Once weekly carfilzomib, promising for refractory myeloma patients

Once weekly carfilzomib appears safe and more effective with a convenient dosing regimen versus the twice-weekly schedule for the treatment of patients with relapsed and refractory multiple myeloma, according to data from a study published in The Lancet Oncology.

Philippe Moreau, Department of Hematology, University Hospital of Nantes, France, and colleagues conducted the phase III ARROW trial to compare progression-free survival in patients with relapsed and refractory multiple myeloma given once weekly carfilzomib or twice weekly carfilzomib.

Twice a week carfilzomib at 27 mg/m² is approved for treatment of relapsed or refractory multiple myeloma. Phase 1/2 CHAMPION-1, the first study exploring once-weekly carfilzomib dosing, established the maximum tolerated dose at 70 mg/m² in combination with dexamethasone.

In the trial, 478 patients with R/R MM from 118 sites were randomized to receive once-weekly or twice-weekly carfilzomib in combination with dexamethasone in 28-day cycles until disease progression or unacceptable toxicity. The patients had previously received 2–3 treatments, including a proteasome inhibitor and an immunomodulatory agent.

Patients in the once-weekly carfilzomib group received 30-minute intravenous infusion on days 1, 8 and 15 of all cycles (20 mg/m² on day 1 in cycle 1, 70 mg/m² thereafter). Those in the twice-weekly carfilzomib group received 10-minute intravenous infusion on days 1, 2, 8, 9, 15 and 16 (20 mg/m² on days 1 and 2 in cycle 1, 27 mg/m²thereafter). Dexamethasone was given at a dosage of 40 mg on days 1, 8 and 15 in all cycles and on day 22 of cycles 1–9 only.

Median carfilzomib exposure was 38 weeks in the once-weekly group and 29.1 weeks in the twice-weekly group, while median dexamethasone exposure was 37.1 weeks and 29.1 weeks, respectively.

Key Findings:

• In an interim analysis of the trial, patients randomized to receive once-weekly carfilzomib (70 mg/m²) plus dexamethasone showed a significant 31 percent improvement in progression-free survival (PFS) vs those who received twice-weekly carfilzomib (27 mg/m²) plus dexamethasone (median, 11.2 months vs 7.6 months; hazard ratio [HR], 0.69; p=0.0029).


• In addition to improvement in the primary endpoint of PFS, patients on once-weekly carfilzomib also had a significantly higher overall response rate [ORR] vs those on the currently approved twice-weekly dosing regimen (62.9 percent vs 40.8 percent).


• Complete response or better was achieved by 7 percent of patients on once-weekly carfilzomib vs 2 percent of those on twice-weekly carfilzomib, while very good partial response or better was achieved by 34 percent vs 13 percent of the patients.


• Compared with the twice-weekly dosing schedule, once-weekly carfilzomib showed a favorable benefit-risk profile and is more convenient.


• Grade ≥3 adverse events occurred in 68 percent of patients on once-weekly carfilzomib vs 62 percent of patients on twice-weekly dosing.


• Frequent grade ≥3 adverse events included anemia (18 percent in both groups), pneumonia (10 percent vs 7 percent), thrombocytopenia (7 percent in both groups), neutropenia (6 percent vs 7 percent), and decreased platelet count (4 percent vs 5 percent).

"Once weekly carfilzomib at 70 mg/m² significantly prolonged progression-free survival versus the twice-weekly schedule. Overall safety was comparable between the groups. Once weekly carfilzomib appears safe and more effective with a convenient dosing regimen versus the twice-weekly schedule for the treatment of patients with relapsed and refractory multiple myeloma," concluded the authors.

For further reference log on to https://doi.org/10.1016/S1470-2045(18)30354-1