Vol 28, No 2 (2026)

On May 15, 2026, Moscow hosted the 37th Lymphorum Interactive Expert Forum, which focused on contemporary approaches to the diagnosis and treatment of lymphoproliferative diseases. The interactive format of this event included the analysis of challenging clinical cases in collaboration with clinicians, pathomorphologists, and clinical experts. This review presents an analysis of 10 clinical cases presented during the forum sessions, along with insights from pertinent studies that underpin current pharmacological strategies for patients with lymphoproliferative diseases. Such scientific events underscore the importance of collaborative efforts among specialists from diverse fields to enhance treatment outcomes and improve the quality of life for patients with oncohematological diseases.

Background. This article presents a thorough medical and legal examination of the principle of "discretion" in the surgical management of malignancies. The significance of this study arises from the mandatory implementation of clinical guidelines effective January 1, 2022, in accordance with Article 37 of Federal Law No. 323-ФЗ. This legislation has notably restricted the scope for individualized medical decision-making. At the same time, the complete algorithmization of surgical oncology remains fundamentally impossible due to the unique features of each clinical case. The authors interpret medical discretion as a specific form of administrative discretion – a legally conferred right enabling physicians to make informed and independent decisions based on clinical circumstances, evidence-based data, and the overarching principle of safeguarding the patient's health.

Aim. To provide a comprehensive medical and legal analysis of the "discretion" principle within the surgical phase of cancer treatment, including examining its legal boundaries, its relationship with clinical guidelines, and the notion of informed voluntary consent, as well as an assessment of relevant law enforcement practices.

Materials and methods. The study used system analysis, formal legal analysis, comparative law, and content analysis of judicial rulings. A total of 87 judicial decisions about civil cases from 2018 to 2025, relevant regulatory frameworks, and clinical guidelines issued by the Ministry of Health of Russia, the Association of Oncologists of Russia, the Russian Society of Clinical Oncology (RUSSCO), as well as NCCN and ESMO guidelines, along with the 8th edition of the TNM classification of malignant tumors, were reviewed.

Results. The findings indicate that discrepancies in clinical and pathomorphological staging, which may reach up to 23.9% in colorectal cancer, render intraoperative approach adjustments a necessary practice. Analysis of specific court cases revealed that the legitimacy of extending the surgical intervention is evaluated not by the outcome but by the appropriateness of the surgeon's actions at the time they were performed, based on the intrinsic connection between surgical practices and pathological morphology, thereby facilitating a clear distinction in responsibility between surgery and pathology teams. Particular importance is attached to informed voluntary consent; it is the substance and completeness of this consent – rather than the mere availability of the document itself – that serves as the decisive mechanism for risk allocation.

Conclusion. The authors establish criteria for the legality of extending the surgical intervention and advocate for enhancements to clinical guidelines, the format of informed voluntary consent, surgical protocols, the introduction of a standard for the "reasonable surgeon," and the legislative endorsement of the concept of "reasonable medical risk."

On January 16, 2026, a meeting of the Expert Council entitled "Hepatocellular Carcinoma: Modeling the Present Future" convened in Moscow, featuring contributions from specialists across leading medical centers in the Russian Federation. The primary focus of this meeting was to evaluate the potential application of CAR-T cell therapy in patients with unresectable hepatocellular carcinoma at second-line or later treatment. The discussions encompassed the profile of an appropriate candidate for therapy, including tumor burden, Eastern Cooperative Oncology Group (ECOG) performance status, Child-Pugh and ALBI scores, and any concomitant diseases. Furthermore, the Council assessed the anticipated impact of introducing innovative cellular technologies on the overall survival of this patient cohort. Special emphasis was placed on the novel CAR-T product AZD7003, characterized by anti-GPC3 targeting and anti-TGF-β enhancement.

Background. Breast cancer (BC) is a heterogeneous disease that presents significant challenges in treatment planning. A short-term preoperative test for hormone sensitivity (THS) is one approach to personalizing adjuvant systemic therapy for patients with BC. Despite its availability for over 25 years, several unresolved issues continue to limit the widespread adoption of test hormone therapy in clinical practice.

Aim. To evaluate changes in morphological and immunohistochemical parameters during preoperative THS in patients with luminal HER2-negative BC and to identify factors influencing these changes.

Materials and methods. The study cohort comprised 254 patients with luminal HER2-negative BC treated at the Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology between 2018 and 2024. During the preoperative stage, core biopsies of breast tumors were obtained, followed by administration of short-term THS. Premenopausal patients received tamoxifen with or without ovarian suppression using goserelin, while postmenopausal patients received aromatase inhibitors. Post-surgical assessment included evaluation of changes in tumor proliferative activity, as measured by degree of malignancy (G) and Ki67 levels, as well as changes in estrogen receptor (ER) and progesterone receptor (PR) expression in surgical specimens.

Results. Following short-term THS, a statistically significant decrease was observed in the expression of ER (p<0.001), PR (p<0.001), Ki67 (p<0.001), and degree of malignancy (p=0.031). Multivariate regression analysis identified baseline Ki67 (p<0.001), drug type (p=0.012), and ER expression (p=0.012) as significant predictors of Ki67 reduction.

Conclusion. Alterations in hormone receptor expression, Ki67, and degree of malignancy during preoperative THS facilitate prediction of clinical response and assessment of endocrine therapy effectiveness in vivo within a short timeframe. This approach may allow some patients to avoid unnecessary and highly toxic chemotherapy.

Background. Despite improved outcomes with immune checkpoint inhibitors in first- or second-line advanced non-small-cell lung cancer (NSCLC) settings, a significant patient population has emerged that either does not respond to or progresses during anti-PD-(L)1-containing therapy. Following progression on platinum-based chemotherapy and PD-(L)1 inhibitor therapies, treatment options for patients with NSCLC are limited.

Aim. To evaluate the clinical efficacy and safety of ceralasertib combined with durvalumab for the treatment of advanced or metastatic NSCLC without actionable genomic alterations.

Materials and methods. This multicenter, single-arm, phase II study (NCT05941897; randomized clinical trial No. 88, dated February 21, 2023) conducted in Russia enrolled patients with EGFR and ALK wild-type NSCLC who had progressed on first- or second-line platinum-doublet chemotherapy and anti-PD-(L)1 immunotherapy. Eligible patients received oral ceralasertib 240 mg twice daily for 7 consecutive days followed by durvalumab 1500 mg as an intravenous infusion in continuous 28-day treatment cycles until disease progression, unacceptable toxicity, or death. The primary endpoint was investigator-assessed objective response rate (ORR). Secondary endpoints included disease control rate at 18 weeks (DCR), progression-free survival (PFS), duration of response, overall survival (OS), and safety.

Results. Between June 2023 and July 2025, 55 patients were screened, of whom 39 received ceralasertib plus durvalumab. The median follow-up time was approximately 9 months. The confirmed ORR was 10.3% (4/39; 95% confidence interval [CI] 2.9–24.2), and DCR was 53.8% (21/39; 95% CI 37.2–69.9). Median PFS was 6.41 months (95% CI 3.71–8.28) and median OS was 18.04 months (95% CI 8.84–23.23). Adverse events (AEs) were reported in 31 patients (79.5%), with 11 (28.2%) experiencing grade ≥3 events. The most common AEs were nausea (53.8%), vomiting (23.1%), respiratory tract infection (20.5%), anemia (15.4%), asthenia (15.4%), fatigue (15.4%), and diarrhea (12.8%). No treatment-related serious adverse events or deaths occurred.

Conclusion. The combination of ceralasertib and durvalumab demonstrated a manageable safety profile with clinical activity (as evidenced by PFS and OS) in second- or third-line treatment of patients with advanced or metastatic NSCLC without actionable genomic alterations. These findings support further investigation of this combination in selected patient populations.

Background. The long-acting granulocyte colony-stimulating factor (G-CSF) pegfilgrastim has proven to be an effective option for primary febrile neutropenia (FN) prophylaxis. Its efficacy has been demonstrated across a wide range of malignancies, chemotherapy regimens, and varying baseline risks of FN. Prophylactic use of G-CSF reduces not only the risk of developing FN but also the risk of early death, including infection-related mortality. Currently, available literature lacks information on the real-world clinical practice of using pegfilgrastim in patients with lymphomas receiving intensive chemotherapy for remission induction prior to high-dose therapy with autologous hematopoietic stem cell transplantation, including data on the pharmacoeconomic aspects of these prophylactic measures.

Aim. Based on real-world clinical practice data, to evaluate the clinical and economic consequences of G-CSF use in lymphoma patients undergoing high-dose polychemotherapy (PCT) prior to autologous hematopoietic stem cell transplantation.

Materials and methods. The study included 104 patients with lymphoma who received short-acting G-CSF filgrastim (n=30) or long-acting empegfilgrastim (n=74) at the Department of Hematology and Bone Marrow Transplantation Pirogov National Medical and Surgical Center. Based on real-world clinical practice data, the effectiveness of FN prophylaxis was assessed, including the incidence of FN, length of hospital stay, and impact on intervals between PCT cycles. Budget impact analysis was performed for a population of 100 patients, considering only costs for drug therapy with comparator agents and costs for treating FN episodes.

Results. Compared with filgrastim, empegfilgrastim use reduced the proportion of PCT cycles leading to FN from 16 to 1% (p<0.001) and the proportion of patients experiencing an FN episode from 23 to 3% (p<0.001). Budget impact analysis for a population of 100 patients showed that direct medical costs with filgrastim therapy were 0.6 million RUB (5%) higher, totaling 13.6 million RUB, compared to 13.0 million RUB with empegfilgrastim therapy. In the cost structure, when using empegfilgrastim, the main expenses were for FN prophylaxis, accounting for 95% (12.5 million RUB), whereas with filgrastim therapy, the main costs (67%, 9.17 million RUB) were for treating FN episodes that occurred, with prophylaxis costs accounting for only 32%. Although the cost of a single empegfilgrastim administration is higher than that of filgrastim (41.5 thousand RUB versus 14.9 thousand RUB for 5.5 days of therapy), subsequent costs for treating FN episodes offset the expected savings.

Conclusion. Primary neutropenia prophylaxis with empegfilgrastim allows for a statistically significant reduction in adverse events without increasing healthcare system costs and therefore can be recommended for widespread use.

Aim. To evaluate the safety of four regimens of Bacillus Calmette-Guérin (BCG) therapy following transurethral bladder resection in patients diagnosed with intermediate- and high-risk non-muscle-invasive bladder cancer.

Materials and methods. This study is a prospective, interventional, four-arm, open-label, randomized phase II clinical trial with a non-inferiority design. The main inclusion criteria were histologically confirmed non-muscle-invasive bladder cancer of intermediate or high risk in patients aged 18 years or older who have undergone transurethral resection of the bladder. Participants were randomized into four treatment groups in a 1:1:1:1 ratio for intravesical therapy utilizing the BCG vaccine: test groups 1 (50 mg, 1 year), 2 (50 mg, 3 years), 3 (100 mg, 1 year), and a control group 4 (100 mg, 3 years). The primary endpoint of the randomized controlled trial was the one-year local recurrence rate, while secondary endpoints reported in this publication included safety and toxicity.

Results. The second interim analysis, with a median follow-up of 16.7 months (range: 2.5–33.6 months), included data from 401 patients with a median age of 66.4 years (range: 31–95 years). Within the EORTC intermediate-risk group, 93 patients (23.2%) were included, while the high-risk group comprised 308 patients (76.8%). All patients received BCG therapy according to their assigned randomization group: group 1 – 100 patients (24.9%); group – 92 patients (23.0%); group 3 – 109 patients (27.2%); group 4 – 100 patients (24.9%). The treatment groups were balanced with respect to the main characteristics. A total of 133 patients (33.2%) and 184 patients (45.9%) required an adjustment in the interval between induction and maintenance instillations, respectively. The induction completion rate was 96.8%, while the maintenance administration rate was 86.0%. Adverse events (AEs) were reported in 363 patients (90.5%), with 40 events (10.0%) reaching grades 3–4, requiring hospitalization in 14 patients (3.5%). The most prevalent local AEs included dysuria (339 patients; 84.5%), hematuria (45 patients; 11.2%), and nonspecific urinary infection (42 patients; 10.5%). Systemic AEs included hyperthermia, affecting 85 patients (21.2%). Tuberculosis was diagnosed in 3 patients (0.7%). The analysis indicated no significant differences in the safety profile or toxicities among the study regimens when compared with the standard regimen.

Conclusion. The findings from the second interim safety analysis do not support the hypothesis that the tolerability of the BCG regimen can be enhanced by reducing its intensity.

Aim. To investigate the predictive value of baseline erythroblasts in selecting patients with metastatic hormone-sensitive prostate cancer (mHSPC) for triplet therapy.

Materials and methods. We provided a multicenter retrospective study that included patients treated between 2022 and 2024 for high-volume mHSPC according to CHAARTED criteria who received either doublet [androgen deprivation therapy (ADT) + an androgen receptor pathway inhibitor (ARPI)] or triplet (docetaxel + ADT + ARPI) therapy. The primary endpoint was 2-year progression-free survival (PFS), defined as time from treatment initiation to clinical or radiological progression, initiation of new systemic therapy, or death from any cause. Cardinality matching at a 2:1 ratio was performed to balance potential confounding variables.

Results. A total of 234 patients were included (141 triplet, 93 doublet). After matching, 122 patients remained in the triplet group and 61 in the doublet group. With a median follow-up of 23.5 months for the triplet group and 33.9 months for the doublet group, 2-year PFS rates were 71.9 and 57.8%, respectively (HR 0.62, 95% CI 0.40–0.95; p=0.027). Subgroup analysis demonstrated significantly greater survival benefit from triplet therapy in patients with detectable baseline erythroblasts (PFS: HR 0.29, 95% CI 0.11–0.76; OS: HR 0.24, 95% CI 0.07–0.77) compared to those without erythroblasts (PFS: HR 0.66, 95% CI 0.37–1.19; OS: HR 0.52, 95% CI 0.26–1.06).

Conclusion. The baseline presence of circulating erythroblasts serves as a strong predictive marker for benefit from docetaxel intensification in patients with high-volume mHSPC. This readily available biomarker may guide patient selection for triplet therapy, pending prospective validation.