Significant advances in the diagnosis and treatment of large B-cell lymphoma have driven the development of new guidelines, published in the British Journal of Haematology.

In a key change from the last iteration in 2016, the 2024 guideline has been split into two separate guidance documents as clinical management, diagnostic aspects, and treatment options have become increasingly complicated, lead author Professor Chris Fox, Consultant Clinical Haematologist at Nottingham University Hospitals NHS Trust, UK, told the limbic.

The first of these to be published concerns newly diagnosed and first-line treatment of LBCL [link here], while the second, to be published later this year, will advise on relapsed or refractory disease and subsequent lines of therapy.

With regard to diagnosis, clinical haematologists should be aware that invasive procedures such as bone marrow biopsies are now no longer necessary in most patients because of improved imaging, such as PET CT, “which is now widely available and very important for accurate staging”, Professor Fox noted.

According to the guideline, “PET-CT is more likely than bone marrow biopsy to detect marrow involvement with LBCL, and the presence of non-avid bone marrow disease does not confer a worse prognosis”.

“Bone marrow biopsy may be considered for selected patients in whom a co-existing haematological condition is suspected (e.g. low-grade lymphoma or myelodysplasia), and where this would inform clinical management, but is otherwise unnecessary”.

The guideline also outlines additional genetic tests that can be performed in patients as part of initial risk assessment, such as FISH for MYC and BCL rearrangements.

“MYC translocation to an immunoglobulin partner is most strongly associated with inferior overall survival,” the authors noted, but other predictors of poor outcome such as TP53 mutations and ‘molecular high-grade’ gene expression signature “are not yet routinely used in clinical prognostication,” they said.

Management

On the treatment side, the guideline includes more detailed advice on how best to manage stage one and stage two disease, and the patients potentially eligible for more limited treatment and less chemotherapy, as guided by PET scanning.

Of note, polatuzumab vedotin in combination with chemotherapy has been newly added as a treatment option for patients with certain risk factors.

Six cycles of RCHP-polatuzumab vedotin is an endorsed option for patients aged under 80 years with stage I/II disease and an IPI prognostic score of two or more.

In patients with primary extra-nodal LBCL, RCHP-polatuzumab vedotin can be considered for patients who are considered fit for full-dose chemotherapy with an ECOG PS score of 0-2 and an IPI of 2-5.

And for advanced stage disease, the guideline authors recommend six cycles of RCHP-polatuzumab vedotin as first-line option for patients with de novo LBCL, who are fit for full-dose chemotherapy and have an ECOG PS ≤ 2 and an IPI score of 2–5.

An accompanying Commentary [link here] by Dr Chathuri Abeyakoon and Dr Gareth Gregory from the Lymphoma Research Group at Monash University and Monash Haematology, said newly diagnosed DLBCL remains an active space for new drug development.

They said the next phase of investigation includes R-CHOP combined with bispecific antibodies, tafasitamab/lenalidomide, Bruton tyrosine kinase inhibitors and cereblon E3 ligase modulators.

“Early use of CAR-T cell transplantation for high-risk patients or those failing up-front therapy at interim response assessment is likely to inform new optimised treatment strategies.”

“However, rational use of new treatments demands the implementation of improved diagnostics and monitoring of patients on therapy.”

They also said the pharmacoeconomic and therapeutic toxicity of new therapies needs to be mitigated through biomarker response-adapted strategies to minimise therapeutic exposure wherever this can safely be performed.

According to Professor Fox, the guideline “provides a comprehensive and detailed summary of all the progress that has been made in diagnosing, staging and managing LBCL since the last guidance document was published”.

“There’s also a huge amount of background work behind the guideline which is reflected in all the references, so it also offers information and guidance on further reading,” he added.