kd, carfilzomib + dexamethasone; MRD, minimal residual disease; NE, not estimable; OR, odds ratio; OS, overall survival; PFS, progression-free survival; TTNT, time to next treatment.aMedian follow-up was ~39 months in the D-Kd arm.bAlthough there was a difference of 7.2 months in OS in favor of D-Kd, the 1-sided P value of 0.0417 did not meet the prespecified statistical significance level of 0.021 (1-sided). These results were generally consistent across the 4 prespecified OS sensitivity analyses.
  • Prespecified subgroup analyses showed an OS improvement in the D-Kd vs Kd arm in most subgroups.3
    • The greatest OS benefit of D-Kd was observed in patients with high-risk cytogenetics (HR, 0.52; 95% CI, 0.29-0.94) and ISS stage III at screening (HR, 0.58; 95% CI, 0.35-0.99).
  • In the D-Kd vs Kd arm, 49% (n=153) vs 68% (n=105) of patients received subsequent antimyeloma therapy, respectively.3
Safety

Treatment Exposure3
Parameter
D-Kd (n=308)
Kd (n=153)
Median duration of treatment, weeks (range)
79 (0.3-236) 
40 (0.3-236)
   Carfilzomib
61 (0.3236)
40 (0.3-235)
   DARZALEX
79 (0.1-236)
-
Median relative dose intensity (range),a %
   Carfilzomib
88.3 (21.6-106.0)
91.4 (34.3-105.9)
   DARZALEX
94.9 (24.0-102.3)
-
Abbreviations: D-Kd, DARZALEX + carfilzomib + dexamethasone; Kd, carfilzomib + dexamethasone.aRelative dose intensity is the actual dose intensity/planned dose intensity×100, where actual (planned) dose intensity is the actual (planned) cumulative dose (mg/kg) divided by the actual (planned) duration of drug administration (weeks).
  • The safety results were consistent with previous reports, and no new safety signals were identified with the longer follow-up. See Table: Safety Overview.11

Safety Overview11
Parameter 
D-Kd (n=308)
Kd (n=153)
Median relative dose intensity (range),a %
   Carfilzomib
88.3 (21.6-106.0)
91.4 (34.3-105.9)
   DARZALEX
94.9 (24.0-102.3)
-
Dose reductions due to TEAE, n (%)
141 (45.8)
59 (38.6)
   Carfilzomib
95 (30.8)
38 (24.8)
   DARZALEX
4 (1.3)
-
Grade ≥3 TEAEs, n (%)
273 (88.6)
120 (78.4)
   Exposure-adjusted rate (95% CI), per PY
149.6 (132.9-168.5)
144.7 (121.0-173.1)
Serious TEAEs, n (%)
211 (68.5)
80 (52.3)
   Exposure-adjusted rate (95% CI)
60.4 (52.7-69.1)
59.0 (47.4-73.4)
Abbreviations: CI, confidence interval; D-Kd, DARZALEX + carfilzomib + dexamethasone; Kd, carfilzomib + dexamethasone; PY, patient years; TEAE, treatment-emergent adverse event.aRelative dose intensity is the actual dose intensity/planned dose intensity×100, where actual (planned) dose intensity is the actual (planned) cumulative dose (mg/kg) divided by the actual (planned) duration of drug administration (weeks).
  • Grade ≥3 infections and infestations occurred in 46% (n=142) vs 32% (n=49) of patients in the D-Kd vs Kd arm and led to carfilzomib discontinuation in 22% (n=69) vs 20% (n=30) of patients, respectively.3
  • TEAEs related to COVID-19 occurred in 11% (n=33) vs 4% (n=6) of patients in the D-Kd vs Kd arm, and deaths related to COVID-19 occurred in 2% (n=6) vs 1% (n=1) of patients, respectively.3
  • The incidence of carfilzomib and DARZALEX discontinuation due to TEAEs decreased over time, with most discontinuations due to TEAEs occurring in the first 18 months. See Table: TEAEs Leading to Treatment Discontinuation.11

TEAEs Leading to Treatment Discontinuation11
Parameter 
D-Kd (n=308)
Kd (n=153)
Discontinuation due to TEAE, n (%)
105 (34.1)
41 (26.8)
   Carfilzomib
98 (31.8)
37 (24.2)
   DARZALEX
43 (14.0)
-
Abbreviations: D-Kd, DARZALEX + carfilzomib + dexamethasone; Kd, carfilzomib + dexamethasone; TEAE, treatment-emergent adverse event.
  • The most common causes of fatal TEAEs were infections (D-Kd, 7% [n=21]; Kd, 3% [n=5]) and cardiac disorders (D-Kd, 2% [n=6]; Kd, 0%).3
    • In the D-Kd vs Kd arm, the exposure-adjusted rates of fatal TEAEs were 6.5 vs 5.6 per 100 patients-years, respectively.
    • In the D-Kd vs Kd arm, the fatal infection rates were 7% (n=21) vs 3% (n=5), and the exposure-adjusted fatal infection rates were 3.5 vs 2.55 per 100 patient-years, respectively.
  • TEAEs are summarized in Tables: TEAEs in the Safety Population, TEAEs of Interest, and Fatal Events.3

TEAEs in the Safety Population3
Adverse Events, n (%)
D-Kd (n=308)
Kd (n=153)
Any Gradea
Grade ≥3b
Any Gradea
Grade ≥3b
All TEAEs
306 (99.4)
273 (88.6)
149 (97.4)
120 (78.4)
Hematologic
   Thrombocytopenia
119 (38.6)
76 (24.7)
46 (30.1)
25 (16.3)
   Anemia
114 (37.0)
54 (17.5)
52 (34.0)
25 (16.3)
   Neutropenia
49 (15.9)
31 (10.1)
15 (9.8)
10 (6.5)
   Lymphopenia
29 (9.4)
22 (7.1)
13 (8.5)
11 (7.2)
Nonhematologic
   Diarrhea
118 (38.3)
18 (5.8)
28 (18.3)
1 (0.7)
   Hypertension
115 (37.3)
72 (23.4)
49 (32.0)
27 (17.6)
   Upper respiratory tract infection
105 (34.1)
12 (3.9)
37 (24.2)
2 (1.3)
   Fatigue
81 (26.3)
25 (8.1)
29 (19.0)
7 (4.6)
   Pneumonia
79 (25.6)
57 (18.5)
24 (15.7)
14 (9.2)
   Dyspnea
70 (22.7)
16 (5.2)
35 (22.9)
4 (2.6)
   Pyrexia
66 (21.4)
6 (1.9)
27 (17.6)
2 (1.3)
   Insomnia
64 (20.8)
16 (5.2)
19 (12.4)
3 (2.0)
   Back pain
63 (20.5)
7 (2.3)
21 (13.7)
2 (1.3)
   Nausea
62 (20.1)
0
22 (14.4)
1 (0.7)
   Hyperglycemia
31 (10.1)
16 (5.2)
13 (8.5)
5 (3.3)
   Cataract
34 (11.0)
15 (4.9)
13 (8.5)
8 (5.2)
Abbreviations: D-Kd, DARZALEX + carfilzomib + dexamethasone; Kd, carfilzomib + dexamethasone; TEAE, treatment-emergent adverse event.aAny grade TEAEs occurring in ≥20% of patients.bGrade ≥3 TEAEs occurring in ≥5% of patients.

TEAEs of Interest3
Adverse Events, n (%)
D-Kd (n=308)
Kd (n=153)
Any Gradea
Grade ≥3b
Any Gradea
Grade ≥3b
Respiratory tract infection
243 (78.9)
117 (38.0)
90 (58.8)
27 (17.6)
Infusion reaction (on same day as any carfilzomib dosing)
142 (46.1)
47 (15.3)
50 (32.7)
12 (7.8)
Peripheral neuropathy
66 (21.4)
6 (1.9)
15 (9.8)
1 (0.7)
Cardiac failure
29 (9.4)
12 (3.9)
17 (11.1)
13 (8.5)
Acute renal failure
25 (8.1)
11 (3.6)
14 (9.2)
10 (6.5)
Ischemic heart disease
19 (6.2)
16 (5.2)
8 (5.2)
5 (3.3)
Abbreviations: D-Kd, DARZALEX + carfilzomib + dexamethasone; Kd, carfilzomib + dexamethasone; TEAE, treatment-emergent adverse event.
aAny grade TEAEs occurring in ≥20% of patients.
bGrade ≥3 TEAEs occurring in ≥5% of patients.

Fatal Events3,11
Fatal AEs, n (%)
D-Kd (n=308)
Kd (n=153)
Treatment-emergenta
35 (11.4)
9 (5.9)
Treatment-related
5 (2%)b
-
Abbreviations: CI, confidence interval; D-Kd, DARZALEX + carfilzomib + dexamethasone; Kd, carfilzomib + dexamethasone.aExcludes the fatal TEAE of plasma cell myeloma.bDue to pneumonia, sepsis, septic shock, Acinetobacter infection, and cardiorespiratory arrest (n=1 each).

Impact of Frailty on Efficacy and Safety in the CANDOR Study

Quach et al (2022)4conducted a subgroup analysis of frailty status in patients in the CANDOR study.

Study Design/Methods

  • Patients were categorized as fit, intermediate (int), or frail based on a frailty score of 0, 1, or ≥2.4 
  • Scoring used an algorithm based on the International Myeloma Working Group (IMWG) frailty index: the final score is based on age (0 if ≤75 years, 1 if 76-80 years, 2 if >80 years), modified Charlson Comorbidity Index (CCI; 0 if CCI ≤1, 1 if CCI >1), and ECOG PS; 0 if ECOG PS=0, 1 if ECOG PS=1, and 2 if ECOG PS=2.4

Results

Patient Characteristics
  • Patients were stratified based on frailty status4:
    • Frail patients: 25% vs 27% for D-Kd vs Kd, respectively.
    • Int patients: 43% vs 36% for D-Kd vs Kd, respectively.
    • Fit patients: 27% vs 35% for D-Kd vs Kd, respectively.
  • Median duration of treatment among frailty status4:
    • Frail patients: 51 weeks vs 21 weeks for D-Kd vs Kd, respectively.
    • Int patients: 82 weeks vs 31 weeks for D-Kd vs Kd, respectively.
    • Fit patients: 99 weeks vs 68 week for D-Kd vs Kd, respectively.
  • Patients with prior transplant were more prevalent in the D-Kd vs Kd arms for frail (41% vs 27%) and int (65% vs 36%) subgroups, respectively.4
  • Fewer patients among the frail subgroup were lenalidomide exposed (37% vs 61%) and lenalidomide refractory (25% vs 46%) in the D-Kd vs Kd arm, respectively.4
Efficacy
  • Median PFS in D-Kd vs Kd was 18.5 vs 9.3 months (HR 0.66; 95% CI, 0.38-1.14) for frail patients, not reached (NR) vs 11.1 months (HR 0.44; 95% CI, 0.285-0.69) for int patients, NR vs 17.6 months (HR 0.64; 95% CI, 0.38-1.07) for fit patients.4
  • Response rates for D-Kd vs Kd arms are summarized in the Table: Response Rates.4

Response Rates4
Response Rates, n (%)
Frail
Intermediate
Fit
D-Kd (n=79)
Kd (n=41)
OR
(95% CI)
D-Kd (n=135)
Kd (n=56)
OR
(95% CI)
D-Kd (n=84)
Kd (n=54)
OR
(95% CI)
ORR
59 (75)
22 (54)
2.39
(1.09-5.22)
117 (87)
39 (70)
2.95
(1.31-6.62)
75 (89)
48 (89)
1.09
(0.35-3.38)
CR
15 (19)
3 (7)
-
46 (34)
6 (11)
-
37 (44)
9 (17)
-
VGPR
29 (37)
13 (32)
-
52 (39)
18 (32)
-
28 (33)
21 (39)
-
PR
15 (19)
6 (15)
-
19 (14)
15 (27)
-
10 (12)
18 (33)
-
Abbreviations: CR, complete response; D-Kd, DARZALEX + carfilzomib + dexamethasone; Kd, carfilzomib + dexamethasone; OR, odds ratio; ORR, overall response rate; PR, partial response; VGPR, very good partial response.
Safety

Treatment-Emergent Adverse Events in the Safety Population4
Events, n (%)
Frail
Intermediate
Fit
D-Kd (n=84)
Kd (n=54)
D-Kd (n=134)
Kd (n=56)
D-Kd (n=77)
Kd (n=40)
All TEAEs
 84 (100)
52 (96)
134 (100)
54 (96)
76 (99)
39 (98)
   Grade ≥3 TEAE
73 (87)
38 (70)
113 (84)
40 (71)
70 (91)
36 (90)
   Fatal TEAEa
3 (4)
1 (2)
15 (11)
5 (9)
12 (16)
3 (8)
   Carfilzomib
   discontinuation due to
   TEAE
21 (25)
9 (17)
30 (22)
16 (29)
27 (35)
9 (23)
TEAEs of interest,b grade ≥3
   Acute renal failure
0
0
4 (3)
8 (14)
6 (8)
2 (5)
   Cardiac arrhythmias
3 (4)
0
1 (1)
3 (5)
6 (8)
1 (3)
   Cardiac failure
2 (2)
3 (6)
5 (4)
4 (7)
4 (5)
6 (15)
   Dyspnea
2 (2)
1 (2)
6 (5)
2 (4)
6 (8)
1 (3)
   Hypertension
20 (24)
6 (11)
29 (22)
10 (18)
14 (18)
7 (18)
   Infusion reactionc
13 (16)
1 (2)
18 (13)
2 (4)
11 (14)
5 (13)
   Peripheral neuropathy
5 (6)
0
1 (1)
0
0
0
   Respiratory tract
   infection
25 (30)
11 (20)
49 (37)
8 (14)
26 (34)
5 (13)
   Viral infection
7 (8)
1 (2)
12 (9)
1 (2)
2 (3)
1 (3)
DARZALEX-related infusion reactiond
2 (2)
0
2 (2)
0
3 (4)
0
Abbreviations: D-Kd, DARZALEX + carfilzomib + dexamethasone; Kd, carfilzomib + dexamethasone; TEAE, treatment-emergent adverse event.
aIncludes patients with TEAE of disease progression/plasma cell myeloma.
bBy preferred term.
cEvent on same date of any carfilzomib dosing.dEvent on same date or next date of any DARZALEX dosing.

Literature Search

A literature search of MEDLINE®, Embase®, BIOSIS Previews®, and Derwent Drug File  (and/or other resources, including internal/external databases) was conducted on 24 June 2025. The search was limited to publications from 2020 to present.

 

References

Show
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2 Dimopoulos M, Quach H, Mateos MV, et al. Carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma (CANDOR): results from a randomised, multicentre, open-label, phase 3 study. Lancet. 2020;396(10245):186-197.  
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4 Quach H, Leleu X, Mateos M, et al. P907: Carfilzomib, dexamethasone, and daratumumab (Kdd) vs carfilzomib and dexamethasone (Kd) in relapsed/refractory multiple myeloma (RRMM): Frailty Subgroup Analysis of the Candor Study. Hemasphere. 2022;6(Suppl):798-799.  
5 Weisel K, Geils G, Karlin L, et al. Carfilzomib, Dexamethasone, and Daratumumab Versus Carfilzomib and Dexamethasone in Relapsed or Refractory Multiple Myeloma: Subgroup Analysis of the Phase 3 CANDOR Study in Patients With Early or Late Relapse. presented at: 62nd American Society of Hematology (ASH) Annual Meeting & Exposition; December 5-8, 2020; Virtual.  
6 Landgren O, Weisel K, Dachs L, et al. Evaluation of Minimal Residual Disease (MRD) Negativity in Patients with Relapsed or Refractory Multiple Myeloma Treated in the CANDOR Study. Poster presented at: 62nd American Society of Hematology (ASH) Annual Meeting & Exposition; December 5-8, 2020; Virtual.  
7 Weisel K, Mateos MV, Landgren O, et al. Health-related quality of life in patients with relapsed/refractory multiple myeloma treated with carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone: an analysis of patient-reported outcomes from the phase 3 CANDOR trial. [published online ahead of print February 19, 2025]. Clin Lymphoma Myeloma Leuk. 2025. doi:10.1016/j.clml.2025.02.005.  
8 Landgren O, Weisel K, Rosinol L, et al. Subgroup analysis based on cytogenetic risk in patients with relapsed or refractory multiple myeloma in the CANDOR study. Br J Haematol. 2022;198(6):988-993.  
9 Quach H, Nooka A, Samoylova O, et al. Carfilzomib, dexamethasone and daratumumab in relapsed or refractory multiple myeloma: results of the phase III study CANDOR by prior lines of therapy. British Journal of Haematology. 2021;194:784-788.  
10 Mateos M, Usmani S, Quach H, et al. Carfilzomib, dexamethasone, and daratumumab (KdD) vs Kd: subgroup analysis of the CANDOR study by prior autologous stem cell transplantation, lenalidomide exposure, or lenalidomide refractory disease. Abstract presented at: 18th International Myeloma Workshop (IMW); September 8-11, 2021; Vienna, Austria.  
11 Usmani S, Quach H, Mateos M, et al. Supplement to: Final analysis of carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone in the CANDOR Study. Blood Adv. 2023;7(14):3739-3748.