Objective To investigate the efficacy and safety of carfilzomib + dexamethasone + pomalidomide in the treatment of relapsed and refractory multiple myeloma (RRMM). Methods A retrospective analysis of the medical records of 80 patients with RRMM admitted to our hospital from January 2020 to January 2024 was conducted. Patients admitted and treated from January 2020 to January 2022, totaling 38 cases, were included in the control group. Patients admitted and treated from February 2022 to January 2024, totaling 42 cases, were included in the observation group. The control group received treatment with dexamethasone + lenalidomide + bortezomib, while the observation group received treatment with dexamethasone + lenalidomide + carfilzomib. The clinical efficacy, serum protein markers ［serum M protein, hemoglobin, β2-microglobulin (β2-MG)］ and tumor load indicators ［serum free light chain κ/λ ratio, lactate dehydrogenase (LDH)］ before and after treatment and occurrence of adverse reactions were compared between groups, and the progression-free survival and overall survival status of the two groups were analyzed by Kaplan-Meier curve. Results After treatment, the total remission rate in observation group (71.43%) was notably higher compared to that in the control group (44.74%) (P<0.05). Serum protein marker and tumor load indicator levels in the two groups were significantly lower than their pre-treatment levels. Additionally, the levels in the observation group were notably lower (P<0.05). The hemoglobin level was significantly risen compared with that before treatment, and the level was significantly higher in observation group (P<0.05). No statistically significant differences were observed between the two groups in terms of blood-related and non-blood-related adverse reactions (P>0.05). After 18 months of follow-up, after adjusting for confounding factors such as age, number of previous treatment lines, course of disease and staging, the median progression-free survival time and overall survival time with 14 months and 18 months in observation group were significantly longer than 12 months and 14 months in control group(progression-free survival time: Log rank χ2=7.345, HR=0.712, 95%CI: 0.583-0.874; overall survival time Log rank χ2=18.798, HR=0.627, 95%CI:0.504-0.779, both P<0.001). Conclusion The application of carfilzomib combined with dexamethasone and lenalidomide as a treatment regimen for patients with RRMM shows a good therapeutic effect. It not only significantly improves bone marrow function and promotes the reduction of disease activity, but also effectively relieves the tumor burden. It is helpful to prolong the life of patients, and this regimen is well tolerated by patients