INTRODUCTION Bortezomib was the first proteasome inhibitor approved for the therapy of multiple myeloma (MM). Currently, VMP (bortezomib, melphalan, prednisone) is one of the standard regimens recommended as the first‑line therapy for patients with MM ineligible for high‑dose chemotherapy (HDT) with autologous stem‑cell transplantation (auto‑SCT). OBJECTIVES Participants of clinical trials are highly selected populations; therefore, the aim of this study was to present observations from real practice that might provide important information for practitioners. PATIENTS AND METHODS We retrospectively analyzed the data on the efficacy and safety of bortezomib‑based regimens in 154 patients with newly diagnosed MM ineligible for HDT with auto‑SCT (median age, 73 years; range, 39-89 years) with particular attention to the effect of age, performance status, and concomitant diseases. RESULTS Patients aged 75 years or older constituted 53.2% of the study cohort. Performance status was impaired in 34.4% of the patients, according to the Eastern Cooperative Oncology Group scale. Comorbidities were reported in 83.8% of the patients (mainly arterial hypertension and atherosclerotic vascular disease). A total of 798 courses of bortezomib‑based regimens (mainly VMP, 86%) were administered. The overall response rate was 81.7%, including 12.7% for complete response and 29.6% for very good partial response. The median progression‑free survival (PFS) and event‑free survival were 17.3 and 7.1 months, respectively. The impaired performance status and age of 75 or older were negative predictors of PFS. The most common severe adverse events were neuropathy (19.4%), infections (19.2%), and neutropenia (14.9%). CONCLUSIONS Bortezomib‑based regimens are effective and well tolerated in the first‑line therapy of elderly patients with MM and comorbidities, with advanced disease, and light chain MM. A more detailed assessment of patients' frailty is needed to increase the efficacy of treatment.