Carfilzomib, Daratumumab, and Dexamethasone Combination Yields Superior Outcomes Compared to Carfilzomib and Dexamethasone Among Patients With R/R MM

Final Analysis of the Pivotal Phase 3 CANDOR Trial 

The final analysis of the pivotal phase 3 CANDOR trial, published in Blood Advances, confirmed that combining carfilzomib, daratumumab, and dexamethasone (KdD) yielded superior efficacy outcomes compared to carfilzomib and dexamethasone (Kd) treatment among patients with relapsed/refractory (R/R) multiple myeloma (MM) who had undergone 1 to 3 prior therapies. 

These outcomes were especially significant in specific patient subgroups, including patients refractory to lenalidomide and proteasome inhibitors, and those with high-risk cytogenetics. 

Saad Z Usmani, MD, Memorial Sloan Kettering Cancer Center, New York, New York, and coauthors explain that since patients with MM who relapse are typically refractory to lenalidomide treatment, there is “a need for lenalidomide-sparing treatment options” for this patient population. 

The impetus of the CANDOR trial was to compare outcomes among patients receiving KdD versus Kd, with a primary end point of progression-free survival (PFS). All 466 patients included had an Eastern Cooperative Oncology Group performance status from 0 to 2, had undergone 1 to 3 prior lines of therapy, and experienced a partial or better response to 1 or more prior therapies. This final analysis includes updated efficacy and safety results, focusing on clinically relevant patient subgroups. 

After a median follow-up of 50 months, the median progression-free survival was 28.4 months among patients who received KdD, compared to 15.2 months among patients who received Kd (hazard ratio [HR], 0.64; 95% confidence interval [CI], 0.49 to 0.83). Patients who received the KdD regimen demonstrated significantly higher minimal residual disease (MRD)-negative achievement rates compared to the Kd regimen (28% versus 9%; 95% CI, 2.28 to 7.83). Likewise, the KdD group had superior MRD-negative complete response rates compared to those who received Kd (22% versus 8%; 95% CI, 1.83 to 6.88). The median overall survival in the KdD group was 50.8 months compared to 43.6 months in the Kd group. 

In terms of subgroup analyses, trends toward improved overall survival were observed in particular patient subgroups. These trends were observed in patients who were refractory to lenalidomide (not reached in KdD versus 38.2 months in Kd), patients refractory to proteasome inhibitors (43.2 months in KdD versus 30 months in Kd), and patients with high-risk cytogenetics (34.3 months in KdD versus 17.1 months in Kd). Notably, no new safety signals were identified during this study. 

Dr Usmani et al concluded, “The final analysis of CANDOR confirmed the [progression-free survival] benefit and showed a trend in [overall survival] benefit with KdD vs Kd.”

“These findings reinforce KdD as a standard of care for [R/R] MM, especially in clinically relevant patient subgroups,” they added. 

Source: 

Usmani SZ, Quach H, Mateos MV, et al. Final analysis of carfilzomib, dexamethasone, and daratumumab vs carfilzomib and dexamethasone in the CANDOR study. Blood Adv. Published online: July 18, 2023. doi:10.1182/bloodadvances.2023010026