What is the role of the CANDOR (Carfilzomib and Dexamethasone versus Velcade (Bortezomib) and Dexamethasone) trial in relapsed Multiple Myeloma (MM)?

From the Guidelines

The CANDOR trial clearly demonstrates that the combination of carfilzomib, dexamethasone, and daratumumab is a superior treatment option for patients with relapsed or refractory multiple myeloma, with a significant improvement in progression-free survival and overall response rate compared to carfilzomib and dexamethasone alone. This regimen, which consists of carfilzomib 56 mg/m² twice weekly, dexamethasone 40 mg weekly, and daratumumab 16 mg/kg weekly for cycles 1-2, every two weeks for cycles 3-6, and then every four weeks thereafter, has been shown to improve median PFS to approximately 28.6 months versus 15.2 months with the Kd regimen alone 1. The addition of daratumumab to the Kd backbone has been found to increase the overall response rate to about 84% and deepen responses, with higher rates of complete response and minimal residual disease negativity.

Key Points

• The CANDOR trial demonstrated a significant improvement in PFS with the addition of daratumumab to carfilzomib and dexamethasone, with a hazard ratio of 0.59 (95% CI, 0.45-0.78; P<.0001) 1.
• The regimen is particularly valuable for patients who have received 1-3 prior lines of therapy, including those previously exposed to bortezomib and immunomodulatory drugs.
• Common adverse events include thrombocytopenia, anemia, neutropenia, pneumonia, and hypertension, and patients should be monitored for cardiac events due to the risk of cardiovascular complications associated with carfilzomib.

Treatment Considerations

• The combination of carfilzomib, dexamethasone, and daratumumab is a category 1, preferred option for patients with relapsed or refractory MM, according to the NCCN clinical practice guidelines in oncology 1.
• This triplet regimen targets multiple myeloma through complementary mechanisms of proteasome inhibition and anti-CD38 antibody-mediated effects, making it a valuable option for patients with relapsed or refractory disease.

From the FDA Drug Label

CANDOR (NCT03158688) was a randomized, open-label, multicenter trial which evaluated the combination of DARZALEX with twice-weekly carfilzomib and dexamethasone (DKd) versus twice-weekly carfilzomib and dexamethasone (Kd) in patients with relapsed or refractory multiple myeloma who had received at least 1 to 3 prior lines of therapy. Efficacy was evaluated by IRC evaluation of PFS based on the IMWG response criteria. CANDOR demonstrated an improvement in PFS in the DKd arm as compared to the Kd arm; the median PFS had not been reached in the DKd arm and was 15.8 months in the Kd arm (hazard ratio [HR]=0.63; 95% CI: 0.46,0.85; p=0. 0014), representing 37% reduction in the risk of disease progression or death for patients treated with DKd versus Kd.

The CANDOR trial showed that the combination of daratumumab, carfilzomib, and dexamethasone (DKd) significantly improved progression-free survival (PFS) compared to carfilzomib and dexamethasone (Kd) alone in patients with relapsed or refractory multiple myeloma. The median PFS was not reached in the DKd arm, while it was 15.8 months in the Kd arm, representing a 37% reduction in the risk of disease progression or death for patients treated with DKd versus Kd 2.

• Key findings:
  • Median PFS: not reached in DKd arm, 15.8 months in Kd arm
  • Hazard ratio: 0.63 (95% CI: 0.46,0.85)
  • p-value: 0.0014
  • Reduction in risk of disease progression or death: 37%
• Patient population: relapsed or refractory multiple myeloma, 1-3 prior lines of therapy
• Treatment arms: DKd (daratumumab, carfilzomib, dexamethasone) vs Kd (carfilzomib, dexamethasone)

From the Research

CANDOR Trial Overview

• The CANDOR trial is a phase 3 study that evaluated the efficacy and safety of carfilzomib, dexamethasone, and daratumumab (KdD) versus carfilzomib and dexamethasone (Kd) in patients with relapsed or refractory multiple myeloma 3.
• The study found that KdD significantly prolonged progression-free survival compared to Kd, with a median progression-free survival of not reached in the KdD group versus 15.8 months in the Kd group (hazard ratio 0.63; 95% CI 0.46-0.85; p=0.0027) 3.

Efficacy and Safety

• The CANDOR trial demonstrated that the addition of daratumumab to carfilzomib and dexamethasone resulted in a higher overall response rate (84.3% vs 67.7%) and a higher complete response rate (19.1% vs 10.4%) compared to carfilzomib and dexamethasone alone 3.
• The most common grade 3 or 4 adverse events reported in the KdD group were thrombocytopenia, anemia, and neutropenia, which were also reported in the Kd group, but at a lower frequency 3.

Comparison with Other Studies

• The results of the CANDOR trial are consistent with other studies that have evaluated the efficacy and safety of daratumumab in combination with other agents in patients with relapsed or refractory multiple myeloma, such as the study by 4 which found that daratumumab in combination with bortezomib and dexamethasone resulted in significantly longer progression-free survival than bortezomib and dexamethasone alone.
• The CANDOR trial provides further evidence for the use of daratumumab in combination with carfilzomib and dexamethasone as a treatment option for patients with relapsed or refractory multiple myeloma, as discussed in 5.

Treatment Options

• The choice of treatment for patients with relapsed or refractory multiple myeloma should be individualized and based on factors such as the patient's prior treatment history, response to previous therapies, and overall health status, as discussed in 5 and 6.
• The use of daratumumab in combination with other agents, such as carfilzomib and dexamethasone, may be a viable treatment option for patients with relapsed or refractory multiple myeloma, as demonstrated by the CANDOR trial 3.