Molecularly Adapted Antitumor Therapy for Newly Diagnosed Diffuse Large B-Cell Lymphoma: Two-Year Follow-Up Results
Year: 2026
Type: article
Study design: Clinical Trial
Abstract: 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.
Source: Journal of Clinical Medicine
DOI: 10.3390/jcm15082983
Authors: Marat Mingalimov, Elena Baryakh, Andrey Misyurin, Laura Kesaeva, Hasmik Mkrtchyan, Elena Misyurina, Mariia Orlova, Tatiana Tolstykh, Ekaterina Zotina, Liliia Shimanovskaia, Tatiana Chudnova, Diana Ivanova, Olga Kochneva, Кseniya Tsurkina, Dmitry Lebedev, Georgii Tyshkevich, Natalia Bekreneva, Viktoriia Basova, Mikhail Donskoy, Sergej Rodnikov, Ivan Abramov, Natalia Bodunova, Saida M. Gadzhieva, Tatiana Semina, Sergey Andreev, Inna Samsonova, Мariana Lysenko
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,137
OpenAlex ID: W7154237405