Once-weekly carfilzomib promising in relapsed/refractory multiple myeloma
Once-week carfilzomib may represent a more convenient treatment option for patients with relapsed/refractory multiple myeloma (R/R MM), according to data from the phase III ARROW trial.
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). [Mateos MV, et al, ASCO 2018, abstract 8000; Lancet Oncol 2018, doi: 10.1016/S1470-2045(18)30354-1]
“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; p<0.0001],” reported investigator Dr Maria-Victoria Mateos of the University Hospital of Salamanca, Spain.
“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,” she continued. “The median duration of overall response was 15 months vs 13.8 months.”
Overall survival data were not yet mature at the time of the interim analysis.
“Compared with the twice-weekly dosing schedule, once-weekly carfilzomib showed a favourable benefit-risk profile and is more convenient,” said Mateos. “The safety findings were consistent with the known safety profile of carfilzomib, with no new risks identified.”
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 anaemia (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).
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/m2 thereafter). 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.