CANDOR Study: Subgroup Analysis of Carfilzomib and Dexamethasone with or without Daratumumab in RRMM

The CANDOR trial was a randomized, open-label, phase 3 study in which carfilzomib, dexamethasone, and daratumumab were compared with carfilzomib and dexamethasone (Kd) for the treatment of patients with relapsed/refractory multiple myeloma (RRMM) who had undergone 1 to 3 prior lines of therapy.

When daratumumab was added to a combination of carfilzomib and dexamethasone (KdD), there was a significant improvement in progression-free survival (PFS) compared with Kd alone; median PFS was not reached versus 15.8 months. This subgroup analysis examined the results of CANDOR categorizing subgroups of patients by the number of previous lines of therapy and by prior treatment with lenalidomide or bortezomib.

In CANDOR, 466 patients who had been treated with 1 to 3 previous therapies were randomized 2:1 to receive the combination of KdD or Kd alone. The primary outcome measure was PFS, and the secondary outcome measures included rate of minimal residual disease (MRD) negativity, complete response (CR), overall response rate (ORR) after 12 months, and the safety and tolerability profiles. Among enrolled patients, 43% had undergone 1 prior line of therapy; 57% had ≥2 prior lines of therapy; 42% and 91% had previous treatment with lenalidomide and bortezomib, respectively; 33% were refractory to treatment with lenalidomide; and 33% were refractory to treatment with bortezomib.

The treatment effects were generally consistent with KdD versus Kd across subgroups for PFS and ORR. In patients who had previously received ≥2 prior lines of therapy, median PFS rates were not reached and 14.9 months in the KdD and Kd groups, respectively. Furthermore, in patients with prior exposure to lenalidomide, median PFS was not reached in the KdD group, whereas it was 12.1 months in the Kd group. Similarly, in patients with prior treatment with bortezomib, median PFS was not reached in the KdD group. In the Kd group, however, it was 15.3 months. Among patients who were lenalidomide refractory, median PFS for the KdD therapy group was not reached, and it was 11.1 months for the Kd group. Finally, in patients who were bortezomib refractory, median PFS rates were 14.2 months and not met in the KdD and Kd groups, respectively. The treatment effects for PFS were consistent between KdD and Kd across all other subgroups. The ORR findings ranged from 73% to 90% across all subgroups, and there were no differences in ORR between KdD and Kd among all subgroups. The MRD-negative CR rates ranged from 9.5% to 21.7% in the KdD group versus 0% to 2.5% in the Kd group; the rates were consistently higher in the KdD group regardless of previous drug exposure or refractory status. Similar to the CANDOR population as a whole was the occurrence of grade ≥3 treatment-emergent adverse events in the subgroups by number of and previous lines of therapy.

Analysis based on results from the CANDOR study subgroup suggests that patients administered KdD or Kd for the treatment of RRMM have similar efficacy and tolerability regardless of lenalidomide or bortezomib refractory status or the number of prior lines of therapy.

Reference
Abstract and Poster EP938. EHA 2020. June 12, 2020. Carfilzomib, dexamethasone (KD) and daratumumab versus KD in relapsed or refractory multiple myeloma: subgroup analysis of the CANDOR study by number of prior lines of therapy and prior therapies.