Purpose: This retrospective study evaluated the efficacy and safety of a weekly carfilzomib, cyclophosphamide, and dexamethasone (KCd) regimen in patients with relapsed or refractory multiple myeloma (RRMM) who had been previously treated with both bortezomib- and lenalidomide-containing regimens. Materials and Methods: We conducted a retrospective analysis of 33 patients with RRMM who received the KCd regimen between March 2020 and February 2024. All patients had prior exposure to both bortezomib and lenalidomide, and the majority (93.9%) were refractory to lenalidomide. Carfilzomib was administered once weekly at 70 mg/m2 (after a step-up dose), along with oral cyclophosphamide and dexamethasone. Treatment response was assessed according to the International Myeloma Working Group criteria, and survival outcomes were analyzed. Results: The overall response rate was 66.7%, including a complete response or better in 15.1% of patients and a very good partial response or better in 42.4%. With a median follow-up of 31.7 months, the median progression-free survival was 13.5 months (95% confidence interval, 11.47 to 15.53), while the median overall survival was not reached. The most common grade ≥ 3 adverse event was neutropenia (15.2%). Non-hematologic grade ≥ 3 toxicities were infrequent and manageable. Conclusion The weekly KCd regimen demonstrated encouraging efficacy and tolerability in a heavily pretreated RRMM population. These findings support its use as a feasible treatment option, particularly in patients refractory to lenalidomide.