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Once-a-Week Treatment With Carfilzomib Shows Benefit Across Patient Subgroups

Allison Inserro
A recent subgroup analysis showed that once-weekly dosing of carfilzomib and dexamethasone reduced the risk of disease progression or death and increased overall response rates in most examined patient subgroups with relapsed and rerefractory multiple myeloma. Multiple myeloma is the third most common hematologic malignancy worldwide, characterized by excessive proliferation of monoclonal plasma cells.
Previous studies have shown that once-a-week dosing of carfilzomib is safe and effective in patients with relapsed and refractory multiple myeloma (RRMM). A new study said that the less-frequent dosing strategy is also safe and effective across patient subgroups.

The subgroup analysis examined once-a-week dosing versus twice-a-week dosing of carfilzomib and dexamethasone by patient characteristics and found, as with earlier studies, that there was a reduced risk of disease progression or death and an increase in the overall response rate (ORR).

Multiple myeloma is the third most common hematologic malignancy worldwide, characterized by excessive proliferation of monoclonal plasma cells.

The subgroup analysis, from the phase 3 ARROW study, looked at age (<65, 65-74, or ≥75 years), renal function (creatinine clearance [CrCl] <50, ≥50 to <80, or ≥80 mL/min), number of prior therapies (2 or 3), and bortezomib-refractory status (yes or no). 

Carfilzomib is a second-generation proteasome inhibitor (PI), while bortezomib is a first-generation PI typically used as a frontline therapy.

Eligibility criteria for the ARROW study included 2 or 3 previous lines of therapy, prior exposure to a PI and an immunomodulatory drug, refractory to most recent therapy, measurable disease (per International Myeloma Working Group consensus criteria), Eastern Cooperative Oncology Group performance status of 0 or 1, and calculated or measured CrCL of ≥30 mL/min. The primary endpoint was progression-free surviva (PFS), and secondary endpoints included ORR, overall safety, and safety.

In the earlier study, once-weekly carfilzomib (70 mg/m2) and dexamethasone (70 mg/m2) improved PFS compared with twice-weekly carfilzomib (27 mg/m2) and dexamethasone (twice-weekly 27 mg/m2) in patients with RRMM (median, 11.2 vs 7.6 months; HR, 0.69; 95% CI, 0.54-0.88; P = .0029). Once-weekly dosing also improved response rates and depth of response.

Compared with twice-weekly dosing, the subgroup analysis showed that once-weekly dosing reduced the risk of progression or death (HR, 0.60-0.85) and increased ORRs in most examined subgroups, consistent with reports in the overall ARROW population.

The safety profiles of receiving 70 mg/m2 across subgroups were also generally consistent with those in the overall population.

The subgroup findings generally show a favorable benefit-risk profile of a once-weekly dose of 70 mg/m2. The authors said that some of the benefit may be due to the higher dose of carfilzomib administered in this treatment arm. In addition, a patient-reported outcomes analysis suggested that the once-a-week dose is convenient and provideds more favorable health-related quality of life than a twice-a-week dose. Adherence may have also been higher, which may have led to improved outcomes.

Regardless of baseline patient and disease characteristics, the analysis supports once-weekly carfilzomib dosing as an appropriate treatment option for patients with RRMM, the researchers said.

Reference

Dimopoulos MA, Niesvizky R, Weisel K, et al.  Once- versus twice-weekly carfilzomib in relapsed and refractory multiple myeloma by select patient characteristics: phase 3 A.R.R.O.W. study subgroup analysis [published online March 9, 2020]. Blood Cancer J. doi: 10.1038/s41408-020-0300-y.

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