Diffuse large B-cell lymphoma

Diagnosis requires tissue showing large malignant B cells with the appropriate immunophenotype. DLBCL, not otherwise specified, is distinguished from entities such as primary mediastinal B-cell lymphoma and from lymphoma arising in the central nervous system. An organ location can change the necessary treatment strategy.

Cell-of-origin categories include germinal-center B-cell and activated B-cell patterns. An immunohistochemical surrogate is not identical to gene-expression testing. Molecular subgroups can inform prognosis and research, but a label alone does not authorize every targeted therapy.

MYC and BCL2 protein expression is measured by immunohistochemistry. Rearrangements are genetic changes, often evaluated with FISH. A double-expressor result does not establish a double-hit lymphoma, and treatment should not be intensified solely because these phrases sound similar.

Current classifications distinguish disease with MYC and BCL2 rearrangements from other genetic combinations; older reports may group MYC/BCL6 disease differently. Ask whether the final diagnosis, rather than just an isolated FISH result, has been reviewed under the current classification.

Baseline PET/CT, LDH, blood counts, organ function and performance status help determine disease extent and risk. The International Prognostic Index is a risk tool, not a personal survival prediction. Stage IV can still be treated with curative intent.

Heart function, frailty, infection history and neuropathy affect the regimen and support required. In older adults, geriatric assessment can distinguish a fit patient from someone needing reduced intensity or an anthracycline alternative. Age alone is an incomplete assessment.

R-CHOP combines rituximab with cyclophosphamide, doxorubicin, vincristine and prednisone. Pola-R-CHP replaces vincristine with the CD79b-directed antibody-drug conjugate polatuzumab vedotin. The US first-line polatuzumab indication specifies adult DLBCL NOS or high-grade B-cell lymphoma with IPI at least 2.

Five-year POLARIX follow-up continued to show a progression-free survival benefit, without a statistically significant overall-survival difference in the overall analysis. This should not be advertised as proof that every patient lives longer. The report has a published correction, which matters when interpreting genetic subgroup plots.

Limited-stage disease may use a shorter or PET-adapted course and selected radiotherapy. Particular high-grade genetic entities may warrant a different regimen or trial. The decision should specify the entity, risk and evidence rather than assuming that increasing chemotherapy intensity benefits all DLBCL.

Neurological symptoms require investigation for actual CNS involvement, which needs a different treatment plan. CNS-IPI, particular extranodal sites and biology help identify patients who may need further assessment even without symptoms.

Preventive high-dose methotrexate is not a universal requirement. Its benefit remains debated, including in recent large analyses, while kidney toxicity and delays to curative systemic treatment are real considerations. Ask about the expected individual benefit, timing and alternatives; treating established CNS disease is not the same as prophylaxis.

End-of-treatment PET is interpreted using standardized response criteria. A remaining mass without active uptake can represent a complete metabolic response. A positive focus may need tissue confirmation before a major change in treatment because inflammation or infection can mimic lymphoma.

Recent TRANSFORM analyses show that circulating tumor DNA clearance adds prognostic information beyond imaging. This is promising complementary evidence, not a universal instruction to stop, intensify or replace therapy based on one blood test. Assay, time point and clinical context matter.

For eligible large B-cell lymphoma that is refractory to first-line therapy or relapses within 12 months, axi-cel and liso-cel have second-line indications in defined settings. ZUMA-7 demonstrated an overall-survival benefit for axi-cel over the strategy of salvage chemotherapy followed by transplantation when responsive.

Referral should occur while disease can still be controlled. Collection of T cells, manufacturing, bridging therapy and travel/support needs require coordination. Prior drugs can affect cell collection; starting another salvage course without discussing the cellular-therapy plan may complicate sequencing.

CAR-T is not interchangeable across products. CRS, neurological toxicity, cytopenias, infection and long-term monitoring must be considered. Inability to tolerate autologous transplantation does not automatically exclude all CAR-T options; eligibility needs a separate assessment.

When relapse occurs later and disease remains sensitive to salvage chemotherapy, high-dose therapy with autologous stem-cell rescue remains a potentially curative route for suitable patients. PET response, organ reserve and stem-cell collection feasibility guide that decision.

Relapse should usually be re-biopsied when feasible, particularly after a long remission or if one site behaves differently. A trial, CAR-T or another systemic option may be more appropriate when disease is resistant, transplant is unsuitable or previous treatment changes the balance.

CD20×CD3 bispecific antibodies bring T cells close to malignant B cells. US epcoritamab and glofitamab monotherapy indications specify eligible relapsed/refractory large B-cell diseases after at least two prior systemic lines. They may be useful after CAR-T or when that route is unsuitable, but sequencing depends on prior targets and disease pace.

STARGLO and its three-year follow-up support glofitamab-GemOx for transplant-ineligible relapsed/refractory DLBCL compared with R-GemOx. The EU authorizes this combination for the specified population; the US Columvi label remains different. Do not infer US combination approval from the European indication.

Other possibilities include antibody-drug conjugates and selected antibody combinations. In the US, brentuximab vedotin with lenalidomide and rituximab is approved after at least two lines for specified LBCL when autologous transplantation or CAR-T is unsuitable. Selection is individualized, not a ranking based on response rates from unrelated trials.

Anti-CD20 treatment can reactivate hepatitis B. Screening, antiviral prevention when indicated, vaccination planning and infection monitoring belong in the treatment plan. Tumor lysis prevention may be needed before rapidly effective treatment, especially with bulky disease or impaired kidney function.

Bispecific antibodies require product-specific step-up dosing and monitoring. In addition to CRS and infection, the Columvi safety update highlights hemophagocytic lymphohistiocytosis, a potentially life-threatening inflammatory complication. Persistent fever with clinical deterioration requires urgent assessment, not self-treatment as an ordinary infusion reaction.

Bring full pathology including MYC/BCL2/BCL6 testing where performed, PET/CT images, every regimen and response date, prior toxicities and the most recent blood and organ-function results. Include dates of progression relative to the end of first-line treatment.

Ask which decision is urgent: confirming the subtype, starting curative treatment, collecting cells or controlling disease while a definitive treatment is prepared. A useful second opinion should explain the sequence, alternatives and logistical feasibility, not simply supply another list of drugs.