SUMMAry

• Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.¹
• The safety data described below reflects exposure to DARZALEX (16 mg/kg) in 2,459 patients with multiple myeloma (MM) including 2,303 patients who received DARZALEX in combination with background regimens and 156 patients who received DARZALEX as monotherapy.¹
• The most frequently reported adverse reactions (incidence ≥20%) were: upper respiratory infection, neutropenia, infusion-related reactions (IRRs), thrombocytopenia, diarrhea, constipation, anemia, peripheral sensory neuropathy, fatigue, peripheral edema, nausea, cough, pyrexia, dyspnea, and asthenia.¹
• The most common (any grade) adverse events (AEs) are presented from the following studies:  
  • CASSIOPEIA for newly diagnosed multiple myeloma (NDMM) patients eligible for autologous stem cell transplant (ASCT).^2-5
  • GRIFFIN for NDMM patients eligible for high-dose therapy (HDT) and ASCT.^6-10 DARZALEX use is not approved by the regulatory agencies for use in combination with bortezomib, lenalidomide, and dexamethasone (VRd) for the treatment of patients with MM. Janssen does not recommend the use of DARZALEX in a manner that is inconsistent with the approved labeling.
  • MAIA and ALCYONE for NDMM patients ineligible for ASCT.^11-13
  • POLLUX, CASTOR, CANDOR, GEN503, and EQUULEUS for relapsed/refractory multiple myeloma (RRMM) patients receiving DARZALEX in combination with background regimens.^14-19
  • GEN501 and SIRIUS for patients with RRMM receiving DARZALEX as monotherapy.^{20, 21}
• Please refer to the following sections of the full Prescribing Information that are relevant to your inquiry: DOSAGE AND ADMINISTRATION, CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS, ADVERSE REACTIONS.

CLINICAL DATA - Newly diagnosed multiple myeloma - TRANSPLANT ELIGIBLE

Combination Treatment with Bortezomib, Thalidomide, and Dexamethasone

CASSIOPEIA is an ongoing, open-label, 2-arm, multicenter, phase 3 study evaluating the safety and efficacy of DARZALEX in combination with bortezomib, thalidomide, and dexamethasone (D-VTd) in patients with NDMM who are eligible for HDT/ASCT.^2,3 Moreau et al (2019)² reported the results from Part 1 of this study. Moreau et al (2021)³ reported results from Part 2 of the CASSIOPEIA study (maintenance treatment) at a median follow-up of 35.4 months.

Study Design/Methods

• Part 1: Patients randomized to 1 of 2 treatment arms (each cycle is 4 weeks):
  • Arm A: Up to 4 cycles of VTd induction therapy followed by ASCT, followed by 2 cycles of VTd consolidation.
  • Arm B: Up to 4 cycles of D-VTd induction therapy, followed by ASCT, followed by 2 cycles of D-VTd consolidation.
• Part 2: Responders rerandomized to 1 of 2 treatment arms:
  • Arm A: Observation
  • Arm B: DARZALEX 16 mg/kg maintenance therapy every 8 weeks for 2 years
• Primary endpoint: Part 1: stringent complete response (sCR) after consolidation therapy assessed at 100 days after ASCT (or immediately after consolidation if
  >100 days); Part 2: progression-free survival (PFS) after second randomization
• Secondary endpoints: Part 1: PFS, time to progression (TTP), proportion of post ASCT/consolidation minimal residual disease (MRD), proportion of post-induction sCR, PFS after next line of therapy (PFS2), and overall survival (OS); Part 2: TTP from second randomization, rate of complete response or better (≥CR), MRD-negativity rates (in patients with ≥CR at a threshold of 10^-5 by next-generation sequencing [NGS]), PFS2, overall response rate (ORR), and OS from second randomization

Safety Results - Part 1  

• AEs are presented in Table: Most Common AEs During Treatment in the Safety Population (CASSIOPEIA Part 1).
• The most common any-grade AEs occurring in ≥20% of patients in either arm (D-VTd [n=536] vs VTd [n=538]) were peripheral sensory neuropathy (59% vs 63%), constipation (51% vs 49%), asthenia (32% vs 29%), peripheral edema (30% vs 28%), nausea (30% vs 24%), neutropenia (29% vs 17%), pyrexia (26% vs 21%), paresthesia (22% vs 20%), and thrombocytopenia (20% vs 14%).
• The most common grade 3/4 AEs occurring in ≥10% of patients (D-VTd vs VTd) were neutropenia (28% vs 15%), lymphopenia (17% vs 10%), stomatitis (13% vs 16%), and thrombocytopenia (11% vs 7%).
• Serious adverse events (SAEs) occurred in 251 (47%) patients in the D-VTd arm and 255 (47%) patients in the VTd arm. The most common SAEs (occurring in ≥3% of patients in either arm) were neutropenia (D-VTd, 4%; VTd, 1%), pneumonia (D-VTd, 4%; VTd, 2%), pyrexia (D-VTd, 3%; VTd, 4%), and pulmonary embolism (D-VTd, 1%; VTd, 4%).

Safety Results - Part 2  

• Any treatment-emergent adverse events (TEAEs) occurred in 95% (n=420) of patients in the DARZALEX monotherapy arm vs 89% (n=394) in the observation arm.
• SAEs occurred in 23% (n=100) patients in the DARZALEX monotherapy arm vs 19% (n=84) in the observation arm.
• SAEs that occurred in >1% of patients in the DARZALEX monotherapy vs observation arms were pneumonia (n=11 [3%] vs n=7 [2%]) and lung infection (n=6 [1%] vs n=7 [2%]), respectively.
• Grade ≥3 TEAEs occurred in 28% (n=122) of patients in the DARZALEX monotherapy arm (who received at least 1 dose) vs 24% (n=108) in the observation arm.
• IRRs occurred in 54.5% (n=115) of patients in the DARZALEX monotherapy arm.
• Two AEs led to death in the DARZALEX monotherapy arm (septic shock and natural killer-cell lymphoblastic lymphoma, n=1 each); both were treatment-related.²²
• Safety data of patients in the DARZALEX monotherapy arm vs observation arm is presented in Table: Most Common AEs (≥10%) in CASSIOPEIA Part 2 Study.

Long-term Follow-up in CASSIOPEIA

Moreau et al (2024)⁴ reported the long-term outcomes of the CASSIOPEIA study after a median follow-up duration of 80.1 months from the first randomization and at a median follow-up duration of 70.6 months from the second randomization.

Safety Results

• A total of 83 vs 139 deaths occurred in the D-VTd vs VTd group, respectively. The causes of death during and after the maintenance phase by induction/consolidation treatment in the maintenance-specific safety population are presented in Table: Causes of Death During and After the Maintenance Phase by Induction/Consolidation Treatment in the Maintenance-Specific Safety Population.
• Second primary malignancies by induction/consolidation treatment in the maintenance-specific safety population are presented in Table: SPMs by Induction/Consolidation Treatment in the Maintenance-Specific Safety Population.

Combination Treatment with Bortezomib, Lenalidomide and Dexamethasone

GRIFFIN (MMY2004; clinical trials.gov identifier NCT02874742)^6-8 is a 2-part, phase 2, randomized, active-controlled US study evaluating the safety and efficacy of DARZALEX in combination with bortezomib, lenalidomide, and dexamethasone (D-VRd) in patients with NDMM eligible for HDT and ASCT. Vorhees et al (2021)²³ reported the final analysis of the safety run-in cohort of this study (Part 1 safety run-in phase final analysis) at a median follow-up of 40.8 months. Voorhees et al (2020)⁸ presented the primary analysis (median follow-up, 13.5 months) and updated analysis of the randomized portion (median follow-up, 22.1 months) of this study. Sborov et al (2022)²⁴ presented the final efficacy and safety results after all patients completed ≥1 year of follow-up after the end of study treatment (median follow-up, 49.6 months). Chari et al (2024)^9,10 reported the final efficacy and safety analysis results of clinically relevant subgroups from the GRIFFIN study at a median follow-up duration of 49.6 months

Study Design/Methods

• Part 1: The safety run-in phase consisted of an induction phase (cycles 1-4; 21-day cycles), followed by ASCT, followed by a consolidation phase (cycles 5-6; 21-day cycles), that was initiated 60-100 days after ASCT, followed by a maintenance phase (cycles 7-32; 28-day cycles).
• Part 2: Following successful completion of the safety run-in phase, in part 2 of the study patients were randomized 1:1 to an induction phase (D-VRd or VRd [cycles 1-4; 21-day cycles]), followed by ASCT, followed by a consolidation phase (D-VRd or VRd [cycles 56; 21-day cycles]), followed by a maintenance phase (DARZALEX + lenalidomide [D-R] or R [cycles 7-32; 28-day cycles]), following the dosing illustrated above, +/- DARZALEX.
• Primary endpoint: sCR (by end of post-ASCT consolidation)
• Secondary endpoints: MRD (10^-5 via NGS), CR, ORR, and very good partial response or better (≥VGPR)

Part 1: Safety Run-in Phase Final Analysis

Vorhees et al (2021)²³ reported the final analysis of the safety run-in cohort of this study (Part 1 safety run-in phase final analysis) at a median follow-up of 40.8 months.

Safety Results

• Eleven patients (68%) experienced an SAE. For the incidences of grade 3/4 TEAEs. See Table: Most Common Grade 3/4 TEAEs (GRIFFIN; Part 1).
• One patient had a TEAE leading to discontinuation of study treatment.
• Fourteen (87.5%) patients experienced any grade infections and 5 (31.3%) patients experienced grade 3/4 infections.
  • During the maintenance phase, 31.3% (n=5) of patients experienced any grade infections, the most common being upper respiratory tract infections. One (6.3%) patient experienced a grade 3/4 infection (pneumonia and bronchitis).
• Grade 1/2 IRRs occurred in 31.3% (n=5) of patients. IRRs included pruritus, chills, flushing, maculo-papular rash, and vascular access site swelling; all occurred during cycle 1 except vascular access site swelling.

Part 2: Randomized Phase

Voorhees et al (2020)⁸ presented the primary analysis (median follow-up, 13.5 months) and updated analysis of the randomized portion (median follow-up, 22.1 months) of this study. Sborov et al (2022)²⁴ presented the final efficacy and safety results after all patients completed ≥1 year of follow-up after the end of study treatment (median
follow-up, 49.6 months).

Safety Results

• In the updated safety and efficacy analysis, any grade infections occurred in 91% of patients in the D-VRd arm and 62% of patients in the VRd arm, the most common being grade 1/2 upper respiratory tract infections; grade 3/4 infections were seen in 23% of patients in the D-VRd arm vs 22% of patients in the VRd arm. See Table: Most Common TEAEs (GRIFFIN; Part 2).
• Pneumonia was reported in 13% of patients in the D-VRd arm and 15% of patients in the VRd arm.

Final Safety Analysis of Maintenance Therapy in GRIFFIN

Sborov et al (2022)²⁴ presented the final efficacy and safety results after all patients completed ≥1 year of follow-up after the end of study treatment (median follow-up,
49.6 months).

• TEAEs leading to treatment discontinuation were similar across treatment arms (D-VRd, 33%; VRd, 31%). One patient in each arm died due to TEAEs unrelated to study treatment.
• Rates of infections leading to treatment discontinuation were similar across treatment arms (D-VRd, 2%; VRd, 3%).
  • The most common infection was upper respiratory tract infection in both arms.
  • In the D-VRd vs VRd arms, Coronavirus Disease 2019 (COVID-19) infections were reported in 5 vs 2 patients.
• TEAEs occurring in ≥30% of patients in the safety population are summarized in Table: Most Common TEAEs (Final Analysis of GRIFFIN).
• A total of 14 patients (D-VRd, n=7; VRd, n=7) died, of whom 9 patients (D-VRd, n=5; VRd, n=4) died due to PD.

Final Analysis in Clinically Relevant Subgroups

Chari et al (2024)^9,10 reported the final efficacy and safety analysis results of clinically relevant subgroups from the GRIFFIN study at a median follow-up duration of 49.6 months.

Study Design/Methods

• This final analysis was conducted after all patients completed ≥1 year of follow-up after concluding study treatment, died, or withdrew.

Results

Safety

• A summary of the most common (>30%) TEAEs in the safety analysis population separated by age <65 years and ≥65 years is provided in Table: Most Common (>30%) any grade TEAEs by Age (<65 years and ≥65 year).
• Among patients aged <65 years (84.7% vs 80.0%) and ≥65 years (88.9% vs 77.8%), the rates of grade 3/4 TEAEs were slightly higher for D-VRd vs VRd.
• The incidence of serious TEAEs was lower in D-VRd vs VRd among patients <65 years, 41.7% vs 56.0% respectively.
• The incidence of serious TEAEs was higher in the D-VRd vs VRd among patients ≥65 years, 59.3% vs 40.7% respectively.
• Two deaths due to TEAE occurred and were considered unrelated to study treatment.
  • <65 years (VRd, n=1; cause unknown)
  • ≥65 years (D-VRd, n=1; pneumonia)

clinical data - newly diagnosed multiple myeloma Transplant-INELIGIBLE

Combination Treatment with Lenalidomide and Dexamethasone

MAIA (MMY3008; clinicaltrials.gov identifier: NCT02252172) is an international, phase 3, randomized, open-label, active-controlled, multicenter study in patients with NDMM not eligible for HDT and ASCT (N=737).^11,25,26 Facon et al (2019)¹¹ presented the pre-specified interim results of this ongoing study with a median follow-up of 28.0 months. Kumar et al (2022)²⁶ presented the results of the updated efficacy and safety analysis (median follow-up, 64.5 months), including updated OS results (median follow-up, 73.6 months), of the MAIA study. Facon et al (2024)¹² presented the results of the updated efficacy and safety analysis of the MAIA study at a median follow-up of 89.3 months (range, 0-102.2).

Study Design/Methods

• Primary endpoint: PFS
• Secondary endpoints: ≥CR rate, ≥VGPR rate, MRD-negativity rate, ORR, OS, PFS2 (time from randomization to disease progression on the next line of therapy or death), safety, sCR, time to next (2nd-line) treatment, time to response, and TTP

Safety Results

• Summary of AEs and second primary cancers (median follow-up, 28.0 months) are summarized in Table: Most Common AEs and Secondary Primary Cancers in the Safety Population (Prespecified Interim Results; MAIA).¹¹
• SAEs: 62.9% for DARZALEX + lenalidomide + dexamethasone (D-Rd); 62.7% for lenalidomide + dexamethasone (Rd)¹¹
• AEs leading to discontinuation: 7.1% for D-Rd; 15.9% for Rd.¹¹
• TEAEs with outcome of death: 6.9% for D-Rd; 6.3% for Rd. Pneumonia was the most common AE that resulted in death (0.5% for D-Rd; 0.8% for Rd).¹¹

Updated Analysis of the MAIA Study

Kumar et al (2022)²⁶ presented the results of the updated efficacy and safety analysis (median follow-up, 64.5 months), including updated OS results (median follow-up, 73.6 months), of the MAIA study. Safety results from this updated analysis are summarized below.

Safety Results

• Summary of TEAEs (median follow-up, 64.5 months) are summarized in Table: Summary of Any Grade (≥30%) and Grade 3/4 (≥20%) TEAEs in the Safety Population (Updated Analysis of MAIA).
  • The grade 3/4 infection rate in the D-Rd vs Rd arm was 42.6% vs 29.6%.
• The most common serious TEAE in both arms was pneumonia (D-Rd, 18.7%; Rd, 10.7%).
• The rate of treatment discontinuation due to TEAEs in the D-Rd vs Rd arm was 14.6% vs 23.8%.

Final Survival Analysis of the MAIA Study

Facon et al (2024)¹² presented the results of the updated efficacy and safety analysis of the MAIA study at a median follow-up of 89.3 months (range, 0-102.2).

Safety and Tolerability Results

• Among the safety population, 78.3% (n=285) of patients in the D-Rd arm and 94.5% (n=345) in the Rd arm discontinued study treatment.
  • Progressive disease was the primary reason for discontinuation in both the D-Rd (32.7%) and Rd arms (38.6%).
  • A lower proportion of patients in the D-Rd (16.5%) and Rd arms (25.8%) discontinued study treatment due to AEs.
• In the D-Rd vs Rd arm, 33% reduction in the risk of death was reported.
  • Deaths were reported for 47.5% (n=173) of patients in the D-Rd arm and 59.7% (n=218) of patients in the Rd arm, mostly due to disease progression. See Table: Summary of Death and Causes of Death in the Safety Population.

Combination Treatment with Bortezomib, Melphalan, and Prednisone

ALCYONE (MMY3007; clinicaltrials.gov identifier: NCT02195479) is a multicenter, randomized, open-label, active-controlled, phase 3 study evaluating the safety and efficacy of DARZALEX when administered in combination with bortezomib, melphalan, and prednisone (D-VMP) compared with administration of VMP alone for the treatment of NDMM in patients (N=706) who were ineligible for high-dose chemotherapy with ASCT.^13,27 Mateos et al (2018)¹³ reported results of a planned interim analysis of this study with a median follow-up of 16.5 months. Mateos et al (2022)²⁷ presented updated safety and efficacy analysis of the ALCYONE study with a median follow-up of 78.8 months.

Study Design/Methods

• Primary endpoint: PFS
• Secondary endpoints: ≥CR rate, ≥VGPR rate, MRD-negativity (10^-5), ORR, and median OS

Safety Results

• Summary of on-treatment AEs (median follow-up, 16.5 months) are summarized in Table: Most Common Any Grade (≥20%) and Grade 3/4 (≥10%) On-Treatment AEs (Safety Population; Planned Interim Analysis in ALCYONE).
• Grade 3/4 infections were more frequent in the D-VMP arm than in the VMP arm (23.1% vs 14.7%), with pneumonia being the most common grade 3/4 infection (11.3% vs 4.0%). In the D-VMP and VMP arms, respectively:
  • Infections, including pneumonia, resolved in 87.9% and 86.5% of patients.
  • Rates of treatment discontinuation because of infections were 0.9% and 1.4%.
  • Infection-related deaths occurred in 5 (1.4%) patients and 4 (1.1%) patients.
• Rates of SAEs were 41.6% in the D-VMP arm and in 32.5% in the VMP arm, with pneumonia being the most common SAE (10.1% and 3.1%, respectively).
• Tumor lysis syndrome occurred in 2 (0.6%) patients in each treatment arm.
• Second primary malignancy occurred in 8 (2.3%) patients in the D-VMP arm and in 9 (2.5%) in the VMP arm.
• Fatal AEs within a month after the last study treatment occurred in 14 (4.0%) patients in the D-VMP arm and in 16 (4.5%) in the VMP arm.

Updated Analysis of the ALCYONE Study

Mateos et al (2022)²⁷ presented updated safety and efficacy analysis of the ALCYONE study with a median follow-up of 78.8 months. Safety results from this updated analysis are summarized below.

Safety Results

• Summary of TEAEs (median follow-up, 78.8 months) are summarized in the Table: Summary of Any Grade (≥15%) and Grade 3/4 (≥5%) TEAEs in the Safety Population (Updated Analysis of ALCYONE).
• In the D-VMP vs VMP arm, grade 3/4 TEAEs were reported in 82.9% vs 77.4% of patients, and grade 3/4 infections were reported in 30.3% vs 15.0% of patients.
• The most common serious TEAE in both treatment arms was pneumonia (D-VMP, 14.7%; VMP, 3.7%).
• The rate of treatment discontinuation due to TEAEs in the D-VMP vs VMP arm was 9.0% vs 9.3%.

clinical data in Relapsed/Refractory Multiple Myeloma

Combination Treatment with Lenalidomide and Dexamethasone

POLLUX (MMY3003; clinicaltrials.gov identifier: NCT02076009) is a phase 3, randomized, open-label, active-controlled, multicenter study that evaluated the safety and efficacy of DRd compared with administration of Rd alone in patients with RRMM (N=569).¹⁶ Dimopoulos et al (2016)¹⁶ reported safety and efficacy results of a prespecified interim analysis of this study (median follow-up, 13.5 months). Dimopoulos et al (2023)²⁸ reported updated results of the POLLUX study, including OS, at a median follow-up of79.7 months.

Study Design/Methods

• Primary endpoint: PFS
• Secondary endpoints: TTP, ORR, ≥VGPR, ≥CR, OS, duration of response (DOR), safety, and MRD

Safety Results

• After a median follow-up of 13.5 months:
  • Any grade infusion reactions were reported in 49% of patients who received DARZALEX. Infusion reactions were mostly grade 1/2 (grade 3 were observed in 5% of patients) and most (92%) occurred during the first infusion. No grade 4 infusion reactions were reported.
  • SAEs were reported in 49% and 42% of patients in the DARZALEX + Rd and Rd arms, respectively.
  • AEs leading to discontinuation were reported in 7% of patients who received D-Rd and 8% in patients who received Rd. The most common of these across both arms were pneumonia, pulmonary embolism, and deterioration of general physical health.
  • AEs leading to death [most commonly (≤1%) acute kidney injury, septic shock, and pneumonia] occurred in 11 (4%) patients in the D-Rd arm and 15 (5%) patients in the Rd arm.

>Six-year Follow-up Update on Safety and Efficacy Outcomes

Dimopoulos et al (2023)²⁸ reported results of the POLLUX study, including OS, at a median follow-up of 79.7 months. Safety results from this updated analysis are summarized below.

Safety Results

• Summary of TEAEs (median follow-up, 79.7 months) are presented in Table: Most common (>15% of patients) and Grade 3/4 (>5% of Patients) TEAEs in the Safety Population (Updated Analysis of POLLUX) and Serious TEAEs and TEAEs Leading to Treatment Discontinuation or Deaths (Updated Analysis of POLLUX).
• Grade 3/4 infections were reported in 44.5% vs 28.1% of patients in the D-Rd vs Rd arms, respectively.
• No deaths because of COVID-19 disease occurred during the study.
• With the longer follow-up, second primary malignancies (cutaneous, invasive, and hematologic) were reported in 40 (14.1%) vs 30 (10.7%) patients in the D-Rd vs Rd arm.

Serious TEAEs and TEAEs Leading to Treatment Discontinuation or Deaths (Updated Analysis of POLLUX)²⁸

Combination Treatment with Bortezomib and Dexamethasone

CASTOR (MMY3004; clinicaltrials.gov identifier: NCT02136134) is an open-label, randomized, multicenter, active-controlled, phase 3 study which evaluated the safety and efficacy of Vd alone compared to D-Vd in patients with RRMM (N=498). Palumbo et al (2016)¹⁸ reported prespecified interim results from this study at a median follow-up of 7.4 months. Sonneveld et al (2023)²⁹ reported presented updated results of the CASTOR study, including OS, at a median follow-up of 72.6 months.

Study Design/Methods

• Primary endpoint: PFS
• Secondary endpoints: time to disease progression, percentage of patients with overall response, DOR, time to response, ≥VGPR, percentage of patients with OS, and MRD

Safety Results

• At a median follow-up of 7.4 months, overall grade 3/4 AEs were experienced more frequently in the D-Vd arm vs the Vd arm (76% vs 62%, respectively).
• IRRs occurred in 45% of patients in the D-Vd arm:
  • IRRs were mostly grade 1/2. No grade 4 reactions were reported.
  • 98% of patients with IRRs experienced the events with the first infusion.
  • Two patients discontinued treatment due to IRRs (bronchospasm in 1 patient; bronchospasm, laryngeal edema, and skin rash in the other patient).
• Treatment was discontinued due to AEs in 7% of D-Vd patients and 9% in Vd patients. The most common AEs (>1% in either arm) leading to discontinuation were peripheral sensory neuropathy and pneumonia.
• A total of 13 (5%) patients in the D-Vd arm and 14 (6%) patients in the Vd arm experienced an AE leading to death.

>Six-year Follow-up Update on Safety and Efficacy Outcomes in CASTOR

Sonneveld et al (2023)²⁹ presented updated results of the CASTOR study, including OS, at a median follow-up of 72.6 months. Safety results from this updated analysis are summarized below.

Safety Results

• Summary of TEAEs (median follow-up, 72.6 months) are presented in Table: Most common (>15% of patients) and Grade 3/4 TEAEs (>5% of patients) in the Safety Population (Updated Analysis of CASTOR).
• Grade 3/4 infections were reported in 72 (29.6%) patients vs 45 (19%) patients in the D-Vd vs Vd arms, respectively.
• TEAEs leading to treatment discontinuations were reported in 10.7% vs 9.3% in the D-Vd vs Vd arms, respectively.
• Deaths due to TEAEs were reported in 17 (7%) patients vs 14 (5.9%) patients in the D-Vd vs Vd arms, respectively.
  • The most frequent TEAEs leading to death were pneumonia (0.8% in both arms) and general physical health deterioration (D-Vd, 0.4%; Vd, 1.3%).
  • Three patients (D-Vd, n=1; Vd, n=2) died during the study due to COVID-19 disease.
• With extended follow-up, second primary malignancies (cutaneous, invasive, and hematologic) were reported in 20 (8.2%) vs 5 (2.2%) patients in the D-Vd vs Vd arm, respectively.

Combination Treatment with Carfilzomib and Dexamethasone

CANDOR (clinicaltrials.gov identifier: NCT03158688) is an ongoing, randomized, open-label, multicenter, phase 3 study evaluating the efficacy and safety of DARZALEX in combination with carfilzomib and dexamethasone (D-Kd) vs carfilzomib and dexamethasone (Kd) in patients with RRMM.¹⁹ Dimopoulos et al (2020)¹⁵ reported the primary results of the CANDOR study at a median follow-up of approximately 17 months. Usmani et al (2023)³⁰ reported the final efficacy and safety results of the CANDOR study after a median follow-up for approximately 50 months.

Study Design/Methods

• Primary endpoint: PFS
• Key secondary endpoints: ORR, MRD (10^-5), and OS

Safety Results

• AEs (median follow-up: D-Kd, 17.2 months; Kd, 17.1 months) are summarized in Tables: Treatment-Emergent Adverse Events (CANDOR), AEs of Interest in CANDOR Study, AEs Leading to Treatment Discontinuation (CANDOR), and Fatal Events (CANDOR).