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

In a randomized, open-label, phase 3 study, the CANDOR trial compared carfilzomib, dexamethasone, and daratumumab with carfilzomib and dexamethasone for the treatment of patients with relapsed/refractory multiple myeloma (RRMM) who had undergone 1 to 3 prior lines of therapy. Adding daratumumab to a combination of carfilzomib and dexamethasone (KdD) led to a significant improvement in progression-free survival (PFS) compared with carfilzomib and dexamethasone alone (Kd) (median PFS not reached vs 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 lenalidomide or bortezomib treatment. 

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 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 profile. 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 lenalidomide treatment; and 33% were refractory to bortezomib treatment.

The effects of treatment were generally consistent with KdD versus Kd across subgroups for PFS and ORR. In patients who had previously received ≥2 prior lines of therapy, the median PFS was not reached in the KdD group but was 14.9 months in the Kd group. Furthermore, in patients with prior lenalidomide exposure, the median PFS was not reached in the KdD group, whereas it was 12.1 months in the Kd group. Similarly, in patients with prior bortezomib treatment, the median PFS was not reached in the KdD group, but it was 15.3 months in the Kd group. 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 was 14.2 months in the KdD group, whereas it was not met in the KD group. The effects of treatment were consistent between KdD and Kd across all other subgroups for PFS. 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, with the rates being consistently higher in the KdD group regardless of previous drug exposure or refractory status. The occurrence of grade ≥3 treatment-emergent adverse events in the subgroups by number of and previous lines of therapy was similar to the CANDOR population as a whole.

The subgroup analysis of the CANDOR study suggests that patients administered KdD or KD for the treatment of RRMM have similar efficacy and tolerability irrespective of lenalidomide or bortezomib refractory status or 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.

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