Large B-cell lymphoma (LBCL): EHA Clinical Practice Guidelines for diagnosis, treatment, and follow-up.
- Study type
- Clinical guideline
- Study name
- EHA LBCL 2025
- Design
- Clinical guideline of the European Hematology Association (EHA); levels of evidence (I to V) and grades of recommendation (A to E) according to a grading system adapted from the Infectious Diseases Society of America (IDSA)
- Source
- Hemasphere · 2025
In plain words
This European guideline explains how large B-cell lymphoma should be diagnosed, staged and treated. For most patients, the first treatment is the R-CHOP regimen, and in more advanced disease with several risk factors the Pola-R-CHP regimen (in which the targeted drug polatuzumab takes the place of vincristine) is suggested. If the disease comes back early (within a year), CAR-T cell therapy is recommended; if it comes back later, chemotherapy followed by a transplant of the patient's own stem cells. For people who cannot cope with these intensive treatments, there are gentler options. Your doctor will decide based on your own situation.
Key guideline recommendations
- I, B
First-line treatment, stage 1 or 2 without risk factors and age under 80 years: four cycles of R-CHOP21 are suggested; in bulky disease, six cycles of R-CHOP21 (level I, A) should be considered.
- I, A
First-line treatment with one risk factor (stage 3 or 4, or stage 1 or 2 with poor performance status or elevated LDH) and age under 80 years: six cycles of R-CHOP21 are suggested.
- I, B
First-line treatment in stage 3 or 4 with two or more risk factors and age under 80 years: six cycles of Pola-R-CHP (polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin and prednisone) are suggested; R-CHOP21 should be considered as an alternative (level I, A).
- III, B
A biopsy is strongly recommended before starting second-line treatment.
- I, A
Patients with refractory disease or relapse less than 12 months after the end of first-line treatment: CAR-T cell therapy, i.e. axicabtagene ciloleucel or lisocabtagene maraleucel, is suggested. CAR-T therapy may not be suitable for patients with performance status 2 or higher, high tumour burden and/or rapidly rising LDH.
- I, B
Patients relapsing more than 1 year after the end of first-line treatment who are fit for intensive treatment: salvage immunochemotherapy (R-DHAX [P or C], R-ICE, R-GDP, R-ESHAP) and, if chemosensitive (complete metabolic response or very good partial response), high-dose chemotherapy (BEAM, BEAC, BeEAM or FEAM) followed by autologous stem cell transplantation (ASCT).
- III, B
Patients ineligible for CAR-T therapy (relapse less than 12 months) or ineligible for high-dose chemotherapy and ASCT (relapse more than 12 months): R-GemOx (rituximab, gemcitabine and oxaliplatin) or pola-BR (polatuzumab, bendamustine and rituximab) is suggested.
- I, A (glofitamab) · III, C (epcoritamab)
In patients ineligible for ASCT, glofitamab plus GemOx (level I, A) or epcoritamab plus GemOx (level III, C) should be considered.
Study population
Adults with large B-cell lymphoma (LBCL), including diffuse large B-cell lymphoma, high-grade B-cell lymphoma with MYC and BCL2 rearrangements, primary mediastinal large B-cell lymphoma and elderly patients.
Endpoints
This document is not a trial; it provides recommendations for diagnosis, staging, first-line treatment, treatment of relapsed or refractory disease and follow-up.
Safety and side effects
The guideline emphasises follow-up and management of late treatment effects such as cardiotoxicity, osteoporosis, immune dysfunction, neurocognitive impairment, endocrine dysfunction, fatigue, neuropathy and psychological distress.
Clinical significance and place in guidelines
The 2025 EHA guideline stratifies first-line treatment by stage and number of risk factors (R-CHOP for lower risk and Pola-R-CHP for stage 3 or 4 with two or more risk factors) and, in second line, recommends CAR-T for early relapse (less than 12 months) and salvage immunochemotherapy followed by high-dose chemotherapy and ASCT for late relapse.
Limitations
Some recommendations (such as CNS prophylaxis and regimens for double-hit and triple-hit lymphomas) are based on level III or IV evidence, and the authors note that the evidence is insufficient. The recommendations were developed for European health systems.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.