Objective To investigate the clinical efficacy of bortezomib,dexamethasone combined with cyclophosphamide in the treatment of myeloma and the effect on the occurrence of adverse reactions in patients. Methods The subjects were 60 myeloma patients admitted to our hospital from January 2016 to December 2020, and they were randomly divided into study group 1 (n=20), study group 2 (n=20) and control group (n=20). The control group received bortezomib combined with thalidomide and dexamethasone chemotherapy, the study group 1 received bortezomib combined with cyclophosphamide and dexamethasone chemotherapy, and the study group 2 received bortezomib combined with lenalidomide and dexamethasone chemotherapy. The therapeutic efficacy, the changes of immune function,serum factors and bone metabolism factors were compared among the three groups. Results The effective rate of control group was 85.0%, which was lower than those of study group 1 and study group 2 (P＜0.05). There was no significant difference of immune function among the three groups before treatment (P＞0.05), which of the control group after treatment was worse than that of the study groups (P＜0.05). There were no significant differences in the levels of related serum factors among the three groups before treatment (P＞0.05),which in the control group after treatment was higher than those in the study group 1 and study group 2 (P＜0.05). After treatment, the changes of bone metabolic factors in control group were worse than those in study group 1 and study group 2 (P＜0.05). Conclusion Bortezomib, dexamethasone combined with cyclophosphamide in the treatment of myeloma had ideal effect, and the incidence of adverse drug reaction was reduced, the quality of life of patients was improved, which can be popularized in clinical application.