Leningrad Regional Cancer Center

TPS583 Background: Lenvatinib plus pembrolizumab (Len+P) is an established first-line regimen for metastatic clear cell renal cell carcinoma (mRCC). In the CLEAR study, patients with low tumor burden derived substantial benefit; however, ~20% achieved only stable disease (SD) as best response. In the VOLGA study, outcomes were improved when even a single lesion was irradiated during targeted therapy. We hypothesize that adding stereotactic body radiotherapy (SBRT) to multiple lesions in patients with SD during Len+P therapy will increase the objective response rate (ORR) and potentially improve overall survival (OS). Methods: LASER is a randomized, multicenter, phase 2 study. Eligible patients must have histologically confirmed mRCC, sum of target lesion diameters ≥7 cm, ECOG PS 0–2, and no prior systemic therapy for metastatic disease. All patients receive 12 weeks of induction therapy with Len (20 mg daily) plus P (200 mg Q3W). Imaging is performed per RECIST v1.1 to classify response as complete/partial response, SD, or progression. Patients with SD are randomized 1:1 to: (1) Len+P+SBRT or (2) Len+P alone. In the SBRT arm, up to 3 lesions are selected for irradiation by a multidisciplinary team. The primary endpoint is ORR of non-irradiated lesions after randomization, assessed every 12 weeks per RECIST v1.1. Secondary endpoints include progression-free survival (PFS), OS, response from irradiated lesions, and safety. The study is powered to detect an increase in ORR from 15% (control) to 50% (SBRT arm), with α = 0.05 and 80% power, requiring 27 patients per arm (54 randomized). Total planned enrollment is 150 patients to account for the proportion achieving SD following induction. Clinical trial information: KCRB-092025/2.

Background. A Russian phase IV observational study was initiated to evaluate the efficacy and safety of lenvatinib with pembrolizumab (Len-Pembro) in patients with advanced renal cell carcinoma (RCC) receiving therapy in real-world practice. This article is based on the results of the third analysis conducted with a median follow-up of 23.1 months and reflects data on the efficacy and safety of Len-Pembro in Russian patients. Aim. To evaluate the real-world efficacy and safety of Len-Pembro in patients with advanced RCC with a median follow-up increased to 23.1 months. The primary outcome of the study was progression-free survival (PFS), the secondary outcomes included overall survival (OS), progression-free survival on next-line therapy (PFS2), objective response rate (ORR), duration of response, as well as safety. Materials and methods. The study included data from 165 patients with verified advanced RCC who received Len-Pembro at 36 centers in the Russian Federation from February 05, 2018 to July 30, 2025. The median age was 60 (20–76) years, and 70.3% of the participants were male. Most patients (74.6%) presented with Karnofsky performance score of ≥80%, metachronous metastases (50.9%) of clear cell RCC (93.3%) in 1 organ (75.2%), and had not received any anticancer treatment (91.0%). The IMDC favorable prognosis group included 40 (24.2%), intermediate – 92 (55.8%), and unfavorable prognosis – 33 (20.0%) patients. The median follow-up reached 23.1 (0.5–72.9) months. A total of 110 (66.7%) patients completed Len-Pembro therapy, and 51 (30.9%) patients received next-line treatment. Results. Median PFS reached 25.8 (95% confidence interval – CI 17.0–34.5) months, 23-month PFS – 52.6%; median OS was 39.9 (95% CI 26.9–52.8) months, 23-month OS – 73.1%; median PFS2 was 33.2 (95% CI 23.4–41.1) months, 23-month PFS2 – 66.9%. The ORR was 49.1%, including 3.0% of complete responses, and the disease control rate was 89.1%. The median duration of response reached 29.7 (95% CI 24.9–34.6) months. The incidence of any adverse events (AEs) was 78.8%, severe AEs occurred in 29.1%, fatal AES – in 1.2%, immune-related AEs – 17.0%, severe immune-related AEs – 6.7%. Conclusion. In real-world practice, with increased follow-up duration, the values of PFS, OS, and PFS2 were comparable to those obtained in the registrational study, with a lower ORR and a satisfactory safety profile of the combination of Len-Pembro in advanced RCC.

Purpose: to study the clinical efficacy and safety of phacovitrectomy (PhEV) in the surgical treatment of rhegmatogenous retinal detachment (RRD). Materials and methods. We observed 146 patients (146 eyes) aged 34 to 77 years (mean age 56.4 ± 1.9 years). The inclusion criteria for patients in the study were: total RRD, complicated proliferative vitreoretinopathy (PVR) stages “B-C”, the presence of a native lens, no history of previous surgeries for RRD. All patients were divided into two groups equal in age, RRD localization and severity of PVR: the main group (MG, 74 patients, 74 eyes) — eyes that underwent PhEV; the control group (CG, 72 patients, 72 eyes) — who underwent only vitrectomy (VE). Comparative assessment of surgical safety was performed based on the incidence of intraoperative, early (up to 10 days) and late (1–3 months) postoperative complications. Comparative assessment of clinical efficacy of surgical intervention was performed based on the following parameters: anatomical retinal attachment, development of cystoid macular edema, and formation of epiretinal membrane. Results and discussion. The developed PhEV technique provides a higher level of safety and clinical efficacy of surgical treatment in patients with RRD, which is proven (compared to the group of patients who underwent only VE) by a decrease (on average, by 13.7, 4.1, 10.3 %) in the probability of intraoperative, early and late postoperative complications, as well as the incidence of cystoid macular edema and epiretinal membrane (p < 0.01). The main factor in intraoperative complications is a decrease (up to loss) in intraoperative visualization associated with the development of transient lens opacity. An increase in the incidence of cataract development in the CG during dynamic observation was noted from 16.7 % with an observation period of 10 days to 27.8 % with an observation period of 1–3 months. An almost identical and high (94.4–96.0 %) level of probability of anatomical reattachment of the retina was determined in patients of both groups. The higher level of safety and clinical effectiveness of PhEV (compared to VE) established in this work is explained by the significant advantages of the developed technique. Conclusion. The proposed PhEV technique can be recommended for the practice of surgical treatment of patients with RRD in accordance with the established indications.

Aim. To analyze the efficacy and safety of combining nivolumab with AVD chemotherapy (N-AVD) in patients with newly diagnosed classical Hodgkin’s lymphoma in real-world evidence studies.Materials and methods. The retrospective single-center study included 26 patients (14 men, 12 women) with advanced disease stages (IIB with unfavorable prognostic factors according to GHSG (German Hodgkin Study Group) or III–IV according to the Ann Arbor classification). Patients received therapy at the Leningrad Regional Clinical Hospital from March 2023 to February 2025. The N-AVD regimen included nivolumab at a dose of 3 mg / kg (maximum 240 mg), doxorubicin 25 mg / m2, vinblastine 6 mg / m2, and dacarbazine 375 mg / m2 on days 1 and 15 every 28 days. Patients with stage IIB were planned to receive 4 cycles of N-AVD, in case of stages III–IV – 6. Some patients received consolidating proton therapy – 6 (24 %) or 3D conformal radiation therapy – 6 (24 %). The primary endpoint of the study was progression-free survival, and secondary endpoints were the complete remission rate, safety, event-free survival, and overall survival.Results. The complete remission rate was 94 %. With a median follow-up of 11.9 months, 1‑year progression-free survival was 95.7 %, and overall survival – 100 %. The most common adverse events were grade 3–4 neutropenia (46.2 %) and febrile neutropenia (11.5 %). Immune-mediated complications represented by two cases of hypothyroidism and acute pericarditis in one patient.Conclusion. Preliminary results of our study demonstrate the high efficiency of the N-AVD regimen and emphasize the importance of monitoring immune-mediated complications. The advisability of consolidation radiotherapy in patients with complete remission on anti-PD1 monoclonal antibody therapy requires further study. Our study confirms the prospects of using the N-AVD regimen in patients with newly diagnosed classical Hodgkin’s lymphoma, but longer follow-up and a larger sample are needed for conclusions.

Biopsy has limited value and is relatively effective only against cystic tumors for preoperative diagnosis of mediastinal cysts. Noninvasive clinical imaging is relevant here, taking into account the localization of the neoplasm and its relationship to neighboring structures. Non-tumor cysts of the thymus gland (CTG) are divided into monolocular (congenital, primary) and multilocular (acquired, secondary). A clinical case of a 45-year-old woman with a multilocular CTG diagnosed by computed tomography and videothoracoscopically removed is presented. The issues of diagnosis and differential diagnosis of multilocular CTG and their possible connection with COVID 19 are discussed.

The randomized controlled pivotal phase 3 study evaluated efficacy and safety of neoadjuvant complex biologic, Leukocyte Interleukin Injection (LI), administered for 3 consecutive weeks pre-surgery, in treatment naïve resectable locally advanced primary squamous cell carcinoma of oral cavity and soft palate. Randomization 3:1:3 to LI+/-CIZ (cyclophosphamide, indomethacin, and zinc)+SOC, or SOC (standard of care) alone. LI-treated patients received 400IU (as interleukin-2 equivalent; 200IU peritumorally, 200IU perilymphatically) sequentially, daily 5days/week for 3weeks before surgery. All subjects were to receive SOC. Post-surgery, patients with low risk for recurrence were to receive radiotherapy, while those with high risk received concurrent chemoradiotherapy. Median follow-up was 56 months. There were 923 ITT (Intent-to-Treat) subjects (380 ITT low-risk and 467 ITT high-risk). Pre-surgery objective early response (45 objective early responders; 5 complete responses [CRs], 40 partial responses [PRs], confirmed by pathology at surgery. LI (+/- CIZ) had 8.5% objective early responders (45/529 ITT) and 16% objective early responders (34/212 ITT low-risk) vs. no reported SOC objective early responders (0/394 ITT). Objective early responders significantly lowered death rate to 22.2% (ITT LI-treated), 12.5% (ITT low-risk LI + CIZ + SOC), while the ITT low-risk SOC death rate was 48.7%. Thus, objective early response impacted overall survival (OS); proportional hazard ratios were 0.348 (95% CI: 0.152-0.801) for ITT low-risk LI-treated, 0.246 (95% CI: 0.077-0.787) for ITT low-risk LI + CIZ + SOC. ITT low-risk LI + CIZ + SOC demonstrated significant OS advantage vs. ITT low-risk SOC (unstratified log-rank p = 0.048; Cox hazard ratio = 0.68; 95% CI: 0.48-0.95, Wald p = 0.024 [controlling for tumor stage, tumor location, and geographic region]). Absolute OS advantage increased over time for ITT low-risk (LI + CIZ + SOC)-treated vs. ITT low-risk SOC: reaching 14.1% (62.7% vs. 48.6%) at 60months, with 46.5months median OS advantage (101.7months vs. 55.2months), respectively. Quality of life benefit for complete responders sustained for >3years post LI treatment. Percent treatment-emergent adverse events were comparable among all treated groups. No excess safety issues were reported for LI over SOC alone post-surgery. NCT01265849, EUDRA:2010-019952-35.

Objective: to re-evaluate the efficacy and safety of lenvatinib with pembrolizumab in unselected Russian renal cell carcinoma (RCC) patients, included in the phase IV study, in a median follow-up extended to 17.1 months. The primary end point was progression-free survival (PFS), secondary end points were overall survival (OS), objective response rate (ORR) and duration of response (DOR), disease control rate (DCR) and its duration, as well as safety.Materials and methods. The study included medical data of 165 patients with verified advanced RCC who received lenvatinib with pembrolizumab in 36 centers of the Russian Federation from 05.02.2018 to 25.07.2024. The median age was 60 (20–76) years, the male to female ratio was 2.3:1. The majority of patients had Karnofsky performance status ³80 % (74.6 %), clear cell RCC (93.3 %) without sarcomatoid differentiation (93.3 %), metachronous metastases (50.9 %) localized in >1 organ (75.2 %), were nephrectomized (63.0 %) and did not receive antitumor therapy (91.0 %). At the time of lenvatinib with pembrolizumab therapy start 40 patients (24.2 %) were classified into International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) favorable prognostic group, 92 (55.8 %) in the intermediate prognostic group, and 33 (20.0 %) in the poor prognostic group. The median follow-up was 17.1 (1.5–72.9) months.Results. The median PFS achieved 24.0 (18.7–29.3) months, 17-month PFS 60.5 %. The median OS was 48.9 (18.5– 79.2) months, 17-month OS – 76.1 %. Objective response was registered in 46.0 % of patients including 2.4 % complete responders; the DCR was 92.1 %. The median DOR was 16.6 (2.1–72.9) months, duration of disease control –14.3 (2.1–72.9) months. Confirmed dynamics of change in the sum of tumor foci diameters was recorded in 152 patients, while the median change was –25 % (from –100 % to +29 %). Any decrease in the sum of tumor foci diameters occurred in 69.1 % of cases. The incidence of any adverse events (AE) was 78.2 %, severe AE – 24.2 %, and serious AE – 9.7 %. Immune-mediated AEs developed in 17.0 % of cases and AE grades 3–4 in 6.7 % of cases. Mortality from AEs was 1.2 %.Conclusion. Compared with the registration study, in real-world clinical practice in patients with advanced RCC the lenvatinib with pembrolizumab provides a lower ORR with comparable PFS and OS rates and demonstrates a satisfactory safety profile.

LBA105 Background: Use of triplet/quadruplet therapies for 1L MM raises the need for novel combinations at first relapse, which belantamab mafodotin (belamaf) combos may address. In DREAMM-7, BVd led to a significant improvement in progression-free survival (PFS) and a strong trend in improved overall survival (OS) vs daratumumab-Vd in patients (pts) with ≥1 prior therapy. We report results from DREAMM-8 (NCT04484623), which tested a different belamaf combo (BPd) and met its primary endpoint of independent review committee–assessed PFS at a prespecified interim analysis. Methods: DREAMM-8 is a phase 3, open-label, randomized, multicenter trial evaluating the efficacy and safety of BPd vs PVd in RRMM pts who received ≥1 prior line of therapy (LoT), including lenalidomide. Pts were randomly assigned 1:1 to BPd (28-d cycles): belamaf 2.5 mg/kg IV (D1, C1), 1.9 mg/kg (D1, C2+) + pom 4 mg (D1-21, all C) + dex 40 mg (D1, QW, all C), or PVd (21-d cycles): pom 4 mg (D1-14, all C) + bortezomib 1.3 mg/m2 SC (D1, 4, 8, 11 [C1-8]; and D1, 8 [C9+]) + dex 20 mg (day of and 1 day after bortezomib dose). Results: 155 pts were randomly assigned to BPd and 147 to PVd. With a median (range) follow-up of 21.78 mo (0.03-39.23), median PFS (95% CI) was not reached (NR; 20.6-NR) with BPd vs 12.7 mo (9.1-18.5) with PVd (HR, 0.52; 95% CI, 0.37-0.73; P<0.001). 12-month PFS rate (95% CI) was 71% (63-78%) with BPd vs 51% (42-60%) with PVd. ORR (95% CI) was 77% (70.0-83.7%) with BPd vs 72% (64.1-79.2%) with PVd; rate of complete response or better (95% CI) was 40% (32.2-48.2%) with BPd vs 16% (10.7-23.3%) with PVd. Median duration of response (95% CI) was NR (24.9-NR) with BPd vs 17.5 mo (12.1-26.4) with PVd. A positive trend favoring BPd was seen for OS (HR, 0.77; 95% CI, 0.53-1.14); follow up for OS is ongoing. Adverse events (AEs) were reported in >99% and 96% of pts in the BPd and PVd arms, respectively. Of pts treated with BPd, 89% had ocular AEs (CTCAE grade 3/4, 43%) vs 30% (grade 3/4, 2%) in the PVd arm. AEs were generally manageable, and broadly consistent with known safety profile of individual agents. Conclusions: The DREAMM-8 study demonstrated a statistically significant and clinically meaningful PFS benefit with BPd vs PVd in RRMM with >1 prior LoT. BPd also led to deeper and more durable responses, showed a favorable OS trend, and had a manageable safety profile. Clinical trial information: NCT04484623 . [Table: see text]

The article presents the results of the three-year use of netakimab (NTK) in patients with ankylosing spondylitis (AS) as part of the phase III BCD-085-5/ASTERA study.Objective: to evaluate the long-term efficacy and safety of NTK over a three-year period in patients with active AS.Material and methods. BCD-085-5/ASTERA – double-blind, multicenter, randomized phase III clinical trial that enrolled patients with active AS (BASDAI ≥4) and a back pain intensity ≥4 on a numeric rating scale with inefficacy or intolerance of non-steroidal anti-inflammatory drugs or biologic drugs. A total of 228 patients were randomized in a 1:1 ratio and assigned to either the NTK group or the placebo/NTK group. Starting at week 16, patients who did not achieve ASAS20 (20% improvement according to ASAS criteria) received NTK 120 mg once every 2 weeks in an open-label regimen. Patients who achieved ASAS20 response at week 52 in the NTK group and week 68 in the placebo/NTK group continued to receive NTK (120 mg every 2 weeks) until week 156 in the NTK group and until week 172 in the placebo/NTK group.Results and discussion. Over the course of three years of NTK use, most patients experienced a sustained decline in AS activity (according to ASDAS-CRP, BASDAI) with sustained response (ASAS20/40, ASAS5/6) to therapy. Most adverse events reported were mild to moderate. 36.7% of patients had adverse events, which were mainly laboratory abnormalities, blood and lymphatic system abnormalities and infectious complications.Conclusion. The clinical effect of NTK was maintained in most patients with AS over a three-year period, with no significant loss of response. NTK was well tolerated and the safety profile remained favorable.