9th City Clinical Hospital

The aim of the study was to evaluate the relationship between the concentration of interleukin-15 (IL-15) in the blood and coagulation and biochemical parameters in women with COVID-19 at different times of pregnancy and depending on the clinical course of COVID-19. Materials and methods. The study included 60 pregnant women with COVID-19: 14 women in the first trimester, 17 in the second trimester and 29 in the third trimester. The comparison group consisted of 20 pregnant women without clinical and laboratory signs of acute respiratory viral infections. The concentration of IL-15 in the blood serum was determined by enzyme immunoassay. Statistica 10.0 (StatSoft, USA) was used for statistical data processing. The statistically significant error level was considered to be p < 0.05. Results. The main clinical manifestations of COVID-19 in pregnant women are catarrhal respiratory syndrome (93.3 ± 3.23 % of cases), intoxication syndrome (86.7 ± 4.38 % of cases) and neurological manifestations (66.7 ± 6.08 % of cases). Pregnant women with COVID-19 had higher blood levels of IL-15 (p = 0.003). COVID-19 is characterized by a decrease in the level of IL-15 in the blood in the third trimester of gestation compared to the first and second trimesters (p = 0.001; p = 0.013). IL-15 in the blood of SARS-CoV-2-infected pregnant women had a direct correlation with prothrombin time (p = 0.017), thrombin time (p = 0.027) and international normalized ratio (p = 0.039), and an inverse correlation with the level of lymphocytes in the blood (p = 0.009), fibrinogen (p = 0.005), serum iron (p = 0.012) and direct bilirubin (p = 0.008 in mild COVID-19). Factors associated with IL-15 in the blood of pregnant women with COVID-19 are impaired sense of smell and taste (p = 0.043), cough (p = 0.014) and vomiting (p = 0.005). Conclusion. The relationship of IL-15 concentration in the blood with coagulation and biochemical parameters in women with COVID-19 at different stages of pregnancy and depending on the clinical course of COVID-19 was evaluated.

Background and objectives: This phase III study (RI-01-006; FLINTER) was conducted to demonstrate equivalent efficacy of DRL_RI to EU-approved rituximab (MabThera ® ) in patients with previously untreated Stage II–IV, CD20-positive, low-tumor-burden follicular lymphoma (LTB-FL). This study also evaluated safety, immunogenicity, rituximab concentrations, and pharmacodynamics (PD) of DRL_RI compared with MabThera. Design and methods: Previously untreated, stage II–IV, CD20-positive LTB-FL patients ( N = 317) were randomized (1:1) to receive DRL_RI ( n = 162) or MabThera ( n = 155) as intravenous infusions of 375 mg/m² weekly for 4 weeks (induction period), and thereafter every 8 weeks from Week 12 to Week 36 (maintenance treatment), and followed up till Week 52. The primary end point was best overall response rate (BORR) up to Week 28 based on blinded independent central review. Efficacy equivalence was demonstrated if the two-sided 90% confidence interval (CI) for BORR difference was within the prespecified equivalence margin (±17%). Secondary end points included objective and complete responses, duration of response, progression-free survival, overall survival, safety, immunogenicity, mean serum concentrations, and PD. Results: The BORR up to Week 28 was 80.2% versus 79.4% for DRL_RI versus MabThera group; with a difference of 0.89% (90% CI: −6.67 to 8.48; 95% CI: −8.05 to 9.93 within the prespecified margin). Both treatment groups were comparable for all secondary efficacy end points. Treatment-emergent adverse events were reported in 68.6% of patients; safety, immunogenicity, and mean serum concentrations were similar between groups. Peripheral B-cell counts declined below quantifiable limits in most patients, with a median time to B-cell depletion of 6.9 versus 7.0 days for DRL_RI versus MabThera. Conclusion: The study demonstrated efficacy equivalence of DRL_RI to MabThera; with comparable safety, immunogenicity, serum concentrations, and PD between groups. Trial registration: This trial was registered at ClinicalTrials.gov identifier: NCT03976102 and EudraCT (2018-004223-36).

Abstract Background: BCD-217-2/OCTAVA (NCT05732805) is an international, multi-center, randomized, double-blind, placebo-controlled phase III study conducted to access the efficacy and safety of prolgolimab+nurulimab (BCD-217) combination therapy with continued prolgolimab therapy compared to prolgolimab monotherapy as 1st line treatment for patients (pts) with unresectable or metastatic melanoma (un/mM). BCD-217 is a fixed-dose combination of nurulimab (aCTLA-4, 5 mg/ml) and prolgolimab (aPD-1, 15 mg/ml) was recently approved as the 1st line treatment for un/mM in Russia. Here we present the primary analysis of the study. Methods: Pts with unresectable or metastatic cutaneous melanoma (IIIC-IVM1a-c) with treatment- naïve for unresectable/metastatic disease were randomized in 2 treatment arms: combination drug containing nurulimab (1 mg/kg) and prolgolimab (3 mg/kg) at a dose of 0.2 ml/kg Q3W during the first four blinded infusions (nuru+prolgo arm) and prolgo arm received prolgolimab monotherapy at a dose of 3 mg/kg Q3W during the first four blinded infusions. Then both arms received prolgolimab maintenance up to two years. The primary endpoint of the study was progression-free survival (PFS). Results: 271 pts were randomized to nuru+prolgo (n=135) or prolgo monotherapy (n=136) arms. After the median of 15.8 mo follow-up the median PFS (mPFS) was 15.4 (10.3; ND) mo in the nuru+prolgo group and 10.8 (4.7; ND) mo in the prolgo monotherapy group (95% CI, HR 0.68 (0.482; 0.957), iRECIST). The mPFS benefit of nuru+prolgo arm compared to prolgo arm are maintained in RECIST 1.1 assessment: 9.9 mo vs 2.8 mo, respectively. ORR and DCR were also higher in NURU+PROLGO arm. mOS was not reached in both groups (95% CI, HR 0,88, (0.50; 1.55)). 12-mos OS was 84% in each arm. Grade 3-4 treatment-related AE were reported in 16.3% of pts in nuru+prolgo arm compared to 14.0% - prolgo arm. Immune-related AEs (irAE) of all grades were reported in 52.6% of cases in nuru+prolgo arm and 32.4% of cases - in prolgo arm (p 0.0007). Majority of them were mild. The proportion of gr.≥3 irAEs was 13.3% vs 5.9% in nuru+prolgo arm and prolgo arm, respectively (p 0.04). Treatment discontinuation due to AE was reported in 9.6% of cases for nuru+prolgo vs 4.4% of cases for prolgo arm. Conclusions: OCTAVA trial resuts demonstrated that the fixed-dose combination of nurulimab + prolgolimab is significantly more effective than aPD-1 monotherapy without a serious deterioration of the safety profile in patients with metastatic or unresectable cutaneous melanoma as 1st line therapy. Citation Format: Lev Demidov, Igor Samoylenko, Galina Kharkevich, Kristina Orlova, Vladimir Moiseenko, Igor Utyashev, Daniil Stroyakovskiy, Vadim Kozlov, Anastasia Mochalova, Svetlana Demidova, Marina Lyadova, Andrey Kutkovich, Pavel Skopin, Nadezhda Kovalenko, Sufia Safina, Vitaliy Volkov, Yulia Semiletova, Vera Vaschenko, Nikolaiy Kislov, Artem Poltoratsky, Irina Shumskaya, Sergey Kolomiets, Alexander Sobolev, Igor Belogortsev, Svetlana Odintsova, Sameer Rastogi, Timur Andabekov, Anastasia Zimina, Konstantin Penkov, Anna Semenova, Alexey Obukhov, Vasiliy Belyakovsky, Oleg Gladkov, Rakesh Neve, Natalia Falaleeva, Elena Poddubskaya, Amale Vaibhav, Dmitriy Kirtbaya, Yana Chapko, Maria Smagina, Irina Sorokina, Yulia Linkova, Arina Zinkina-Orikhan, Fedor Kriukov, Anton Lutsky, Evgenia Mikhailova. Proved clinical benefit of low-dose anti-CTLA4 + anti-PD-1 immunotherapy versus mono anti-PD-1 therapy in patients unresectable or metastatic melanoma: Phase III OCTAVA trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 653.

Актинический кератоз является наиболее распространенной патологией кожи, характеризуется развитием различной степени выраженности атипии кератиноцитов с риском трансформации в плоскоклеточный рак. В настоящее время с целью проведения дифференциальной диагностики широко используется клинический визуальный осмотр или выполнение биопсии с целью морфологической верификации. На основании литературных данных в статье рассматриваются аспекты и преимущества метода неинвазивного дермоскопического исследования актинического кератоза, который прост в использовании, позволяет с прецизионной точностью проводить дифференциальную диагностику и может активно использоваться врачами-онкологами и дерматовенерологами в ежедневной практике на амбулаторно-поликлиническом уровне. Actinic keratosis is the most prevalence skin lesion, characterized by the variable degree of keratinocyte atypia with the high risk of transformation into squamous cell carcinoma. Currently, clinical and histopathological examination is widely used for differential diagnosis. Based on the literature overview, the article presents the aspects and advantages of noninvasive dermoscopy examination method of actinic keratosis, which is easy to use, allows for precision differential diagnosis and can be actively used by oncologists and dermatovenerologists in daily practice in outpatient service.

High-grade gliomas are the most aggressive form of brain tumors; the average survival rate of patients with this diagnosis does not exceed one and a half years. Tumors occur with a frequency of three cases per 100 thousand population per year. Over the past 35 years, their number has doubled. Malignant gliomas are the third most common cause of death from neoplasms in the group of young people under the age of 35 years. AIM. To study the possibilities of an integrated approach to solving the problem of developing criteria for the characteristics of the clinical course and early progression for patients with glioblastomas, taking into account the growth mechanisms of gliomas. MATERIALS AND METHODS. Archival biopsies of 425 glioblastomas in patients from 18 to 80 years old, operated on at the Republican Scientific and Practical Center of Neurology and Neurosurgery (Minsk). Immunohistochemical markers were used to identify factors responsible for tumor growth rate. The number of vessels was determined, which was counted under the control of monoclonal antibodies to CD34; monoclonal antibodies CD45 (total leukocyte factor), CD8 (T-lymphocytes), CD20 (B-lymphocytes), P53 were used to identify inflammatory infiltration. Comprehensive studies of 6 deceased patients with glioblastoma aged from 18 to 63 years were also used using post-mortem MRI (Russian Research Institute named after Prof. A.L. Polenov). The studied tumors according to the WHO classification belong to glioblastoma NOS, when studies of mutations of the IDH1 and IDH genes were not performed. RESULTS. The time of relapse-free period in patients with glioblastomas, as well as ten-year survival rate, were analyzed, problems arising in the diagnosis and treatment of patients in this category, problems arising during rehabilitation, as well as the legal framework that one has to face when conducting research in neurosurgery were studied, and points related to the risks of surgical interventions. CONCLUSION. To achieve results in increasing the survival rate of patients with glioblastoma, an integrated approach is required to study the heterogeneity of the tumor, develop individual technologies for surgical interventions taking into account the mechanisms of tumor growth and its individual characteristics associated with the histological form in close connection with its molecular genetic characteristics. To reduce the percentage of disability, rehabilitation is required to be as individual as the approach to surgical intervention. By studying the possibilities of cellular technologies in cell cultures, new approaches to the treatment of glioblastoma may be identified. The development of legal support for surgical interventions for patients with highly malignant gliomas is a serious problem for implementation within the framework of the convergence of the legislation of the Republic of Belarus and the Russian Federation on ensuring equal rights of citizens of the Union State.

Background. In an era of breakthroughs in cancer immunotherapy, CheckMate 067 studies declared the combination of PD-1 and CTLA-4 inhibitors a new standard of care for patients with metastatic melanoma (MM). A significant limitation of the widespread use of the combination of ipilimumab and nivolumab in routine clinical practice is the high risk of severe immune-mediated adverse events. Prolgolimab and nurulimab are a combination of fixed doses of original monoclonal antibodies (manufactured by JSC "BIOCAD," Russia) to the PD-1 receptor (prolgolimab) and the CTLA-4 receptor (nurulimab) (3:1 ratio). This paper presents the results of an international, multicenter, double-blind, placebo-controlled, comparative, randomized, phase II OBERTON clinical study to investigate the efficacy and safety of nurulimab + prolgolimab combination therapy with continued prolgolimab therapy compared to prolgolimab alone as first-line therapy in patients with unresectable melanoma (uRM) or MM (NCT03913923). Materials and methods. The study included patients with uRM or MM who were not previously treated for metastatic disease. The patients were randomized into two groups (1:1). Patients in group 1 were treated with a nurulimab (1 mg/kg) and prolgolimab (3 mg/kg) combination at a dose of 0.2 mL/kg (equivalent to 1 mg/kg of nurulimab and 3 mg/kg of prolgolimab) once every 3 weeks during the first 4 blinded infusions. Patients in group 2 received prolgolimab monotherapy at a dose of 3 mg/kg once every 3 weeks during the first 4 blinded infusions. Starting from infusion 5, patients in both groups received open prolgolimab 1 mg/kg once every 2 weeks. The primary endpoint of the study was progression-free survival (PFS). The study is registered on ClinicalTrials.gov under the number NCT05732805 and is currently ongoing, but recruitment of new patients has been completed. Results. One hundred seventeen patients were randomized and received at least one dose of the study therapy. At a median follow-up of 16.79 months, the median PFS was 12.2 (4.9; not achieved) months in the nurulimab + prolgolimab group and 2.8 (1.5; 4.7) months in the prolgolimab monotherapy group (95% confidence interval 0.36-0.90, hazard ratio 0.57). PFS at 24 months was 41% in the nurulimab + prolgolimab group and 25.4% in the prolgolimab monotherapy group. In both groups, the therapy was well tolerated. Grade 3-4 immune-mediated adverse events were reported in 15.5% of patients who received nurulimab + prolgolimab, compared with 1.7% of those who received prolgolimab alone. The most frequent grade 3-4 treatment-related adverse events in both treatment groups were increased alanine aminotransferase and aspartate aminotransferase and asthenia. Overall, the safety profile was favorable, as expected for the class of immune checkpoint inhibitors, anti-CTLA-4, and anti-PD-1 monoclonal antibodies. Discussion. The results demonstrate a favorable safety profile in both the nurulimab + prolgolimab combination and prolgolimab monotherapy groups as the first-line treatment for uRM or MM. The assessment of the primary endpoint, PFS, showed the benefit of combination immunotherapy followed by switching to prolgolimab compared to prolgolimab alone. Conclusion. Combination immunotherapy with the CTLA-4 inhibitor nurulimab and the PD-1 inhibitor prolgolimab, available as a combination of solutions of two drugs in a single vial, with a further switch to monotherapy with prolgolimab, can fill an important niche in the treatment of patients with uRM or MM. Confirmation of the obtained data on the efficacy and safety of the combined regimen of nurulimab + prolgolimab in comparison with PD-1 inhibitor monotherapy is expected from the ongoing phase III BCD-217-2 OCTAVA study (NCT05732805).

Abstract AimWe conducted a meta-analysis on the effectiveness of sodium-glucose co-transporter 2 (SGLT2) inhibitors in heart failure (HF) patients with preserved (HFpEF) and reduced (HFrEF) ejection fraction.MethodsA comprehensive search of several databases for placebo-controlled randomised controlled trials of SGLT2 inhibitors from inception to September 30 2022, limited to English language and excluding animal studies, was conducted. The databases included Medline, Scopus, Cochrane Central, and ClinicalTrials.gov. Randomised controlled studies were chosen if they included HF patients and reported at least one of the predetermined outcomes. Hazard ratios (HRs) or risk ratios were pooled together with the appropriate 95% confidence intervals using a random-effect model. Fourteen trials met the inclusion criteria, with 42 409 HF patients participating (N = 21 678 in the SGLT2 inhibitor arms and N = 20 731 in the placebo arms).ResultsSGLT2 inhibitors significantly reduced the composite of HF hospitalisation or cardiovascular death [HR: 0.75 (0.71–0.79);P< 0.001;I2= 0%], total hospitalisations for heart failure [HR: 0.70 (0.66– 0.75);P< 0.001;I2= 0%], and reduced the occurrence of cardiovascular death [HR: 0.86 (0.81–0.92);P< 0.001;I2= 43%]. Sub-group analysis was conducted based on HF status at baseline, EF, diabetes status at baseline, and sex. SGLT2 inhibitors significantly reduced the composite heart failure hospitalisation and cardiovascular death for all the subgroups except for patients with HFpEF at baseline [HR: 0.87 (0.74– 1.03);P= 0.11;I2= 60%] and no diabetes status at baseline [HR: 0.92 (0.73–1.16);P= 0.50;I2= 78%].ConclusionsIn patients with HF, SGLT2 inhibitors may significantly improve clinical outcomes, including all-cause and cardiovascular mortality. In this meta-analysis, SGLT2 inhibitors did not show a reduction in composite heart failure in patients with heart failure with preserved ejection fraction at baseline.

ABSTRACTPurposeThe purpose of this clinical study is to evaluate safety and efficacy of ELENAGEN, a novel anticancer therapeutics (plasmid DNA encoding p62/SQSTM1) protein, as an adjuvant to chemotherapy with Gemcitabin (GEM) in patients with advanced platinum-resistant ovarian cancer.Patients and MethodsThis was a prospective randomized multi-center study with two arms. Gemcitabine 1000 mg/m2days 1,8 every 3 weeks) was administered in both arms: In the Chemo arm (n = 20) GEM was the only treatment, and in the ELENAGEN arm (n = 20) GEM was supplemented with ELENAGEN (2.5 mg i.m. weekly). The primary endpoint was progression-free survival (PFS), and the secondary endpoint was safety. Antitumor activity was assessed by RECIST 1.1 criteria. Safety was assessed on the basis of adverse events (AEs) and serious AEs (SAEs) according to NCI CTCAE version 5.0.ResultsTo data cut-off, the median follow-up was 13.8 months. There were no SAE -related to ELENAGEN treatment. The median progression-free survival (PFS) was 2.8 and 7.2 mo in Chemo and ELENAGEN arms respectively (p Log-Rank = 0.03). Noteworthy, at the time of cut-off, 9 patients (45%) in Elenagen arm did not progress with the longest PFS recorded so far is 24 months. Subgroup analysis of patients in both arms demonstrated high efficacy of Elenagen in the patients with worse prognosis: high pretreatment levels of CA125, progression after only one line of chemotherapy, and peritoneal effusion.ConclusionsAddition of ELENAGEN to Gemcitabine is effective in patients with ovarian cancer, including those with a worse prognosis.

e17540 Background: We recently reported on the efficacy of the p62/SQTM1-encoding plasmid in patients with advanced, recurrent platinum-resistant ovarian cancer (PROC) receiving gemcitabine chemotherapy. Here we analyze the effects of baseline prognostic factors on efficacy. Methods: A prospective multicenter randomized study took place between 01/2020 and 08/2023. Cohort A (n=20) consisted of Gemcitabine 1000 mg/m2 days 1,8 every 3 weeks and Cohort B (n=20) consisted of Gemcitabine (Gem) 1000 mg/m2 days 1,8 every 3 weeks plus p62-plasmid 2.5 mg i.m. weekly. We stratified the patients into subgroups according to their baseline CA-125 level (normal vs high), number of lines of chemo (1 vs 2-3) received by a platinum-sensitive ovarian cancer (PSOC) patient before they became PROC, platinum-free interval (PFI) (up to 3 mo vs more than 3 mo), and presence or absence of peritoneal effusion. Cox proportional hazards regression analysis was utilized to determine effect of progression free survival (PFS). Results: The median follow-up was 13.8 months (mos). The median PFS was 2.8 mos in Gem (Arm A) and 7.2 mos in Gem + Plasmid (Arm B) respectively (p = 0.03). The overall response rate (ORR) by RESIST 1.1 was higher in the Gem +Plasmid arm: partial response (PR) - 5.0% and 20.0%, stable disease (SD) - 40.0% and 60.0%, and disease control rate 41.2 and 80% in Chemo and Plasmid arms respectively). In cohort A, all patients have progressed, whereas in Cohort B (Gem +Plasmid) 9 patients (45%) remained progression-free with the longest duration of response being 30 mo. Overall survival cannot be assessed yet. Analyzing prognostic factors with Cox Proportional Hazards Regression Analysis identified that the following factors increase p62 sensitivity: initial high CA-125 level PFS 2.5 and 6.5 (p = 0.01) in Arm A vs B, 1 line chemo vs 2 or 3 lines for PSOC, PFS 2.3 and 7.1 (p = 0.008) in Arm A vs B, and presence of peritoneal effusion PFS 2.4 and 7.6 (p = 0.008) in Arm A vs B (Table ). Conclusions: We observed maximal effect on PFS when combining the p62-encoding plasmid with Gem in the patients with the most dismal prognosis PROC: rapid progression (relapse as PROC after the first line of treatment and/or short PFI), in patients with an initial high level of CA-125, and/or pleural effusion. [Table: see text]