Background/Objectives: Diffuse large B-cell lymphoma (DLBCL) is molecularly heterogeneous, and approximately 30-50% of patients fail to achieve cure with standard R-CHOP. Genotype-directed first-line therapy may improve outcomes by targeting subtype-specific oncogenic pathways. This study evaluated the feasibility, efficacy, and safety of a molecularly adapted R-CHOP-X strategy with two-year follow-up. Methods: In this single-center, prospective, non-randomized study conducted between September 2023 and the data cut-off (16 September 2025), 43 adults with newly diagnosed DLBCL (excluding high-grade B-cell lymphoma, primary immune-privileged, and primary mediastinal large B-cell lymphomas) underwent tumor genotyping using the LymphGen classification after targeted sequencing: a 19-gene Sanger panel (Cohort 1, n = 35) or an expanded 60-gene panel (Cohort 2, n = 8; proof-of-concept). All patients received one initial cycle of R-CHOP as bridge therapy pending molecular profiling results, followed by five cycles of R-CHOP-X, with the additional agent (vorinostat, acalabrutinib, decitabine, or lenalidomide) selected according to molecular subtype. Response was assessed by PET/CT per Lugano criteria; adverse events were graded per NCI CTCAE v5.0. Results: The overall study population was predominantly high-risk: 72% had an IPI of 3–5, 58% had stage III–IV disease, and 67% exhibited a non-GCB immunophenotype. Expansion from the 19-gene to the 60-gene panel reduced unclassifiable (NOS) cases from 34% to 12%. The overall response rate was 100% (43/43); complete response among patients completing therapy was 100% (35/35). At two years, overall survival was 92% (95% CI 83–100%) and progression-free survival was 94% (95% CI 86–100%). Two early relapses occurred (NOS and N1 subtypes), both resulting in death. Grade 3–4 neutropenia, thrombocytopenia, and anemia occurred in 26%, 12%, and 7% of patients, respectively; no dose reductions or treatment discontinuations were recorded. Conclusions: Molecularly adapted R-CHOP-X is feasible and associated with high response rates and favorable two-year survival in newly diagnosed DLBCL, comparing favorably with historical R-CHOP outcomes in high-risk populations. Expanded genomic panels substantially improve molecular classifiability. These findings warrant validation in larger, multicenter, randomized clinical trials.

Diffuse large B-cell lymphoma (DLBCL) is molecularly heterogeneous; genotype-directed first-line therapy may improve outcomes. We conducted a single-center, prospective, non-randomized interventional study evaluating a molecularly adapted R-CHOP-X strategy with two-year follow-up. Between February 2023 and the data cut-off (September 16, 2025), 43 adults with newly diagnosed DLBCL (excluding high-grade B-cell lymphoma, primary immune-privileged, and primary mediastinal large B-cell lymphomas) underwent tumor genotyping using LymphGen after targeted sequencing: an initial cohort had Sanger sequencing of a 19-gene panel (n = 35) and a second cohort an expanded 60-gene panel (n = 8). All patients received one cycle of R-CHOP followed by five cycles of R-CHOP-X, with the additional agent (vorinostat, acalabrutinib, decitabine, or lenalidomide) selected according to molecular subtype. Response assessment followed Lugano criteria; adverse events were recorded per NCI CTCAE v5.0. The overall response rate was 100% (n = 43); complete response among patients completing therapy (n = 35) was 100%. At two years, overall survival was 92% (95% CI 83%–100%) and progression-free survival was 94% (95% CI 86%–100%); two early relapses occurred. These findings indicate that molecularly adapted R-CHOP-X is feasible and associated with high response rates and favorable two-year survival and warrant validation in larger randomized clinical trials.

Classical Hodgkin’s lymphoma (cHL) is a lymphoproliferative disease characterized by the presence of Hodgkin anderezovsky–Reed–Sternberg cells and a tumor microenvironment. Currently, much attention is paid to the microenvironment in cLH. A detailed understanding of the interaction between the tumor and its microenvironment opens up prospects for the cHL diagnosis and treatment. Innovative immunotherapeutic agents such as nivolumab make it possible to control and activate the immune response. Despite the high efficiency of standard protocols in young patients, therapy intensification is associated with organ toxicity and the development of secondary malignant neoplasms. At the same time, in elderly patients, the results of generally accepted antitumor treatment protocols should be considered suboptimal. In the last decade, the treatment of refractory cHL has improved significantly due to the use of immune checkpoint inhibitors.Taking into account the above, the priority issue in modern clinical hematology is to improve cHL treatment strategies not only in elderly but also in young patients by maintaining a balance between high efficacy and low toxicity. Moreover, the inclusion of nivolumab in first-line therapy is not only pathogenetically justified and effective, but also safe. The article presents data from clinical observations of the successful nivolumab use in combination with chemotherapy in patients with newly diagnosed cHL.

Background. The use of molecular genetic profiling in clinical practice and the registration of immunotargeted agents have undoubtedly led to the development of a personalized approach in oncohematology, with diffuse large B-cell lymphoma (DLBCL) being no exception. Elderly patients represent a complex group of patients with DLBCL, which leads to difficulties in treatment due to their comorbidity.Aim. To evaluate the efficacy, tolerability and safety of an individualized approach based on the mutational landscape in elderly patients with newly diagnosed DLBCL.Materials and methods. The clinical study included 10 elderly patients with newly diagnosed DLBCL. The median age was 68 (65–78) years. Eight patients were classified as being at high risk of early progression according to the international prognostic index. The frequency of genotypes in the considered cohort of elderly patients: MCD – 1 (10 %), N1 – 3 (30 %), BN2 – 1 (10 %), EZB – 2 (20 %), NOS – 3 (30 %).Results. Overall and complete metabolic response rates were 100 %. Clinically significant hematological toxicity depending on the number of cycles (n = 60): grade III–IV neutropenia in 5 cycles, grade III–IV thrombocytopenia in 2, grade III–IV anemia in 3. Non-hematological toxicity did not exceed grades I–II.Conclusion. High efficacy and low toxicity profile of a personalized approach in elderly patients with newly diagnosed DLBCL were demonstrated. The obtained preliminary results indicate the possibility of continuing the developed clinical study of elderly patients with DLBCL.

Background: Diffuse large B-cell lymphoma (DLBCL) with TP53 abnormalities, corresponding to the LymphGen A53 molecular subtype, represents a biologically high-risk group associated with primary resistance to standard R-CHOP therapy. Epigenetic sensitization using hypomethylating agents may enhance chemosensitivity in this setting. We prospectively evaluated the clinical activity and safety of a molecularly adapted DAC-R-CHOP regimen in newly diagnosed A53-DLBCL. Methods: In this single-center prospective pilot cohort study, 70 consecutive patients with newly diagnosed DLBCL underwent targeted next-generation sequencing using a 60-gene panel with integrated copy number variation analysis. Six patients (8.5%) were classified as the A53 subtype. All patients received one cycle of standard R-CHOP. From cycle 2 onward, A53 patients received decitabine (10 mg/m² IV, days 1–5) prior to R-CHOP (DAC-R-CHOP), for a total of six cycles. The primary endpoint was complete metabolic response (CMR) according to Lugano 2014 criteria. Exact 95% confidence intervals (CI) were calculated. Results: The median age of the A53 cohort was 65 years. CMR was achieved in all six patients (100%; 95% CI, 54%–100%). At a median follow-up of 6 months, all patients remained alive in confirmed CMR. Grade III–IV hematologic toxicity occurred in all cases. Febrile neutropenia developed in 100% of patients, requiring mandatory G-CSF support and anti-infective therapy; no treatment-related mortality or permanent dose reductions were observed. Two patients (33%) experienced gastrointestinal bleeding related to local tumor lysis, which was managed conservatively without protocol discontinuation. Conclusions: In this prospective molecularly stratified pilot cohort, integration of decitabine into front-line immunochemotherapy showed promising clinical activity in A53-DLBCL, albeit at the cost of substantial hematologic toxicity requiring intensive supportive care. Given the small sample size, short follow-up, and absence of a comparator arm, these findings should be considered hypothesis-generating and warrant validation in larger multicenter phase II studies with integrated translational biomarker analyses.

Background. Despite tremendous progress in understanding tumor biology, the R-CHOP protocol remains the standard of care for diffuse large B-cell lymphoma (DLBCL). To date, six genetic variants of DLBCL have been identified, the most unfavorable of which when using standard therapy are N1, MCD and BN2, which dictates the need to optimize the treatment of these DLBCL subtypes.Aim. To evaluate the efficacy and toxicity of Acala-R-CHOP regimen in induction therapy in patients with newly diagnosed DLBCL.Materials and methods. The study included 15 patients who received Acala-R-CHOP program as part of the first-line therapy. This antitumor regimen was used for verified genotypes N1, MCD and BN2. The median age was 64 (38–78) years. The incidence of genetic variants in the considered cohort of patients: MCD – 13 % (n = 2), N1 – 74 % (n = 11), BN2 – 13 % (n = 2).Results. Fifteen patients completed the therapy. The overall and complete metabolic response rates were 100 %. Toxicity was moderate, quite manageable and manifested mainly as myelosuppression.Conclusion. The efficacy of Acala-R-CHOP therapy in patients with MCD, N1, and BN2 DLBCL genotypes is high with a low toxicity profile. However, longer follow-up periods are needed to assess the long-term results in this unfavorable group of patients.