DARZALEX®

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DARZALEX® (daratumumab)

Medical Information

DARZALEX - CANDOR Study

Last Updated: 07/14/2025

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^,²
- 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, 0.490.83). 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%).
Weisel et al (2025)⁴ reported the results of a post-hoc analysis of the CANDOR study evaluating patient-reported outcomes (PROs). Treatment impact on health-related quality of life (HRQoL) and disease symptoms was assessed using 3 clinical outcome assessment instruments. The change from baseline was similar between D-Kd and Kd arms for all scales.
Dimopoulous et al (2023)⁵ reported the results of a subgroup analysis of efficacy and safety by baseline renal function in patients with RRMM receiving D-Kd vs Kd in the CANDOR study. Consistent clinical benefit was seen in median PFS, overall response rate (ORR), and overall survival (OS) regardless of baseline renal function in D-Kd vs KD. Median PFS for patients with CrCl ≥15-<60 mL/min, ≥60-<90 mL/min, and ≥90 mL/min was 24.9 months vs 8.4 months (HR, 0.61; 95% CI, 0.35-1.06), 31.6 months vs 19.9 months (HR, 0.63; 95% CI 0.41-0.96), and 27.4 months vs 15.3 months (HR 0.64; 95% CI, 0.43-0.95), respectively. ORRs were 87% vs 50% (Odds ratio [OR], 8.02; 95% CI, 2.84-22.65); 85% vs 82% (OR 1.26; 95% CI 0.49-3.27); and 86% vs 80% (OR 1.59; 95% CI 0.69-3.68), respectively. Safety findings were consistent with the overall study population.
Quach et al (2022)⁶reported 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% (OR 2.39, 95% CI 1.09-5.22) for frail patients, respectively.
Landgren et al (2022)⁷ reported efficacy results of a subgroup analysis based on cytogenic risk in patients with RRMM in the CANDOR study. ORR was 81% vs 56% in high-risk and 87% vs 79% in standard-risk groups for D-Kd vs Kd, respectively. Median PFS was 11.2 vs 7.4 months in high-risk (HR, 0.56 [95% CI, 0.34, 0.93]) and not reached vs 16.6 months in standard-risk groups (0.56[95% CI, 0.39, 0.80)] for D-Kd vs Kd, respectively.
Quach et al (2021)⁸reported the results of a subgroup analysis by prior lines of therapy. Efficacy and safety results by subgroup were generally consistent with the primary analysis favoring D-Kd over Kd. PFS HRs for D-Kd vs Kd ranged from 0.47 to 0.84 across prior treatment subgroups. ORR and minimal residual disease (MRD)-negative complete response (CR) rates were higher for D-Kd vs Kd arms regardless of prior drug exposure or refractory status.
Mateos et al (2021)⁹ presented the efficacy and safety results of D-Kd vs Kd in patients with RRMM with or without prior autologous stem cell transplantation (ASCT) subdivided by lenalidomide-refractory and/or lenalidomide-exposed status. In patients with vs without prior ASCT, PFS HR was 0.54 vs 0.68 overall, 0.35 vs 0.62 for lenalidomide-exposed patients, and 0.30 vs 0.62 for lenalidomide-refractory patients. In patients with vs without prior ASCT, grade ≥3 AEs were reported in 89.6% vs 82.8% of patients in the D-Kd arm and in 78.7% vs 73.1% of patients in the Kd arm, with consistent rates across lenalidomide subgroups.
Suzuki et al (2021)¹⁰ reported the efficacy and safety results of D-Kd vs Kd from a post hoc analysis of the CANDOR study conducted in Asian patients with RRMM. PFS was NE for both the treatment arms. Grade ≥3 TEAEs occurred in 95.7% and 90.0% of patients in the D-Kd and Kd arms, respectively.
Siegel et al (2021)¹¹reported the results of patient-reported outcome (PRO) data collected during treatment. HRQoL scores were measured using the Global Health Status (GHS)/Quality of Life (QoL) domain of the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item (EORTC QLQ-C30). GHS/QoL completion rates were >81% for both arms. Overall, the least squares mean estimate (95% CI) of the difference between the two treatment arms was 0.06 (-2.39-2.50).
Chari et al (2021)¹² presented naïve comparison (without adjustments) and matching-adjusted indirect comparisons (MAIC) of PFS for D-Kd vs pomalidomide in combination with bortezomib and dexamethasone (PVd) vs DARZALEX in combination with pomalidomide and dexamethasone (DPd) in patients with RRMM. After naïve comparison, PFS benefit was observed for D-Kd vs PVd (median, 25.9 months vs 11.5 months; HR, 0.629; 95% CI, 0.397-0.747) and D-Kd vs DPd (median, 25.9 months vs 12.8 months; HR, 0.629; 95% CI, 0.445-0.890). After MAIC, PFS benefit was observed for D-Kd vs PVd (median: 25.0 months vs 11.5 months; HR, 0.539; 95% CI, 0.395-0.736) and D-Kd vs DPd (median, 25.0 months vs 12.8 months; HR, 0.677; 95% CI, 0.474-0.966). This analysis is referenced below.
Other relevant literature regarding this topic have been included as citations for your review.¹³^,¹⁴

PRODUCT LABELING

DARZALEX (daratumumab) [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.; www.janssenlabels.com/package-insert/product-monograph/prescribing-information/DARZALEX-pi.pdf

CLINICAL DATA

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

Study Design/Methods

Patients were randomized 2:1 to receive either of the following as 28-day cycles until disease progression:
- 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 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%
MRD samples were collected at baseline and analyzed at 12 months for MRD-negativity (10^-5) CR rate.
Primary endpoint: PFS
Key secondary endpoints: ORR, MRD (10^-5), safety, rate of ≥CR, and OS

Primary Efficacy and Safety Results of CANDOR

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

Results

Patient Characteristics

A total of 466 patients received either D-Kd (n=312) or Kd (n=154). Baseline patient and disease characteristics are summarized in Table: Baseline Patient and Disease 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 risk^a	104 (33)	52 (34)
High risk^b	48 (15)	26 (17)
Unknown^c	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
Treatment with D-Kd resulted in a 37% reduction in the risk of progression or death (HR, 0.63; 95% CI, 0.460.85; two-sided P=0.0027).
Median PFS for the D-Kd vs Kd arms: NE vs 15.8 months.
Number of events that resulted in progression/death for the D-Kd vs Kd arms: 110 (35%) vs 68 (44%).
The HR for PFS favored the D-Kd arm across other prespecified subgroups including age, International Staging System 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.
The response rates and MRD-negativity rates (10^-5) are summarized in the Table: Response Rates and MRD-Negative Rates.
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).

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.

ResponseRates^a 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.

Safety

The treatment exposure is summarized in the Table: Treatment Exposure.
The most common AE leading to DARZALEX treatment discontinuation was pneumonia (n=4 in the D-Kd arm; n=0 in the Kd arm) and cardiac failure for carfilzomib treatment discontinuation (n=6 in the D-Kd arm; n=3 in the Kd arm).
AEs are summarized in Tables: Treatment-Emergent Adverse Events, Adverse Events of Interest, Adverse Events Leading to Treatment Discontinuation and Fatal Events.

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)
Adverse events, n (%)	All Grades (≥20%)	Grade 3 (≥5%)	Grade 4 (≥5%)	All Grades (≥20%)	Grade 3 (≥5%)	Grade 4 (≥5%)
TEAEs	306 (99)	-	-	147 (96)	-	-
Hematologic^a
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)
Nonhematologic^a
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)
Adverse events, n (%)	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 failure^a	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 CANDOR

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

In the D-Kd vs Kd arm, median follow-up duration was 50.6 (range, 0-57) months vs 50.1 (range, 0-58) months.
Survival and MRD-negativity rates are summarized in Table: Overall Survival and MRD-Negativity (10^-5) Rates.
Prespecified subgroup analyses showed an OS improvement in the D-Kd vs Kd arm in most subgroups.
- 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 International Staging System (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.

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
MRD-negativity rate at 12 months	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
MRD-negative CR rate at 12 months	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
MRD-negativity rate at any time	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
MRD-negative CR rate at any time	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); 0.0417^b
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.

Safety

The treatment exposure is summarized in the Table: Treatment Exposure.
The safety results were consistent with previous reports, and no new safety signals were identified with the longer follow-up. See Table: Safety Overview.
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.
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.
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.
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%).
- 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 TEAEs.

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).

Safety Overview¹⁵

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).

TEAEs in the Safety Population³

Adverse Events, n (%)	D-Kd (n=308)		Kd (n=153)
Adverse Events, n (%)	Any Grade^a	Grade ≥3^b	Any Grade^a	Grade ≥3^b
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)
Adverse Events, n (%)	Any Grade^a	Grade ≥3^b	Any Grade^a	Grade ≥3^b
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.

TEAEs Leading to Treatment Discontinuation¹⁵

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.

Fatal Events³^,¹⁵

Fatal AEs, n (%)	D-Kd (n=308)	Kd (n=153)
Treatment-emergent^a	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).

Post-hoc Analysis of PROs

Weisel et al (2025)⁴ reported the results of a post-hoc analysis of the CANDOR study evaluating PROs. Disease-related symptoms and HRQoL were measured using the EORTC QLQ-C30, EORTC QLQ-MY20, and EQ-5D visual analog scale (VAS) tools.

Results

Patient Characteristics

A total of 466 patients were included in the analysis. The median duration of observation was 18.4 months (range, 0.9-50.2) in the D-Kd arm vs 10.3 months (range, 0.9-48.6) in the Kd arm. Baseline characteristics and PRO scores were balanced across groups; see Tables: Baseline Characteristics and PRO Scale Scores at Baseline.⁴

Baseline Characteristics⁴

Characteristic	D-Kd (n=312)	Kd (n=154)
Median age (range), years	64.0 (57-70)	64.5 (59-71)
Male, n (%)	135 (43)	63 (41)
ECOG PS, n (%)
0 or 1	295 (95)	147 (95)
2	15 (5)	7 (5)
Missing	2 (<1)	0
Previous therapy, n (%)
Transplant	195 (63)	75 (49)
CD38 antibody therapy	1 (<1)	0
PI	290 (93)	139 (90)
Immunomodulatory drug	206 (66)	110 (71)
Bortezomib	287 (92)	134 (87)
Refractory to any previous bortezomib-including regimen	88 (28)	47 (31)
Lenalidomide	123 (39)	74 (48)
Refractory to any previous lenalidomide-including regimen	99 (32)	55 (36)
Abbreviations: CD, cluster of differentiatio; D-Kd, DARZALEX + carfilzomib + dexamethasone; ECOG PS, Eastern Cooperative Oncology Group Performance Status; Kd, carfilzomib + dexamethasone; PI, proteasome inhibitor.

PRO Scale Scores at Baseline⁴

PRO Scale Score	D-Kd (n=312)	Kd (n=154)
EORTC QLQ-C30 scale score, mean (SD)^a
GHS/QoL	61.8 (20.37)	66.2 (19.19)
Physical functioning	76.7 (21.75)	80.9 (18.99)
Role functioning	75.0 (27.26)	75.8 (29.44)
Emotional functioning	81.2 (19.77)	80.8 (17.69)
Cognitive functioning	86.0 (17.77)	87.1 (17.84)
Social functioning	77.9 (26.85)	80.6 (26.89)
Fatigue	31.6 (24.12)	30.6 (24.55)
Nausea and vomiting	3.5 (11.09)	2.0 (7.08)
Pain	29.5 (28.25)	26.1 (27.51)
Dyspnea	12.9 (20.66)	12.7 (20.22)
Insomnia	19.6 (26.50)	18.9 (27.23)
Appetite loss	11.5 (20.73)	7.2 (18.72)
Constipation	10.8 (22.17)	7.4 (18.41)
Diarrhea	6.2 (15.95)	4.8 (13.04)
Financial difficulties	16.7 (25.17)	15.8 (25.17)
EORTC QLQ-MY20 scale score, mean (SD)^b
Disease symptoms	22.8 (19.96)	21.5 (19.75)
Effects of treatment	14.2 (13.17)	12.0 (12.42)
Future perspective	66.0 (26.43)	66.4 (26.30)
Body image	81.2 (27.53)	85.9 (21.23)
EQ-5D score, mean (SD)^c	67.0 (19.01)	71.5 (18.58)
Abbreviations: D-Kd, DARZALEX + carfilzomib + dexamethasone; EORTC QLQ-C30, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer–Core 30; EORTC QLQ-MY20, European Organization for Research and Treatment of Cancer Quality of Life Multiple Myeloma; GHS, global health status; HRQoL, health-relate quality of life; Kd, carfilzomib + dexamethasone; PRO, patient reported outcome; QoL, quality of life; SD, standard deviation; VAS, visual analog scale.^aEORTC QLQ-C30 scale scores range from 0 to 100, with higher scores indicating better HRQoL on the global and functional scales and greater symptom burden on the symptom scales. ^bEORTC QLQ-MY20 scale scores range from 0 to 100, with higher scores indicating a higher level of symptomatology (disease symptoms and side effects of treatment) or better functioning (future perspective and body image).^cEQ-5D VAS score ranges from 100, “the best health you can imagine,”to 0, “the worst health you can imagine.”

Efficacy

For the EORTC QLQ-C30 scales, the average scores over time were similar between groups and the score change relative to baseline were small for all scales.⁴
The changes relative to baseline were small and similar across arms for the EORTC QLQ-MY20 scales.⁴
For a summary of PRO scale scores LS mean differences between arms, see Table: Summary of PRO Scale Scores LS Mean Differences.⁴
Overall deterioration rates were similar in both arms for the EORTC QLQ-30 GHS/QoL scale. Median time to deterioration was longer for D-Kd (6.5 months) than for Kd
(3.9 months).
For the EORTC QLQ-MY20 disease symptom scale, the median time to deterioration was 13.9 months for D-Kd vs 7.4 months for Kd.
A subgroup analysis of patients with prior lenalidomide exposure (n=197) and lenalidomide-refractory patients (n=154) showed that changes from baseline in the EORTC QLQ-C30 scales were consistent with the full population.

Summary of PRO Scale Scores LS Mean Differences⁴

PRO Scale	LS Mean Difference for D-Kd-Kd (95% CI)
EORTC QLQ-C30 scales^a
GHS/QoL	0.1 (-2.4 to 2.6)
Physical functioning	0.0 (-2.5 to 2.5)
Role functioning	0.2 (-3.4 to 3.9)
Emotional functioning	0.6 (-2.0 to 3.2)
Cognitive functioning	-0.4 (-3.0 to 2.2)
Social functioning	-0.1 (-3.4 to 3.2)
Fatigue	1.4 (-1.8 to 4.5)
Nausea and vomiting	0.8 (-0.4 to 2.1)
Pain	-1.5 (-4.8 to 1.7)
Dyspnea	-1.5 (-4.9 to 1.9)
Insomnia	0.6 (-3.2 to 4.3)
Appetite loss	0.5 (-2.2 to 3.2)
Constipation	-0.2 (-3.0 to 2.7)
Diarrhea	0.9 (-1.7 to 3.5)
Financial difficulties	0.9 (-2.2 to 4.1)
EORTC QLQ-MY20 scales^b
Disease symptoms	-0.7 (-3.0 to 1.5)
Effects of treatment	0.8 (-1.1 to 2.6)
Future perspective	1.2 (-2.0 to 4.4)
Body image	1.1 (-2.7 to 4.9)
EQ-5D VAS	0.7 (-1.7 to 3.1)
Abbreviations: CI, confidence interval; D-Kd, DARZALEX + carfilzomib + dexamethasone; EORTC QLQ-C30, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer–Core 30; EORTC QLQ-MY20, European Organization for Research and Treatment of Cancer Quality of Life Multiple Myeloma; GHS, global health status; Kd, carfilzomib + dexamethasone; LS, least squares; PRO, patient reported outcome; QoL, quality of life; SD, standard deviation; VAS, visual analog scale.^aPositive differences for the LS mean difference favor D-Kd. ^bPositive differences for the LS mean difference favor D-Kd for the future perspective and body image scales; negative differences favor D-Kd for the disease symptoms and side effects of treatment scales.

Subgroup Analysis by Baseline Renal Function

Dimopoulous et al (2023)⁵ conducted a subgroup analysis of efficacy and safety by baseline renal function in patients in the CANDOR study.

Results

Patient Characteristics

A total of 466 patients were randomized with baseline characteristics generally balanced between treatment arms and renal subgroups and are detailed in Table: Baseline Characteristics by Renal Subgroups.
One patient in the D-Kd arm was excluded due to missing baseline CrCl.

Baseline Characteristics by Renal Subgroups⁵

Characteristic	≥15-<60 mL/min		≥60-<90 mL/min		≥90 mL/min
Characteristic	D-Kd (n=67)	Kd (n=36)	D-Kd (n=112)	Kd (n=57)	D-Kd (n=132)	Kd (n=61)
ISS stage at baseline^a, n (%)
I	2 (3)	3 (8)	14 (13)	7 (12)	21 (16)	15 (25)
II	19 (28)	13 (36)	29 (26)	16 (28)	34 (26)	11 (18)
III	13 (19)	7 (19)	7 (6)	7 (12)	5 (4)	0
Unknown	33 (49)	13 (36)	62 (55)	27 (47)	72 (55)	35 (57)
High risk cytogenetics^b, n (%)	15 (22)	9 (25)	16 (14)	11 (19)	17 (13)	6 (10)
Number of prior transplants, n (%)
1	23 (34)	8 (22)	57 (51)	26 (46)	81 (61)	32 (52)
2	7 (10)	1 (3)	9 (8)	4 (7)	16 (12)	4 (7)
>2	0	0	0	0	1 (1)	0
Number of prior therapies, n (%)
1	30 (45)	14 (39)	52 (46)	30 (53)	61 (46)	26 (43)
2-3	37 (55)	22 (61)	60 (54)	27 (47)	71 (54)	34 (56)
>3	0	0	0	0	0	1 (2)
Prior therapies, n (%)
Bortezomib	62 (93)	31 (86)	101 (90)	47 (82)	123 (93)	56 (92)
Lenalidomide	24 (36)	21 (58)	52 (46)	24 (42)	47 (36)	29 (48)
PI	63 (94)	33 (92)	103 (92)	49 (86)	123 (93)	57 (93)
IMiD	33 (49)	26 (72)	82 (73)	39 (68)	90 (68)	45 (74)
Abbreviations: D-Kd, DARZALEX + carfilzomib + dexamethasone; FISH, fluorescence in situ; IMiD, Immunomodulatory drugs; ISS, International Staging System; Kd, carfilzomib + dexamethasone; LDH, lactate dehydrogenase; PI, proteasome inhibitor. Excluded patient whose baseline renal impairment with missing value (D-Kd, n=1; Kd, n=0). ^aRevised ISS stage: R-Stage 1 and standard risk group by FISH and morla LDH; R-Stage 2: neither R-ISS stage 1 nor 3; and R-Stage 3: ISS stage 3 and (either high-risk group by FISH or high LDH). ^bThe high-risk group consisted of the genetic subtypes t(4; 14); t(14; 16), or deletion17p.

Efficacy

After a median follow up of approximately 50 months (data cutoff: April 15, 2022), D-Kd showed consistent clinical benefit irrespective of baseline renal function vs Kd in median PFS, ORR, and OS as detailed within the Table: Efficacy Outcomes by Renal Subgroups.

Efficacy Outcomes by Renal Subgroups⁵

Parameter	≥15-<60 mL/min		≥60-<90 mL/min		≥90 mL/min
Parameter	D-Kd (n=67)	Kd (n=36)	D-Kd (n=112)	Kd (n=57)	D-Kd (n=132)	Kd (n=61)
Median PFS, mo (95% CI)	24.9 (13.0-41.8)	8.4 (3.3-32.8)	31.6 (20.3-43.2)	19.9 (11.1-33.2)	27.4 (18.7-35.1)	15.3 (10.8-20.3)
HR, (D-Kd/KD) (95% CI)	0.61 (0.35-1.06)		0.63 (0.41-0.96)		0.64 (0.43-0.95)
Median OS, mo (95% CI)	44.6 (24.2-NE)	25.2 (12.4-NE)	48.0 (39.4-NE)	43.7 (35.4-NE)	NE (44.9-NE)	NE (34.6-NE)
HR, (D-Kd/KD) (95% CI)	0.58 (0.32-1.03)		0.91 (0.58-1.43)		0.74 (0.46-1.20)
ORR^a, n (%)	58 (87)	18 (50)	95 (85)	47 (82)	113 (86)	49 (80)
OR (D-Kd/Kd) (95% CI)	8.02 (2.84-22.65)		1.26 (0.49-3.27)		1.59 (0.69-3.68)
CR Rate^b, n (%)	24 (36)	3 (8)	49 (44)	12 (21)	50 (38)	13 (21)
OR (D-Kd/Kd) (95% CI)	7.43 (1.85-29.74)		3.17 (1.47-6.87)		2.20 (1.08-4.49)
Treatment duration, wks, median (range)	67 (0-227)	21 (0-222)	90 (1-236)	56 (1-222)	76 (0-236)	47 (1.3-236)
Abbreviations: D-Kd, DARZALEX + carfilzomib + dexamethasone; FISH, fluorescence in situ; IMiD, Immunomodulatory drugs; ISS, International Staging System; Kd, carfilzomib + dexamethasone; LDH, lactate dehydrogenase; PI, proteasome inhibitor. Excluded patient whose baseline renal impairment with missing value (D-Kd, n=1; Kd, n=0). ^aORR is defined as the proportion of intent-to-treat patients who achieve stringent CR, CR, very good partial response, or partial response per the International Myeloma Working Group Uniform Response Criteria (IMWG-URC) as their best response. ^bCR rate is defined as the proportion of intent-to-treat patients who achieve stringent CR or CR per International Myeloma Working Group Uniform Response Criteria (IMWG-URC) as their best response.

Safety

Safety findings were consistent with the overall study population and are summarized in Table: Most Common TEAEs by Renal Subgroups.

Most Common TEAEs by Renal Subgroups⁵

Most common TEAEs^a	≥15-<60 mL/min		≥60-<90 mL/min		≥90 mL/min
Most common TEAEs^a	D-Kd (n=66)	Kd (n=35)	D-Kd (n=110)	Kd (n=57)	D-Kd (n=131)	Kd (n=61)
Grade ≥3, n (%)	59 (89)	32 (91)	96 (87)	45 (79)	117 (89)	43 (70)
Thrombocytopenia	25 ()38)	8 (23)	23 (21)	10 (18)	28 (21)	7 (11)
Hypertension	16 (24)	7 (20)	24 (22)	13 (23)	32 (24)	7 (11)
Anemia	16 (24)	10 (29)	20 (18)	7 (12)	18 (14)	8 (13)
Pneumonia	15 (23)	3 (9)	20 (18)	6 (11)	22 (17)	5 (8)
TEAEs of interest, n (%)
Respiratory tract infections	21 (32)	5 (14)	46 (42)	11 (19)	49 (37)	11 (18)
Hypertension	17 (26)	7 (20)	25 (23)	14 (25)	32 (24)	7 (11)
Infusion reaction (on same date of any carfilzomib dosing)	9 (14)	4 (11)	16 (15)	5 (9)	22 (17)	3 (5)
Cardiac failure	3 (5)	4 (11)	5 (5)	6 (11)	4 (3)	3 (5)
Viral infection	3 (5)	0	10 (9)	0	9 (7)	3 (5)
Acute renal failure	4 (6)	4 (11)	4 (4)	4 (7)	3 (2)	2 (3)
Dyspnea	6 (9)	1 (3)	4 (4)	2 (4)	6 (5)	1 (2)
Abbreviations: D-Kd, DARZALEX + carfilzomib + dexamethasone; FISH, fluorescence in situ; Kd, carfilzomib + dexamethasone; TEAE, treatment emergent adverse event. Excluded patient whose baseline renal impairment with missing value (D-Kd, n=1; Kd, n=0). ^aGrade ≥3 TEAEs include those reported in ≥15% of patients. TEAEs of interest include those reported in ≥5% of patients

Impact of Frailty on Efficacy and Safety in the CANDOR Study

Quach et al (2022)⁶conducted 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.
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 Easter Cooperative Oncology Group performance status (ECOG PS; 0 if ECOG PS=0, 1 if ECOG PS=1, and 2 if ECOG PS=2).

Results

Patient Characteristics

Patients were stratified based on frailty status:
- 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 status:
- 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.
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.

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, 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.
Response rates for D-Kd vs Kd arms are summarized in the Table: Response Rates.

Response Rates⁶

Response Rates, n (%)	Frail			Intermediate			Fit
Response Rates, n (%)	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

Any grade TEAEs occurred in >95% of patients across arms and subgroups and are summarized in the Table: Treatment-Emergent Adverse Events in the Safety Population.

Treatment-Emergent Adverse Events in the Safety Population⁶

Events, n (%)	Frail		Intermediate		Fit
Events, n (%)	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 TEAE^a	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 reaction^c	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 reaction^d	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.

Subgroup Analysis Based on Cytogenetic Risk in the CANDOR Study

Landgren et al (2022)⁷ reported efficacy results of a subgroup analysis based on cytogenic risk in patients with RRMM in the CANDOR study.

Results

Patients with valid cytogenetic results are summarized in the Table: Summary of Cytogenetic Risk Groups.
Regardless of cytogenetic risk groups, ORR was higher in D-Kd vs Kd.
Response rates for D-Kd vs Kd arms are summarized in the Table: Overall Response Rates of Patients Across Cytogenetic Risk Subgroups.
PFS favored D-Kd vs Kd for all cytogenetic risk groups.
HR across cytogenetic risk groups are summarized in the Table: PFS Hazard Ratios Across Cytogenetic Risk Groups.

Overall Response Rates of Patients Across Cytogenetic Risk Subgroups⁷

	D-Kd (n=312)					Kd (n=154)					OR (95% CI)^a	P Value (2-sided)^b
	n/N	ORR, %	CR, n (%)	VGFR, n (%)	PR, n (%)	n/N	ORR, %	CR, n (%)	VGFR, n (%)	PR, n (%)	OR (95% CI)^a	P Value (2-sided)^b
All randomized patients	263/312	84.3	103 (33.0)	113 (36.2)	47 (15.1)	112/154	72.7	20 (13.0)	53 (34.4)	39 (25.3)	2.148 (1.328-3.475)	-
Cytogenetic risk group
High risk^c	56/69	81.2	16 (23.2)	26 (37.7)	14 (20.3)	20/36	55.6	0	11 (30.6)	9 (25.0)	3.73 (1.348-8.440)	0.5775
Standard risk^d	154/178	86.5	62 (34.8)	68 (38.2)	24 (13.5)	78/99	78.8	18 (18.2)	34 (34.3)	26 (26.3)	1.864 (0.958-3.624)	-
Unknown^e	53/65	81.5	25 (38.5)	19 (29.2)	9 (13.8)	14/19	73.7	2 (10.5)	8 (42.1)	4 (21.1)	2.679 (0.677-10.610)	-
With prior lenalidomide exposure
All Patients	97/123	78.9	38 (30.9)	41 (33.3)	18 (14.6)	53/74	71.6	8 (10.8)	28 (37.8)	17 (23.0)	1.565 (0.782-3.132)	-
Cytogenetic risk group
High risk^c	22/26	84.6	7 (26.9)	9 (34.6)	6 (23.1)	10/15	66.7	0	6 (40.0)	4 (26.7)	3.012 (0.635-14.290)	0.6809
Standard risk^d	57/72	79.2	22 (30.6)	26 (36.1)	9 (12.5)	38/52	73.1	6 (11.5)	19 (36.5)	13 (25.0)	1.437 (0.611-3.380)	-
Unknown^e	18/25	72.0	9 (36.0)	6 (24.0)	3 (12.0)	5/7	71.4	2 (28.6)	3 (42.9)	0	1.178 (0.136-10.172)	-
Without prior lenalidomide exposure
All Patients	166/189	87.8	65 (34.4)	72 (38.1)	29 (15.3)	59/80	73.8	12 (15.0)	25 (31.3)	22 (27.5)	2.770 (1.395-5.501)	-
Cytogenetic risk group
High risk^c	34/43	79.1	9 (20.9)	17 (39.5)	8 (18.6)	10/21	47.6	0	5 (23.8)	5 (23.8)	3.650 (1.155-11.535)	0.7284
Standard risk^d	97/106	91.5	40 (37.7)	42 (39.6)	15 (14.2)	40/47	85.1	12 (25.5)	15 (31.9)	13 (27.7)	2.049 (0.671-6.259)	-
Unknown^e	35/40	87.5	16 (40.0)	13 (32.5)	6 (15.0)	9/12	75.0	0	5 (41.7)	4 (33.3)	4.028 (0.577-28.112)	-
Abbreviations: CI, confidence interval; CR, complete response; D-Kd, DARZALEX + carfilzomib + dexamethasone; FISH, fluorescent in-situ hybridization; Kd, carfilzomib + dexamethasone; OR, odds ratio; ORR, overall response rate; PR, partial response; VGPR, very good partial response. ^aOdds ratio and corresponding 95% CIs were estimated using a stratified Mantel-Haenszel method as specified. ^bP values were calculated using Gail and Simon quantitative interaction tests. ^cIncludes patients who have any mutation of t(4;14), t(14;16); or deletion 17p13, while the other test may be unknown. ^dIncludes patients who have valid results without evidence of mutation of t(4;14), t(14;16); or deletion 17p13, while the other test may be unknown. ^eIncludes patients without FISH or seqFISH results, or with failed or insufficient sample quantity.

Summary of Cytogenetic Risk Groups¹⁶

	D-Kd (n=312)	Kd (n=154)	Total (n=466)
Patients with samples tested and valid results, n (%)	247 (79.2)	135 (87.7)	382 (82.0)
High risk^a	69 (22.1)	36 (23.4)	105 (22.5)
t(4; 14)	28 (9.0)	15 (9.7)	43 (9.2)
t(14; 16)	3 (1.0)	3 (1.9)	6 (1.3)
del(17p13)	44 (14.1)	23 (14.9)	67 (14.4)
Standard risk^b	178 (57.1)	99 (64.3)	277 (59.4)
Unknown^c	65 (20.8)	19 (12.3)	84 (18.0)
Abbreviations: D-Kd, DARZALEX + carfilzomib + dexamethasone; FISH, fluorescent in-situ hybridization; Kd, carfilzomib + dexamethasone. ^aIncludes genetic subtypes t(4;14); t(14;16); or del(17p13). ^bIncludes patients without t(4;14); t(14;16); or del(17p13). ^cIncludes patients without FISH or seqFISH results, or with failed or insufficient sample quantity.

PFS Hazard Ratios Across Cytogenetic Risk Groups⁷

	D-Kd (n=312)		Kd (n=154)		HR (95% CI)^b	P value (2-sided)^c
	n/N (%)	Median PFS (95% CI),^a months	n/N (%)	Median PFS (95% CI),^a months	HR (95% CI)^b	P value (2-sided)^c
All randomized patients	140/312 (44.9)	28.6 (22.7-NE)	85/154 (55.2)	15.2 (11.1-19.9)	0.59 (0.45-0.78)
Cytogenetic risk group						0.7575
High risk^d	45/69 (65.2)	11.2 (6.5-17.0)	26/36 (72.2)	7.4 (3.3-11.1)	0.56 (0.37-0.93)
Standard risk^e	69/178 (38.8)	NE (26.3-NE)	51/99 (51.5)	16.6 (12.3-28.0)	0.56 (0.39-0.80)
Unknown^f	26/65 (40.0)	NE (21.7-NE)	8/19 (42.1)	NE (9.9-NE)	0.79 (0.33-1.88)
With prior lenalidomide exposure
All Patients	57/123 (46.3)	25.9 (20.3-NE)	47/74 (63.5)	11.1 (7.6-14.9)	0.49 (0.33-0.74)
Cytogenetic risk group						0.4867
High risk^d	14/26 (53.8)	22.6 (6.5-NE)	12/15 (80.0)	9.3 (3.3-12.0)	0.35 (0.15-0.83)
Standard risk^e	32/72 (44.4)	28.1 (18.5-NE)	32/52 (61.5)	12.3 (7.6-15.7)	0.51 (0.31-0.85)
Unknown^f	11/25 (44.0)	NE (4.2-NE)	3/7 (42.9)	21.7 (2.1-NE)	0.93 (0.24-3.59)
Without prior lenalidomide exposure
All Patients	83/189 (43.9)	NE (19.2-NE)	38/80 (47.5)	21.3 (14.6-NE)	0.64 (0.43-0.96)
Cytogenetic risk group						0.9421
High risk^d	31/43 (72.1)	10.3 (5.8-16.8)	14/21 (66.7)	4.7 (1.9-19.9)	0.73 (0.37-1.42)
Standard risk^e	37/106 (34.9)	NE (27.4-NE)	19/47 (40.4)	28.0 (16.6-NE)	0.63 (0.35-1.13)
Unknown^f	15/40 (37.5)	NE (18.7-NE)	5/12 (41.7)	NE (7.4-NE)	0.72 (0.22-2.32)
Abbreviations: CI, confidence interval; D-Kd, DARZALEX + carfilzomib + dexamethasone; FISH, fluorescent in-situ hybridization; Kd, carfilzomib + dexamethasone; NE, not estimable; PD, progressive disease; PFS, progression free survival. ^aPFS is defined as time (in months) from randomization until PD or death due to any cause, whichever occurs first; medians were estimated using Kaplan-Meier method. Corresponding 95% CIs were estimated. ^bHazard ratios and corresponding 95% CIs were estimated using a stratified Cox proportional hazards model as specified. ^cP values were calculated using Gail and Simon quantitative interaction test. ^dIncludes patients who have any mutation t(4;14), t(14;16); or deletion 17p13.^eIncludes patients who have valid results without evidence of mutation of t(4;14), t(14;16), or deletion 17p13, while the other test may be unknown. ^fIncludes patients without FISH or seqFISH results, or with failed or insufficient sample quantity.

Subgroup Analysis by Prior Lines of Therapy

Quach et al (2021)⁸^,¹⁷ reported the results of a subgroup analysis by prior lines of therapy at a median follow-up of approximately 17 months.

Results

Patient Characteristics

Baseline characteristics were generally balanced between arms across subgroups, as presented in Tables: Baseline Characteristics by Number of Prior Lines of Therapy and Baseline Characteristics of Patients Either Refractory to Lenalidomide or Bortezomib/Ixazomib.

Baseline Characteristics by Number of Prior Lines of Therapy¹⁷

Characteristic	1 Prior Line		≥2 Prior Lines
Characteristic	D-Kd (n=133)	Kd (n=67)	D-Kd (n=179)	Kd (n=87)
Median age (range), years	63.0 (29-83)	66.0 (35-81)	65.0 (33-84)	63.0 (35-83)
ISS stage, n (%)
I	64 (48.1)	35 (52.2)	83 (46.4)	44 (50.6)
II	45 (33.8)	21 (31.3)	58 (32.4)	27 (31.0)
III	23 (17.3)	11 (16.4)	38 (21.2)	16 (18.4)
Unknown	1 (0.8)	0	0	0
Cytogenetic risk by FISH, n (%)
High risk^a	24 (18.0)	11 (16.4)	24 (13.4)	15 (17.2)
Standard risk^b	45 (33.8)	23 (34.3)	59 (33.0)	29 (33.3.)
Unknown^c	64 (48.1)	33 (49.3)	96 (53.6)	43 (49.4)
Median prior lines of therapy (range)	1.0 (1-2)	1.0 (1-1)	2.0 (1-3)	2.0 (1-4)
Prior therapies, n (%)
Bortezomib or ixazomib	117 (88.0)	55 (82.1)	172 (96.1)	82 (94.3)
Refractory to bortezomib or ixazomib^d	21 (15.8)	14 (20.9)	79 (44.1)	41 (47.1)
Lenalidomide	29 (21.8)	17 (25.4)	94 (52.5)	57 (65.5)
Refractory to lenalidomide	19 (14.3)	6 (9.0)	80 (44.7)	49 (56.3)
Abbreviations: D-Kd, DARZALEX + carfilzomib + dexamethasone; FISH, fluorescence in-situ hybridization; ISS, International Staging System; Kd, carfilzomib + dexamethasone.^aGenetic subtypes t(4;14), t(14;16), or del(17p).^bPatients without t(4;14), t(14;16), and del(17p).^cPatients with FISH not done, failed, or of insufficient quantity.^dFive patients in the prior bortezomib/ixazomib subgroups were exposed to ixazomib (D-Kd, n=2; Kd, n=3)

Baseline Characteristics of Patients Either Refractory to Lenalidomide or Bortezomib/Ixazomib¹⁷

Characteristic	Lenalidomide-Refractory		Bortezomib/Ixazomib-Refractory
Characteristic	D-Kd (n=99)	Kd (n=55)	D-Kd (n=100)	Kd (n=55)
Median age (range), years	65.0 (37-83)	64.0 (35-82)	64.0 (33-84)	64.0 (36-77)
ISS stage, n (%)
I	53 (53.5)	27 (49.1)	43 (43.0)	27 (49.1)
II	29 (29.3)	18 (32.7)	29 (29.0)	15 (27.3)
III	17 (17.2)	10 (18.2)	28 (28.0)	13 (23.6)
Unknown	0	0	0	0
Cytogenetic risk by FISH, n (%)
High risk^a	13 (13.1)	8 (14.5)	14 (14.0)	11 (20.0)
Standard risk^b	29 (29.3)	23 (41.8)	33 (33.0)	19 (34.5)
Unknown^c	57 (57.6)	24 (43.6)	53 (53.0)	25 (45.5)
Median prior lines of therapy (range)	2.0 (1-3)	2.0 (1-3)	2.0 (1-3)	2.0 (1-4)
Prior therapies, n (%)
Bortezomib or ixazomib	96 (97.0)	50 (90.9)	100 (100.0)	55 (100.0)
Refractory to bortezomib or ixazomib^d	43 (43.4)	22 (40.0)	100 (100.0)	55 (100.0)
Lenalidomide	99 (100.0)	55 (100.0)	46 (46.0)	29 (52.7)
Refractory to lenalidomide	99 (100.0)	55 (100.0)	43 (43.0)	22 (40.0)
Abbreviations: D-Kd, DARZALEX + carfilzomib + dexamethasone; FISH, fluorescence in-situ hybridization; ISS, International Staging System; Kd, carfilzomib + dexamethasone.^aGenetic subtypes t(4;14), t(14;16), or del(17p).^bPatients without t(4;14), t(14;16), and del(17p).^cPatients with FISH not done, failed, or of insufficient quantity.^dFive patients in the prior bortezomib/ixazomib subgroups were exposed to ixazomib (D-Kd, n=2; Kd, n=3).

Efficacy

At a median follow-up of approximately 17 months, PFS HRs for D-Kd vs Kd ranged from 0.47 to 0.84 across prior treatment subgroups. See Table: Progression-Free Survival in Prior Treatment Subgroups.
The ORR and MRD-negative CR rates were higher for D-Kd vs Kd arms in each subgroup.
ORR and MRD-negative CR data are summarized in Tables: ORR and MRD-Negative CR by Number of Prior Lines of Therapy, ORR and MRD-Negative CR by Prior Lenalidomide Exposure, ORR and MRD-negative CR by Lenalidomide Refractory Status, ORR and MRD-Negative CR by Prior Bortezomib/Ixazomib Exposure, and ORR and MRD-Negative CR by Bortezomib/Ixazomib Refractory Status.

Progression-Free Survival in Prior Treatment Subgroups⁸

Subgroup	D-Kd (n=312)		Kd (n=67)		HR for D-Kd vs Kd (95% CI)	P value (two-sided)
Subgroup	Events/ Patients	Median (95% CI), months	Events/ Patients	Median (95% CI), months	HR for D-Kd vs Kd (95% CI)	P value (two-sided)
All patients	110/312	NE (NE-NE)	68/154	15.8 (12.1-NE)	0.630 (0.464-0.854)
Number of prior lines of therapy						0.7230
1	39/133	NE (NE-NE)	23/67	NE (11.1-NE)	0.679 (0.404-1.142)
≥2	71/179	NE (17.0-NE)	45/87	14.9 (9.3-17.5)	0.605 (0.415-0.881)
Prior lenalidomide exposure						0.3656
Yes	44/123	NE (18.5-NE)	40/74	12.1 (8.4-15.3)	0.529 (0.342-0.818)
No	66/189	NE (NE-NE)	28/80	NE (15.8-NE)	0.708 (0.448-1.120)
Refractory to lenalidomide						0.1772
Yes	34/99	NE (18.5-NE)	32/55	11.1 (7.4-14.9)	0.474 (0.288-0.781)
No	76/213	NE (NE-NE)	36/99	NE (15.7-NE)	0.738 (0.492-1.108)
Prior bortezomib/ixazomib exposure^a						0.9262
Yes	105/289	NE (NE-NE)	63/137	15.3 (11.1-NE)	0.619 (0.452-0.849)
No	5/23	NE (NE-NE)	5/17	NE (11.1-NE)	0.583 (0.165-2.055)
Refractory to bortezomib/ixazomib						0.1510
Yes	48/100	14.2 (9.2-NE)	26/55	14.9 (6.5-NE)	0.840 (0.518-1.361)
No	62/212	NE (NE-NE)	42/99	17.5 (12.3-NE)	0.531 (0.357-0.790)
Abbreviations: CI, confidence interval; D-Kd, DARZALEX + carfilzomib + dexamethasone; HR, hazard ratio; Kd, carfilzomib + dexamethasone; NE, not estimable.^aFive patients in the prior bortezomib/ixazomib subgroups were exposed to ixazomib (D-Kd, n=2; Kd, n=3).

ORR and MRD-Negative CR by Number of Prior Lines of Therapy⁸

Response, %	1 Prior Line of Therapy				≥2 Prior Lines of Therapy
Response, %	D-Kd (n=133)	Kd (n=67)	Odds Ratio (95% CI)	P value	D-Kd (n=179)	Kd (n=87)	Odds Ratio (95% CI)	P value
ORR	90.2	76.1	2.90 (1.30-6.46)	0.0052	79.9	73.6	1.43 (0.78-2.60)	0.1360
MRD-negative CR	16.5	1.5	13.08 (1.72-99.31)	0.0004	9.5	1.1	9.03 (1.18-68.97)	0.0044
Abbreviations: CI, confidence interval; CR, complete response; D-Kd, DARZALEX + carfilzomib + dexamethasone; Kd, carfilzomib + dexamethasone; MRD, minimal residual disease; ORR, overall response rate.

ORR and MRD-Negative CR by Prior Lenalidomide Exposure⁸

Response, %	Prior Lenalidomide Exposure				No Prior Lenalidomide Exposure
Response, %	D-Kd (n=123)	Kd (n=74)	Odds Ratio (95% CI)	P value	D-Kd (n=189)	Kd (n=80)	Odds Ratio (95% CI)	P value
ORR	78.9	74.3	1.29 (0.65-2.54)	0.2434	87.8	75.0	2.41 (1.23-4.69)	0.0055
MRD-negative CR	11.4	0.0	NE (NE-NE)	NE	13.2	2.5	5.95 (1.37-25.74)	0.0034
Abbreviations: CI, confidence interval; CR, complete response; D-Kd, DARZALEX + carfilzomib + dexamethasone; Kd, carfilzomib + dexamethasone; MRD, minimal residual disease; NE, not estimable; ORR, overall response rate.

ORR and MRD-Negative CR by Lenalidomide Refractory Status⁸

Response, %	Lenalidomide Refractory				Lenalidomide Non-refractory
Response, %	D-Kd (n=123)	Kd (n=74)	Odds Ratio (95% CI)	P value	D-Kd (n=189)	Kd (n=80)	Odds Ratio (95% CI)	P value
ORR	79.8	72.7	1.48 (0.69-3.20)	0.1617	86.4	75.8	-	0.0118
MRD-negative CR	13.1	0.0	NE (NE-NE)	NE	12.2	2.0	-	0.0012
Abbreviations: CI, confidence interval; CR, complete response; D-Kd, DARZALEX + carfilzomib + dexamethasone; Kd, carfilzomib + dexamethasone; MRD, minimal residual disease; NE, not estimable; ORR, overall response rate.

ORR and MRD-negative CR by Prior Bortezomib/Ixazomib Exposure⁸

Response, %	Prior Bortezomib/Ixazomib Exposure				No Prior Bortezomib/Ixazomib Exposure
Response, %	D-Kd (n=123)	Kd (n=74)	Odds Ratio (95% CI)	P value	D-Kd (n=189)	Kd (n=80)	Odds Ratio (95% CI)	P value
ORR	83.4	73.7	1.79 (1.10-2.92)	0.0131	95.7	82.4	4.71 (0.45-49.94)	0.1470
MRD-negative CR	11.8	1.5	9.00 (2.13-38.03)	<0.0001	21.7	0.0	NE (NE-NE)	NE
Abbreviations: CI, confidence interval; CR, complete response; D-Kd, DARZALEX + carfilzomib + dexamethasone; Kd, carfilzomib + dexamethasone; MRD, minimal residual disease; NE, not estimable; ORR, overall response rate.

ORR and MRD-negative CR by Bortezomib/Ixazomib Refractory Status⁸

Response, %	Bortezomib/Ixazomib Refractory				Bortezomib/Ixazomib Non-refractory
Response, %	D-Kd (n=123)	Kd (n=74)	Odds Ratio (95% CI)	P value	D-Kd (n=189)	Kd (n=80)	Odds Ratio (95% CI)	P value
ORR	79.0	69.1	1.68 (0.80-3.55)	0.0890	86.8	77.8	-	0.0241
MRD-negative CR	7.0	1.8	4.07 (0.49-33.93)	0.1304	15.1	1.0	-	<0.0001
Abbreviations: CI, confidence interval; CR, complete response; D-Kd, DARZALEX + carfilzomib + dexamethasone; Kd, carfilzomib + dexamethasone; MRD, minimal residual disease; ORR, overall response rate.

Safety

The treatment exposure is summarized in the Table: Treatment Exposure by Subgroup.
Rates of any grade AEs, grade ≥3 AEs, AEs leading to carfilzomib or daratumumab discontinuation, and deaths due to AEs were generally consistent for D-Kd and Kd across the prespecified subgroups; as presented in Tables: Safety Summary by Number of Prior Lines of Therapy and Safety Summary by Refractory Status to Lenalidomide or Bortezomib/Ixazomib.

Treatment Exposure by Subgroup⁸

	1 Prior Line		≥2 Prior Lines		Lenalidomide-Refractory		Bortezomib/ Ixazomib-Refractory
	D-Kd (n=131)	Kd (n=66)	D-Kd (n=117)	Kd (n=87)	D-Kd (n=98)	Kd (n=55)	D-Kd (n=99)	Kd (n=55)
Median duration of treatment, weeks (range)	71.4 (0.3-103.1)	47.0 (1.3-88.4)	65.4 (0.3-97.4)	36.3 (0.3-97.4)	69.3 (0.3-98.3)	34.3 (0.3-97.1)	47.3 (0.3-96.3)	33.3 (1.3-97.3)
Abbreviations: D-Kd, DARZALEX + carfilzomib + dexamethasone; Kd, carfilzomib + dexamethasone.

Safety Summary by Number of Prior Lines of Therapy¹⁷

Characteristic, n (%)	1 Prior Line		≥2 Prior Lines
Characteristic, n (%)	D-Kd (n=131)	Kd (n=66)	D-Kd (n=177)	Kd (n=87)
Any AE	129 (98.5)	63 (95.5)	177 (100.0)	84 (96.6)
Grade ≥3 AE	108 (82.4)	49 (74.2)	145 (81.9)	64 (73.6)
Serious AE	74 (56.5)	31 (47.0)	99 (55.9)	39 (44.8)
Fatal AE	9 (6.9)	4 (6.1)	21 (11.9)	4 (4.6)
Carfilzomib discontinuation due to AEs	30 (22.9)	16 (24.2)	35 (19.8)	17 (19.5)
DARZALEX discontinuation due to AEs	12 (9.2)	0	16 (9.0)	0
Abbreviations: AE, adverse event; D-Kd, DARZALEX + carfilzomib + dexamethasone; Kd, carfilzomib + dexamethasone.

Safety Summary by Refractory Status to Lenalidomide or Bortezomib/Ixazomib¹⁷

Characteristic, n (%)	Lenalidomide-refractory		Bortezomib/Ixazomib-refractory
Characteristic, n (%)	D-Kd (n=98)	Kd (n=55)	D-Kd (n=99)	Kd (n=55)
Any AE	98 (100.0)	53 (96.4)	99 (100.0)	53 (96.4)
Grade ≥3 AE	81 (82.7)	41 (74.5)	80 (80.8)	41 (74.5)
Serious AE	53 (54.1)	26 (47.3)	57 (57.6)	24 (43.6)
Fatal AE	11 (11.2)	4 (7.3)	15 (15.2)	3 (5.5)
Carfilzomib discontinuation due to AEs	19 (19.4)	13 (23.6)	17 (17.2)	6 (10.9)
DARZALEX discontinuation due to AEs	8 (8.2)	0	10 (10.1)	0
Abbreviations: AE, adverse event; D-Kd, DARZALEX + carfilzomib + dexamethasone; Kd, carfilzomib + dexamethasone.

Subgroup Analysis by Prior ASCT

Mateos et al (2021)⁹ presented the efficacy and safety results of D-Kd vs Kd in patients with RRMM with or without prior ASCT subdivided by lenalidomide-refractory and/or lenalidomide-exposed status.

Results

Overall, 269 patients (D-Kd arm, n=194; Kd arm, n=75) received prior ASCT.

Efficacy

At a median follow-up of 27 months, PFS was more favorable in the D-Kd arm vs the Kd arm. See Table: PFS in Patients With and Without Prior ASCT.

PFS in Patients With and Without Prior ASCT⁹

Parameter	Prior ASCT			Without Prior ASCT
Parameter	Overall	LEN-exposed	LEN-refractory	Overall	LEN-exposed	LEN-refractory
PFS HR (95% CI)	0.54 (0.37-0.77)	0.35 (0.20-0.61)	0.30 (0.15-0.59)	0.68 (0.44-1.05)	0.62 (0.33-1.15)	0.62 (0.31-1.22)
2-year PFS rate - D-Kd arm, %	55	57	57	55	53	54
2-year PFS rate - Kd arm, %	31	15	12	44	41	39
Abbreviations: ASCT, autologous stem cell transplantation; CI, confidence interval; D-Kd, DARZALEX + carfilzomib + dexamethasone; HR, hazard ratio; Kd, carfilzomib + dexamethasone; LEN, lenalidomide; PFS, progression-free survival.

Safety

In the D-Kd vs Kd arms:
- Grade ≥3 AEs were reported in 89.6% vs 78.7% of patients with prior ASCT and 82.8% vs 73.1% of patients without prior ASCT, respectively, with consistent rates across lenalidomide subgroups.
- TEAEs leading to treatment discontinuation were reported in 28.6% vs 21.3% of patients with prior ASCT and 25.9% vs 28.2% of patients without prior ASCT, respectively.

Subgroup Analysis in Asian Patients

Suzuki et al (2021)¹⁰ reported the efficacy and safety results of D-Kd vs Kd from a post hoc analysis of the CANDOR study conducted in Asian patients with RRMM.

Results

Patient Characteristics

Baseline characteristics of patients in the Asian subgroup are summarized in the Table: Baseline Patient and Disease Characteristics.

Baseline Patient and Disease Characteristics¹⁰

Characteristic	D-Kd (n=312)	Kd (n=154)	Total (N=66)
Median age (range), years	64 (32.0-80.0)	66 (50.0-77.0)	65 (32.0-80.0)
Male, n (%)	26 (56.5)	12 (60.0)	38 (57.6)
ECOG performance status, n (%)
0 or 1	46 (100.0)	19 (95.0)	65 (98.5)
2	0 (0.0)	1 (5.0)	1 (1.5)
ISS stage^a at baseline, n (%)
I	32 (69.6)	13 (65.0)	45 (68.2)
II	13 (28.3)	3 (15.0)	16 (24.2)
III	1 (2.2)	4 (20.0)	5 (7.6)
Cytogenetics,^b n (%)
High-risk	8 (17.4)	5 (25.0)	13 (19.7)
Standard-risk	15 (32.6)	12 (60.0)	27 (40.9)
Missing or unknown	23 (50.0)	3 (15.0)	26 (39.4)
Number of patients by prior lines of therapy, n (%)
1	24 (52.2)	8 (40.0)	32 (48.5)
2	14 (30.4)	4 (20.0)	18 (27.3)
3	8 (17.4)	8 (40.0)	16 (24.2)
Prior therapies, n (%)
Transplant	31 (67.4)	13 (65.0)	44 (66.7)
PI	40 (87.0)	16 (80.0)	56 (84.8)
IMiD	38 (82.6)	19 (95.0)	57 (86.4)
Bortezomib	40 (87.0)	16 (80.0)	56 (84.8)
Refractory^c to prior bortezomib	13 (28.3)	11 (55.0)	24 (36.4)
Lenalidomide	20 (43.5)	10 (50.0)	30 (45.5)
Refractory^c to prior lenalidomide	16 (34.8)	7 (35.0)	23 (34.8)
PI-including and IMiD-including regimen	33 (71.7)	15 (75.0)	48 (72.7)
Refractory^c to prior PI-including and IMiD- including regimen	10 (21.7)	8 (40.0)	18 (27.3)
Abbreviations: D-Kd, DARZALEX + carfilzomib + dexamethasone; ECOG, Eastern Cooperative Oncology Group; IMiD, immunomodulatory drug; ISS, International Staging System; Kd, carfilzomib + dexamethasone; PI, proteasome inhibitor.^aISS stage: stage 1, beta-2 microglobulin < 3.5 mg/L and albumin ≥ 3.5 g/dL; stage 2, neither stage 1 nor 3; stage 3, beta-2 microglobulin ≥ 5.5 mg/L.^bThe high-risk group consists of the genetic subtypes t(4;14), t(14;16), or deletion 17p and the standard-risk group consists of patients without t(4;14), t(14;16), and deletion 17p.^cPatients were considered refractory to a drug received in prior regimens if any of the following criteria were met: best response to any regimen containing the drug was stable disease or progressive disease, reason for treatment discontinuation was progression in any regimen, date of relapse/progression was after start date and within 60 days after stop date of the drug in any regimen.

Efficacy

HR for progression or death observed in the Asian subgroup (HR, 0.750; 95% CI, 0.259-2.168) was consistent with that observed in the overall CANDOR trial (HR, 0.630; 95% CI, 0.464-0.854). Efficacy outcomes are summarized in the Table: Efficacy Outcomes in the Asian Subgroup.

Efficacy Outcomes in the Asian Subgroup¹⁰

Parameter	D-Kd (n=46)	Kd (n=20)
HR for progression or death (95% CI)	0.750 (0.259-2.168)
Median PFS	NE	NE
ORR, % (95% CI)	93.5 (82.1-98.6)	75.0 (50.9-91.3)
Odds ratio (95% CI)	2.150 (0.321-14.386)
Best overall response, n (%)
CR	21 (45.7)	3 (15.0)
Odds ratio(95% CI)	3.756 (0.940-15.006)
MRD-negative CR^a	11 (23.9)	2 (10.0)
VGPR	18 (39.1)	8 (40.0)
PR	4 (8.7)	4 (20.0)
NR	2 (4.3)	3 (15.0)
PD	1 (2.2)	0 (0.0)
NE	0 (0.0)	2 (10.0)
MRD-negative CR^a rate at 12 months, % (95% CI)	19.6 (9.4-33.9)	5.0 (0.1-24.9)
Odds ratio (95% CI)	3.525 (0.408-30.463)
Mean (SD) time to overall response,^b months	1.2 (0.3)	1.5 (0.7)
Median time to overall response,^b months	1.0	1.1
Mean (SD) time to CR,^c months	8.1 (3.2)	5.6 (2.3)
Median time to CR,^c months	7.7	5.6
Median (95% CI) duration of overall response, months	NE (NE-NE)	NE (7.4-NE)
Abbreviations: CI, confidence interval; CR, complete response; D-Kd, DARZALEX + carfilzomib + dexamethasone; HR, hazard ratio; IMWG-URC, International Myeloma Working Group Uniform Response Criteria; Kd, carfilzomib + dexamethasone; MRD, minimal residual disease; NE, not estimable; NGS, next-generation sequencing; NR, no response (same as stable disease); ORR, overall response rate; PD, progressive disease; PFS, progression-free survival; PR, partial response; SD, standard deviation; VGPR, very good partial response.^aDefined as achievement of CR per IMWG-URC by independent review committee and MRD-negative status as assessed by NGS at a 10^-5 level.^bTime to overall response is defined as the time from randomization to the earliest of CR, VGPR, or PR per IMWG-URC.^cTime to CR is defined as the time from randomization to the earliest of CR per IMWG-URC.

Safety

The safety population included all patients who received at least 1 dose of study treatment. TEAEs are summarized in Tables: Summary of Any Grade (≥20%) or Grade ≥3 (>5%) TEAEs and TEAEs of Interest.
Overview of exposure-adjusted rate of TEAEs in the Asian subgroup is summarized in the Table: Exposure-Adjusted Rate of TEAEs.
Treatment-emergent fatalities were reported in 2 patients in the D-Kd arm due to infections, of which one was due to pneumonia (not related to D-Kd) and the other due to septic shock (related to carfilzomib and DARZALEX).

Summary of Any Grade (≥20%) or Grade ≥3 (>5%) TEAEs¹⁰

Events, n (%)	D-Kd (n=46)		Kd (n=20)
Events, n (%)	Any Grade	Grade ≥3	Any Grade	Grade ≥3
TEAEs	46 (100.0)	44 (95.7)	20 (100.0)	18 (90.0)
Hematologic TEAEs
Thrombocytopenia	27 (58.7)	23 (50.0)	11 (55.0)	6 (30.0)
Anemia	23 (50.0)	15 (32.6)	7 (35.0)	4 (20.0)
Lymphopenia	18 (39.1)	18 (39.1)	9 (45.0)	8 (40.0)
Neutropenia	11 (23.9)	10 (21.7)	4 (20.0)	3 (15.0)
Leukopenia	11 (23.9)	6 (13.0)	3 (15.0)	2 (10.0)
Nonhematologic TEAEs
Hypertension	20 (43.5)	9 (19.6)	7 (35.0)	5 (25.0)
Diarrhea	19 (41.3)	2 (4.3)	8 (40.0)	1 (5.0)
Upper respiratory tract infection	18 (39.1)	1 (2.2)	6 (30.0)	1 (5.0)
Insomnia	16 (34.8)	1 (2.2)	6 (30.0)	1 (5.0)
Nasopharyngitis	14 (30.4)	0 (0.0)	4 (20.0)	1 (5.0)
Nausea	14 (30.4)	NA	1 (5.0)	NA
Fatigue	13 (28.3)	5 (10.9)	3 (15.0)	2 (10.0)
Vomiting	13 (28.3)	NA	2 (10.0)	NA
Decreased appetite	12 (26.1)	1 (2.2)	2 (10.0)	0 (0.0)
Headache	12 (26.1)	NA	6 (30.0)	NA
Pneumonia	11 (23.9)	9 (19.6)	3 (15.0)	2 (10.0)
Pyrexia	11 (23.9)	NA	8 (40.0)	NA
Constipation	8 (17.4)	NA	5 (25.0)	NA
Cataract	6 (13.0)	3 (6.5)	3 (15.0)	2 (10.0)
Dyspnea	6 (13.0)	0 (0.0)	4 (20.0)	1 (5.0)
Hyperglycemia	3 (6.5)	2 (4.3)	3 (15.0)	2 (10.0)
Muscular weakness	2 (4.3)	2 (4.3)	4 (20.0)	0 (0.0)
Cardiac failure congestive	2 (4.3)	0 (0.0)	2 (10.0)	2 (10.0)
Acute kidney injury	1 (2.2)	0 (0.0)	2 (10.0)	2 (10.0)
Abbreviations: D-Kd, DARZALEX + carfilzomib + dexamethasone; Kd, carfilzomib + dexamethasone; NA, not applicable; TEAE, treatment-emergent adverse event.

TEAEs of Interest¹⁰

Events, n (%)	D-Kd (n=46)		Kd (n=20)
Events, n (%)	Any Grade	Grade ≥3	Any Grade	Grade ≥3
TEAEs of interest	46 (100.0)	41.0 (89.1)	19 (95.0)	16 (80.0)
Respiratory tract infections	38 (82.6)	12 (26.1)	11 (55.0)	4 (20.0)
IRR (event on same day as any carfilzomib dosing)	30 (65.2)	6 (13.0)	9 (45.0)	1 (5.0)
Hematopoietic thrombocytopenia	27 (58.7)	24 (52.2)	12 (60.0)	6 (30.0)
Hematopoietic leukopenia	25 (54.3)	25 (54.3)	10 (50.0)	9 (45.0)
Hematopoietic erythropenia	23 (50.0)	15 (32.6)	7 (35.0)	4 (20.0)
Hypertension	21 (45.7)	9 (19.6)	7 (35.0)	5 (25.0)
DARZALEX-related infusion reaction^a	12 (26.1)	0 (0.0)	2 (4.3)	0 (0.0)
Viral infections	9 (19.6)	2 (10.0)	2 (4.3)	0 (0.0)
Peripheral neuropathy	9 (19.6)	NA	1 (5.0)	NA
Dyspnea	9 (19.6)	0 (0.0)	4 (20.0)	1 (5.0)
Cardiac arrhythmias^a	3 (6.5)	1 (2.2)	1 (5.0)	0 (0.0)
Cardiac failure^a	3 (6.5)	0 (0.0)	3 (15.0)	3 (15.0)
Acute renal failure^a	2 (4.3)	0 (0.0)	3 (15.0)	3 (15.0)
Ischemic heart disease^a	0 (0.0)	0 (0.0)	2 (10.0)	1 (5.0)
Abbreviations: D-Kd, DARZALEX + carfilzomib + dexamethasone; IRR, infusion-related reaction; Kd, carfilzomib + dexamethasone; NA, not applicable; TEAE, treatment-emergent adverse event.aEvent on same day or next day of any DARZALEX dosing.

Exposure-Adjusted Rate of TEAEs¹⁰

TEAEs	D-Kd (n=46)			Kd (n=20)			Risk Ratio in D-Kd vs Kd arms
TEAEs	Total number of patients with events (%)	Total patient-years^a	Exposure-adjusted risk estimate (95% CI)^b	Total number of patients with events (%)	Total patient-years^a	Exposure-adjusted risk estimate (95% CI)^b	Risk Ratio in D-Kd vs Kd arms
Grade ≥3	44 (95.7)	5.5	801.55 (596.49-1077.09)	18 (90.0)	3.0	590.17 (371.83-936.72)	1.4
Serious	27 (58.7)	31.2	86.65 (59.42-126.35)	8 (40.0)	13.4	59.83 (29.92-119.63)	1.4
Fatal	2 (4.3)	49.2	4.07 (1.02-16.26)	0 (0.0)	17.2	0.00 (NE-NE)	NE
Abbreviations: CI, confidence interval; D-Kd, DARZALEX + carfilzomib + dexamethasone; Kd, carfilzomib + dexamethasone; NE, not estimable; TEAE, treatment-emergent adverse event. ^aTotal patient-years is the sum of the time to first TEAE for all patients in each treatment group. If a patient has no event, then the entire exposure time to study treatment is considered in the sum. ^bPer 100 patient-years.

PRO Data in Patients in CANDOR Study

Siegel et al (2021)¹¹ reported the results of PRO data collected during treatment.

Results

GHS/QoL completion rates were >81% in both arms for randomized patients who remained on treatment from baseline through Cycle 26.
Overall, the least squares mean estimate (95% CI) of the difference between the two treatment arms was 0.06 (-2.39 to 2.50).
From Cycle 7-26, higher GHS/QoL scores were observed with D-Kd vs Kd and mean differences in GHS/QoL scores increased between treatment arms. See Table: Least Squares Mean Estimate Over Time in Change from Baseline GHS/QoL Score.
The percentage of PRO responders (calculated as the proportion of subjects who had an improvement of ≥10 points in GHS/QoL score from baseline) for D-Kd vs Kd overall was 55.5% vs 43.0%, respectively (OR, 1.65; 95% CI, 1.10-2.45).

Least Squares Mean Estimate Over Time in Change From Baseline GHS/QoL Score¹¹

Time Point	Least Squares Mean Estimate		Mean difference in score (D-Kd vs Kd)	95% CI
Time Point	D-Kd (n=281)	Kd (n=128)	Mean difference in score (D-Kd vs Kd)	95% CI
Cycle 3	0.78	1.35	-0.57	-3.14 to 2.01
Cycle 6	1.34	1.43	-0.10	-2.55 to 2.35
Cycle 9	1.89	1.52	0.37	-2.10 to 2.84
Cycle 12	2.45	1.61	0.84	-1.81 to 3.49
Cycle 15	3.00	1.69	1.31	-1.63 to 4.25
Cycle 18	3.55	1.78	1.78	-1.55 to 5.11
Cycle 21	4.11	1.86	2.25	-1.53 to 6.02
Cycle 24	4.66	1.95	2.72	-1.55 to 6.98
Overall	1.95	1.89	0.06	-2.39 to 2.50
Abbreviations: CI, confidence interval; D-Kd, DARZALEX + carfilzomib + dexamethasone; GHS/QoL, Global Health Status/Quality of Life; Kd, carfilzomib + dexamethasone.

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.

References

Show

1	Usmani SZ, Quach H, Mateos MV, et al. Carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone for the treatment of patients with relapsed or refractory multiple myeloma: results of the randomized phase 3 study CANDOR (NCT03158688). Oral Presentation presented at: 61st American Society of Hematology (ASH) Annual Meeting and Exposition; December 7-10, 2019; Orlando, FL.
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.
3	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.
4	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.
5	Dimopoulos MA, Landgren O, Siegel DS, et al. Carfilzomib, Daratumumab, and Dexamethasone (KdD) Vs Carfilzomib and Dexamethasone (Kd) for Relapsed/Refractory Multiple Myeloma (RRMM) in the Phase 3 Candor Study: Subgroup Analysis According to Renal Functioning. presented at: 65th American Society of Hematology (ASH) Annual Meeting & Exposition; December 9-12, 2023; San Diego, CA.
6	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.
7	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.
8	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.
9	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.
10	Suzuki K, Min C, Kim K, et al. Carfilzomib, dexamethasone, and daratumumab in Asian patients with relapsed or refractory multiple myeloma: post hoc subgroup analysis of the phase 3 CANDOR trial. Int J Hematol. 2021;114(6)(suppl 34410635):653-663.
11	Siegel D, Weisel K, Zahlten-Kumeli A, et al. Health-related quality of life outcomes from the CANDOR study in patients with relapsed or refractory multiple myeloma. Leukemia & Lymphoma. 2021;:1-9.
12	Chari A, Dimopoulos M, Beksac M, et al. Comparison of efficacy outcomes for carfilzomib plus dexamethasone and daratumumab (KdD) versus pomalidomide plus bortezomib and dexamethasone (PVd) and D-Pd in relapsed or refractory multiple myeloma. Poster presented at: 18th International Myeloma Workshop (IMW); September 08-11, 2021; Vienna, Austria.
13	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.
14	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.
15	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.
16	Landgren O, Weisel K, Rosinol L, et al. Supplement to: 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.
17	Quach H, Nooka A, Samoylova O, et al. Supplementary Appendix for: 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.

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