Combination Therapy for Multiple Myeloma Emerging as Standard of Care

According to data published in The Lancet Oncology, patients with relapsed or refractory multiple myeloma (R/R MM) who were treated with carfilzomib, daratumumab, and dexamethasone (KdD) experienced clear and maintained progression-free survival (PFS) compared with those treated with carfilzomib and dexamethasone (Kd) alone.

These results come from an updated efficacy and safety analysis from the phase 3 CANDOR trial which includes patients aged ≥18 years with R/R MM, who have shown at least a partial response on 1 to 3 previous therapies, and have an Eastern Cooperative Oncology Group performance status of 0 to 2. Included patients were recruited from 102 global medical centers and randomly assigned (2:1) to receive KdD or Kd.

Eligible participants were further stratified by current disease state, previous proteasome inhibitor or anti-CD38 antibody exposure, and number of previous therapies.

The dosing schedule for included participants was as follows:

• “All patients received intravenous infusions of carfilzomib twice per week at 56 mg/m2 (20 mg/m² on days 1 and 2 during cycle 1) on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle.”
• Daratumumab (8 mg/kg) was administered intravenously on days 1 and 2 of cycle 1 and at 16 mg/kg weekly for the remaining doses of the first 2 cycles, then every 2 weeks for 4 cycles (cycles 3 to 6), and every 4 weeks thereafter.
• Patients received 40 mg dexamethasone weekly (20 mg for patients >75 years)."

The analysis was intended to include interim overall survival metrics, but data were not mature at the point of cut-off (June 15, 2020) for final reporting. The primary endpoint was PFS which was assessed by the Onyx Response Computer Algorithm in the intention-to-treat population, with 11 months additional follow-up.

Of 466 enrolled participants, 312 patients received KdD and 154 patients received Kd between June 13, 2017, and June 25, 2018.

For the KdD patient cohort, the median follow-up was was 27.8 months (IQR 25.6-29.5) and PFS was 28.6 months (95% CI 22.7-not estimable [NE]). For the Kd group, the median follow-up was 27 months (13.2-28.6) and PFS was 15.2 months (11.1-19.9) in the Kd group (HR 0.59 [95% CI 0.45-0.78], log-rank P < .0001).

Adverse events were consistent with those reported in the primary analysis. The most common grade 3 or worse treatment-emergent adverse events occurred in 87% of patients in the KdD group, and 76% of the Kd group which included thrombocytopenia (76 [25%] vs 25 [16%], respectively), hypertension (65 [21%] vs 23 [15%]), pneumonia (54 [18%] vs 14 [9%]), and anaemia (53 [17%] vs 23 [15%]).

“A clear, maintained [PFS] benefit of KdD over Kd with longer follow-up was confirmed, making KdD an emerging standard-of-care for patients with [R/R MM],” concluded researchers.

Reference:
Usmani SZ, Quach H, Mateos MV, et al. Carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma (CANDOR): updated outcomes from a randomised, multicentre, open-label, phase 3 study. Lancet Oncol. 2022;23(1):65-76. doi:10.1016/S1470-2045(21)00579-9