Early Results Suggest That Once-Weekly, High-Dose Carfilzomib Prolongs PFS in Multiple Myeloma

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In the phase 3 ARROW study patients with relapsed/refractory multiple myeloma were randomly assigned to receive carfilzomib 27 mg/m2 twice-weekly or 70 mg/m2 once-weekly
In the phase 3 ARROW study patients with relapsed/refractory multiple myeloma were randomly assigned to receive carfilzomib 27 mg/m2 twice-weekly or 70 mg/m2 once-weekly

Administering carfilzomib once a week significantly improves progression-free survival (PFS) and toxicity compared with twice a week among patients with relapsed/refractory multiple myeloma (RRMM), according to a study published in The Lancet Haematology.1

Carfilzomib twice weekly is currently approved for the treatment of RRMM but is associated with significant burden to both patients and caregivers as treatment must be given via intravenous (IV) infusion over 2 days for 3 weeks per treatment cycle. Findings from the CHAMPION-1/2 study (ClinicalTrials.gov Identifier: NCT01677858) demonstrated that carfilzomib once a week at higher doses could be effective and tolerated by patients with RRMM, but no studies have yet assessed which schedule would lead to better outcomes.

In the phase 3 ARROW study (ClinicalTrials.gov Identifier: NCT02412878), 478 patients with RRMM were randomly assigned to receive carfilzomib 27 mg/m2 twice-weekly or 70 mg/m2 once-weekly; all patients received dexamethasone. Eligible patients received 2 to 3 prior therapies, including proteasome inhibitors and immunomodulatory agents, and were refractory to recent therapies (eg, bortezomib, ixazomib), had measurable disease, and had good performance status.

The median follow-up was 12.6 months and 12.0 months in the once-weekly group and twice-weekly group, respectively.

Results of the pre-specified interim analysis showed that patients in the once-weekly group had a significantly longer median PFS of 11.2 months compared with 7.6 months among those in the twice-weekly arm (hazard ratio [HR], 0.69; 95% CI, 0.54-0.83; P = .0029).

Overall response rate was 62.9% in the once-weekly group compared with 40.8% in the twice-weekly group, and 7% versus 2% of patients reported having complete response or better, respectively.

The rate of grade 3 or worse adverse events (AEs) was higher among patients who received carfilzomib once weekly; AEs occurred at 68% versus 62%, respectively. The most frequently observed AEs included anemia, pneumonia, and thrombocytopenia. Grade 3 or higher cardiac failure occurred less among patients in the once-weekly group (3%) versus twice weekly (4%). Fifty-eight patients in the once-weekly arm and 68 in the twice-weekly arm had died by time of data cutoff.

The authors concluded that these results “show a favourable benefit-risk profile for the once weekly carfilzomib treatment schedule compared with the twice weekly schedule. Furthermore, it is expected that once weekly carfilzomib will provide a more convenient dosing regimen for patients and lead to better adherence to treatment.”

Reference

  1. Moreau P, Mateos MV, Berenson JR, et al. Once weekly versus twice weekly carfilzomib dosing in patients with relapsed and refractory multiple myeloma (A.R.R.O.W.): interim analysis results of a randomised, phase 3 study [published online June 1, 2018]. Lancet Oncol. doi: 10.1016/S1470-2045(18)30354-1

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