The phase 3 A.R.R.O.W. study demonstrated that treatment with once-weekly carfilzomib (70 mg/m2) and dexamethasone (once-weekly Kd70 mg/m2) improved progression-free survival compared with twice-weekly carfilzomib (27 mg/m2) and dexamethasone (twice-weekly Kd27 mg/m2) in patients with relapsed and refractory multiple myeloma (RRMM; median, 11.2 versus 7.6 months; hazard ratio [HR] = 0.69; 95% confidence interval, 0.54-0.88; P = 0.0029). Once-weekly dosing also improved response rates and depth of response. We performed a subgroup analysis from A.R.R.O.W. according to age (<65, 65-74, or ≥75 years), renal function (creatinine clearance <50, ≥50-<80, or ≥80 mL/min), number of prior therapies (2 or 3), and bortezomib-refractory status (yes or no). Compared with twice-weekly Kd27 mg/m2, once-weekly Kd70 mg/m2 reduced the risk of progression or death (HR = 0.60-0.85) and increased overall response rates in nearly all the examined subgroups, consistent with reports in the overall A.R.R.O.W. population. The safety profiles of once-weekly Kd70 mg/m2 across subgroups were also generally consistent with those in the overall population. Findings from this subgroup analysis generally demonstrate a favorable benefit-risk profile of once-weekly Kd70 mg/m2, further supporting once-weekly carfilzomib dosing as an appropriate treatment option for patients with RRMM, regardless of baseline patient and disease characteristics.