AIM. To assess the personal experience with the use of anti-CD38 monoclonal antibodies (mAb) for the treatment of relapsed/refractory multiple myeloma (R/R ММ) patients enrolled in the international clinical trials (CT) as well as those treated in real-world clinical practice (RWCP). MATERIALS & METHODS. The present retrospective study includes 63 R/R ММ patients (43 men and 20 women) who received daratumumab or isatuximab monotherapy from 2016 to 2020. The age of patients was 44–80 years; the median time by the start of the therapy to be assessed was 65 years. The analyzed cohort included 24 patients enrolled in the international multi-center CTs (daratumumab IV was administered to 14, daratumumab SC was given to 5, and isatuximab IV was applied in 5 of them). In RWCP, all 39 patients received daratumumab IV. The median number of prior therapy lines in the total cohort was 4 (range 1–10), in the CT group it was 5 (range 2–10), and in the RWCP group it was 4 (range 1–7). Resistance to bortezomib and lenalidomide occurred essentially in all patients under this study. RESULTS. With the follow-up median of 20 months (range 1–62 months), overall response was 50 % in the CT group and 29.3 % in the RWCP group (p = 0.094). The 2-year progression-free survival in these groups of patients was 16.7 and 2.6 %, respectively (p = 0.052). In the CT group, the 2-year overall survival was reported to be 54.2 ± 10.2 % (median 26.5 months) vs. 34.6 ± 7.8 % (median 17 months) in the RWCP group (hazard ratio 0.47; p = 0.022). CONCLUSION. The outcomes of anti-CD38 mAb monotherapy in the RWCP group lag behind those in patients enrolled in the international multi-center CTs. Although approaches to R/R MM treatment continue to be improved, anti-CD38 mAb monotherapy provides a certain treatment niche for heavily pretreated patients with bone marrow hematopoietic exhaustion and cumulative organ toxicity in cases when administration of intensive triplets can cause hypertoxicity. Infusion-related reactions associated with daratumumab or isatuximab mostly occur on their first administration and are not worse than grade 1/2. A switch from IV to SC daratumumab shortens the administration time from a few hours to 3–5 minutes and considerably reduces the incidence of infusion-related reactions.