Aim. To analyze major epidemiological parameters of multiple myeloma, i.e. registered incidence, prevalence, mortality, and survival in Novosibirsk, megalopolis in Siberian Federal District. Materials & Methods. The study covered medical records of 335 patients with newly diagnosed multiple myeloma (MM) treated from January 1, 2006 to December 31, 2016 at the Center of Hematology in Novosibirsk. Median age was 67 years (range 30–89), the trial enrolled 218 (65 %) women and 117 (35 %) men. Results. Over the last decade the mean registered MM incidence in Novosibirsk increased by 1.6 times, and MM prevalence increased by 4.9 times. These parameters correspond to 2.4 and 13.8 per 100,000 population per year, respectively, with the linear trend of growth which demonstrates not only the increased number of patients with newly diagnosed MM, but the increased longevity of them. MM incidence and prevalence parameters are significantly higher in women than in men, which most probably can be accounted for by specific administrative factors in the Novosibirsk region. Yearly mortality of MM patients decreased from 28.3 % to 8.2 % with a negative linear trend over the entire analyzed period, which is most likely to be associated with availability of new drugs and transplantation procedures. Conclusion. The obtained epidemiological data will enable to plan the provision of timely and effective care for MM patients and to elaborate a system of judicious allocation of costly equipment and drugs.

Multiple myeloma (MM) is characterized by the uncontrolled proliferation of monoclonal plasma cells and accounts for approximately 10% of all hematologic malignancies. The clinical outcomes of MM can exhibit considerable variability. Variability in both the genetic and epigenetic characteristics of MM undeniably contributes to tumor dynamics. The aim of the present study was to identify biomarkers with the potential to improve the accuracy of prognosis assessment in MM. Initially, miRNA sequencing was conducted on bone marrow (BM) samples from patients with MM. Subsequently, the expression levels of 27 microRNAs (miRNA) and the gene expression levels of ASF1B, CD82B, CRISP3, FN1, MEF2B, PD-L1, PPARγ, TERT, TIMP1, TOP2A, and TP53 were evaluated via real-time reverse transcription polymerase chain reaction in BM samples from patients with MM exhibiting favorable and unfavorable prognoses. Additionally, the analysis involved the bone marrow samples from patients undergoing examinations for non-cancerous blood diseases (NCBD). The findings indicate a statistically significant increase in the expression levels of miRNA-124, -138, -10a, -126, -143, -146b, -20a, -21, -29b, and let-7a and a decrease in the expression level of miRNA-96 in the MM group compared with NCBD (p < 0.05). No statistically significant differences were detected in the expression levels of the selected miRNAs between the unfavorable and favorable prognoses in MM groups. The expression levels of ASF1B, CD82B, and CRISP3 were significantly decreased, while those of FN1, MEF2B, PDL1, PPARγ, and TERT were significantly increased in the MM group compared to the NCBD group (p < 0.05). The MM group with a favorable prognosis demonstrated a statistically significant decline in TIMP1 expression and a significant increase in CD82B and CRISP3 expression compared to the MM group with an unfavorable prognosis (p < 0.05). From an empirical point of view, we have established that the complex biomarker encompassing the CRISP3/TIMP1 expression ratio holds promise as a prognostic marker in MM. From a fundamental point of view, we have demonstrated that the development of MM is rooted in a cascade of complex molecular pathways, demonstrating the interplay of genetic and epigenetic factors.

Introduction. Despite the availability and high effectiveness of modern anticancer drugs used to treat patients with multiple myeloma (MM), most patients inevitably develop disease relapses and refractoriness to the ongoing therapy. The prognosis in patients with relapsed MM and refractoriness to the main classes of anticancer drugs (proteasome inhibitors and immunomodulators) remains poor, and the median overall survival (OS) is only 8 months. Daratumumab is the first fully human IgG1-κ monoclonal antibody that binds with high affinity to the CD38 protein on the surface of myeloma cells, has a direct effect on the tumor, and also has an immunomodulatory mechanism of action. In clinical trials, daratumumab has been shown high effective and safety when used as monotherapy in patients with relapsed and double refractory MM. Aim. To evaluate the effectiveness and safety of daratumumab monotherapy in patients with relapsed/refractory multiple myeloma (RRMM) in real-life clinical practice. Materials and methods. We analyzed 32 patients with RRMM (14 men and 18 women) aged 41–76 years (median 65 years) from two hematological centers in the city of Novosibirsk. In 65.6% of patients, stage IIIA according to Durie-Salmon, stage I–II according to the ISS (in 65.6 and 28.1% of patients, respectively), ECOG performance status 0–1 (in 37.5 and 43.7% of patients, respectively) were diagnosed. Bone-related soft tissue plasmacytomas were recorded in 56.3% of patients, high lactate dehydrogenase activity was noted in 12 (37.5%) patients. The median number of prior lines of therapy was 2 (range 2–4). All patients had previously received proteasome inhibitors (bortezomib) and immunomodulatory agents (lenalidomide). Autologous hematopoietic stem cells transplantation was performed in 34.4% of patients. Double refractory MM was registered in 24 (75%) of 32 patients. The median time from diagnosis of MM to initiation of daratumumab therapy was 73.1 months (range 18–144 months). Daratumumab was administered as monotherapy at a dose of 16 mg/kg intravenously weekly (cycles 1–2), every other week (cycles 3–6), and then monthly. Results. The median duration of therapy with daratumumab was 12.2 months (range 4–22 months). The overall response rate (complete response + very good partial response (vgPR) + partial response (PR)) was 67.7%; vgPR – in 9 (29%) patients, PR – in 12 (38.7%), stable disease (SD) was registered in 19.4% of patients, respectively. The median time to response was 3.5 months (range 2.5–6). The median duration of response was 7.9 months (95% confidence interval (CI) 4.7–11.5). The median progression-free survival (PFS) was 19.1 months (95% CI 15.3–23.6), and the 12- and 18-month PFS were 91% and 50%, respectively. The median OS was not reached, and the 12- and 18-month OS values were 100% and 96.3%, respectively. The depth of the response had a statistically significant effect on the PFS (18-month PFS was 100% in the vgPR and PR subgroups and 81% in the SD subgroup, respectively (χ2 = 19.207, p < 0.001)). Therapy with daratumumab was accompanied with a favorable toxicity profile. In 37.5% of patients, grade 1 and 2 infusion reactions were noted, in 6.2% grade ≥ 3, in one patient, therapy was discontinued due to an infusion reaction of the 3rd degree. Fatigue, upper and lower respiratory tract infections (15.6% and 12.5%, respectively), anemia (15.6%), thrombocytopenia (6.2%), and neutropenia (6.2%) were recorded in 15.6% of patients. Conclusion. Therapy with daratumumab is an effective and safe treatment for RRMM.

Background. Epidemiological studies aggregating data on newly diagnosed multiple myeloma (MM) from real-world clinical practice allow to analyze various clinical and laboratory parameters characterizing general trends in MM diagnosis, treatment outcomes, and life expectancy. Aim. To determine overall survival rates in patients with newly diagnosed MM and to examine factors influencing survival in a population-based study. Materials and methods. A total of 3,184 patients with a newly diagnosed MM from 40 regions of Russia were enrolled in a multicenter prospective study from January 2, 2015, to October 4, 2018. Complete registration of newly diagnosed cases was conducted at each of the 44 participating centers. Information on clinical and laboratory parameters, antitumor therapy regimens administered to patients, including autologous transplantation, was analyzed. Results. The median age of MM patients in Russia was 63 years. It was shown that 39 % of the patients belonged to the older age group 66–90 years, and the percentage of patients under 55 years was 22 %. Only 9 % of patients underwent bone marrow cytogenetic testing. The proportion of patients with kidney damage was 26 %, while 5 % of patients were dialysis dependent. It was shown that 78 % of patients were diagnosed with stage 3 according to Durie–Salmon system, and in 52 % of cases, stage III according to International Staging System was diagnosed. Induction therapy included the use of bortezomib in 94 % of cases, the VCD regimen (bortezomib + dexamethasone + cyclophosphamide) was mainly used, lenalidomide was prescribed extremely rarely – in 1 % of cases. The proportion of patients under 65 years of age who received at least one autologous hematopoietic stem cell transplant was only 18 %. With autologous hematopoietic stem cell transplantation, the median overall survival was 107 months, and in the case of maintenance therapy with lenalidomide, it increased to 129 months. Five-year overall survival of the entire group of patients was 40 %. In a multivariate analysis, independent predictors of worse overall survival were Durie–Salmon stage III, substage B, profound anemia (hemoglobin ≤80 g/L), albumin ≤30 g/L, and hypercalcemia (≥3 mmol/L). Conclusion. This multicenter prospective study of the epidemiological and clinical parameters of newly diagnosed multiple myeloma is unique in Russia in terms of coverage and follow-up duration (over 10 years). Analysis of treatment data for newly diagnosed multiple myeloma identified key issues in diagnosis and treatment.

Background. The prognosis of patients with multiple myeloma (MM) is significantly different depending on the biological characteristics of the tumor substrate, the microenvironment of the bone marrow, as well as factors associated with the patient’s body. Therefore, the search for new reliable and easily identifiable prognostic markers is relevant for the effective management of patients with this disease.The objective of the study was to assess the prognostic value of the study of serum free light chains (FLC) of immunoglobulins κ and λ and their ratio κ / λ FLC in the blood serum of patients with newly diagnosed MM in real clinical practice.Materials and methods. 369 patients with first diagnosed MM (134 men and 235 women) were examined who were hospitalized in the hematology department of the City Clinical Hospital No. 2 Novosibirsk in the period since January 2012 to December 2017. The median age of the patients was 67 (32–82) years. All patients received induction courses of chemotherapy based on bortezomib. The control group consisted of 56 conditionally healthy individuals: 34 women (60.7 %) and 22 (39.3 %) men with a median age of 62 (40–68) years. The concentration of FLC-κ and FLC-λ (mg / L) in blood serum was determined by immunoturbidimetric method on a Hitachi 911 automated biochemical analyzer using the Freelite Human Lambda and Freelite Human Kappa reagent kits (Binding Site, Great Britain).Results. It was found that in patients with MM, the concentration of serum FLC-κ or FLC-λ was statistically significantly higher compared to the control group and varied depending on the type of MM (p 0.001). The diagnostic sensitivity of the quantitative determination of FLC and their ratio for MM was 98.64 %, compared with 94.04 % in a standard immunochemical study. The values of the ratio κ / λ FLC 0.04 or 65, as well as the concentration of FLC-κ and FLC-λ are higher than the median obtained in the whole group (FLC-κ ≥702 mg / L and FLC-λ ≥493.2 mg / L), correlate with known factors of poor prognosis for MM (with a high concentration of β2‑microglobulin (3.5 mg / L) (r = 0.461; p 0.001), plasma cell bone marrow infiltration 60 % (r = 0.420; p 0.001), renal failure (creatinine 177 μmol / L) (r = 0.380; p = 0.002), and also with high lactate dehydrogenase activity (450 U / L) (r = 0.520; p 0.001) and is associated with poor outcomes. The median overall survival in the group of patients with κ / λ FLC 0.04 or 65 was 49 months compared to 76 months in the group with κ / λ FLC 0.04–65 (log-rank p = 0.012).Conclusion. The determination of free FLC in the blood serum of patients with MM can be used to assess the prognosis of their survival. The value of the κ / λ FLC ratio 0.04 or 65 allows us to divide patients with MM into risk groups with significantly different outcomes and can be used to identify patients at high risk who need more aggressive therapy and more detailed monitoring of the response.

Background. An increase in the number of patients with multiple myeloma (MM) necessitates the creation of reliable tools for assessing their somatic status (comorbidity) in order to personalize the optimal treatment regimen that helps to minimize its toxicity, improves survival and patients quality of life.The objective of this study was to modify the MM comorbidity index (MCI) by adding an additional variable reflecting the biological properties of the tumor, and to determine the informativeness of the new scale – a modified MM comorbidity index (M-MCI), to predict the outcome and select personalized therapy in patients with MM in real clinical practice.Materials and methods. From January 2012 to December 2017 the study included 369 patients with newly diagnosed MM (134 men and 235 women) who were hospitalized in the hematology department of the City Clinical Hospital No. 2, Novosibirsk. The median age of the patients was 67 (32–82) years. The prognostic value of concomitant diseases and individual prognostic factors in relation to the overall survival of patients with MM was evaluated.Results. Cox multivariate analysis showed that the most significant predictors of reduced overall survival of patients with MM are impaired renal function (glomerular filtration rate 30 ml / min / 1.73 m2 (according to the CKD-EPI formula), general condition according to the Karnowski scale ≤70 %, chronic obstructive pulmonary disease with moderate (50 % ≤ forced expiratory volume in 1 second 80 %) and severe (30 % ≤ forced expiratory volume in 1 second 50 %) severity of bronchial obstruction and the ratio κ / λ free light chains 0.04 or 65. These factors were combined into a weighted 5‑point scale M-MCI. A comparative analysis of survival depending on the value of the M-MCI allowed us to distribute patients with MM into groups of high (M-MCI 3–4 points) and standard (M-MCI 0–2 points) risk with significantly different indicators of overall survival (median overall survival amounted to 15.5 months in the high and 60 months in the standard risk group; χ2 = 58, p 0.016) and confirm the prognostic value of M-MCI in relation to the outcome of MM.Conclusion. In terms of its prognostic significance in predicting an adverse outcome, the proposed M-MCI scale is superior to its prototype – the MCI. The median overall survival in the high-risk group according to the M-MCI was 15.5 months compared to 20 months according to the MCI; the median overall survival in the group the standard risk was 60 and 50 months, respectively (χ2 = 58 (M-MCI) versus χ2 = 42 (MCI); p 0.001). The advantages of M-MCI are also its more accurate assessment of the physical condition of patients with MM and its simple clinical applicability.