Personalized genotype-directed antitumor therapy for newly diagnosed diffuse large B-cell lymphoma: efficacy and toxicity of the R-CHOP-X protocol in a single-center, non-randomized, prospective clinical trial (first results)

Background. Diffuse large B-cell lymphoma (DLBCL) is a potentially curable biologically heterogeneous lymphatic tumor. Standard R-CHOP therapy shows disappointing results, both immediate and longterm. To improve efficacy without additional toxicity, it is worth considering the possibility of using biologically oriented therapy.Aim. To evaluate the clinical efficacy and toxicity of the genotypedirected R-CHOP-X in patients with newly diagnosed DLBCL in real clinical practice.Materials and methods. A single-center prospective interventional clinical study included 30 patients with newly diagnosed DLBCL between September 2023 and September 2024. The median age was 60 (38–78) years. According to the international prognostic index, 23 (77 %) patients were classified as having a high risk of progression. Genotype incidence in the study cohort: MCD – 7 %, N1 – 20 %, BN2 – 7 %, EZB– 16 %, ST2 – 7 %, NOS – 43 %.Results. 30 patients received personalized genotype-directed therapy. Of these, 21 (70 %) patients completed treatment: the overall response rate was 100 % (complete metabolic response – 100 %). 9 (30 %) patients continue therapy: the overall response rate is 100 %. At 12 months, overall survival and progression-free survival were 100 % (95 % confidence interval 100 %). Hematological toxicity was assessed depending on the number of cycles (n = 144): grade III–I neutropenia was detected in 7 % of cycles, grade III–I anemia and grade III–I thrombocytopenia in 1.4 and 3.5 % of cycles, respectively. Non-hematological toxicity was generally grade ≤I–II.Conclusion. The results of this clinical trial are promising and provide preliminary evidence for the benefit of personalized genotype-directed antitumor therapy in newly diagnosed DLBCL. This therapeutic strategy demonstrates high clinical efficacy, particularly in the main target group – DLBCL with a high risk of progression with low toxicity. Further randomized studies are needed to confirm the effectiveness and implement the new approach in routine clinical practice.