Lymphoma research: update

Chronic lymphocytic leukaemia (CLL)

Dr Satyen Gohil, University College London Hospitals and Dr Piers Patten, King’s College Hospital, London, discussed the current research in CLL.

• The immunoglobulin heavy chain (IGHV) gene continues to provide useful information in terms of how patients will respond to front line treatment.
• In the FLAIR clinical trial, patients with mutated IGHV, who overall have a better response and outcome, take longer to reach a level of minimal residual disease (MRD) compared with those with unmutated disease. This suggests that achieving MRD might be less important for patients with mutated IGHV.
• MRD testing is not currently routinely available on the NHS outside of clinical trials but ongoing trials looking at making better use of MRD will provide further guidance in the future.
• With increasing treatment options, a key consideration is having the time for patients and doctors to discuss the advantages and disadvantages of each approach. With the high treatment response rates seen, quality of life measures will help guide future selection of treatment.
• In contrast, additional treatment options are needed for patients with refractory disease. Updated data on the use of bispecific antibodies, non-covalent BTK inhibitors, BTK degraders and CAR-T cell therapy is promising but further study is needed.

Mantle cell lymphoma

Dr Toby Eyre, Oxford University Hospitals, described how treatment of mantle cell lymphoma using BTK inhibitors was a particular focus of the Annual Meeting.

• A number of studies indicate that a combination of antibody therapy with a BTK inhibitor could be a potential new ‘standard of care’ option for older patients.
• The ENRICH study explored treatment with ibrutinib and rituximab.
• The ALTAMIRA study looked at treatment with acalabrutinib and rituximab.
• The OASIS-II study showed that the addition of a BCL2 inhibitor might further improve the response but adds toxicity.
• Studies indicate that an autologous stem cell transplant is not needed if treatment with a BTK inhibitor is available, or if undetectable MRD is achieved.
• Analysis of data confirm that maintenance therapy with rituximab remains a critical part of the treatment of mantle cell lymphoma.

Follicular lymphoma

Dr Emil Kumar, King’s College Hospital, London, discussed expanding options for treating relapsed and refractory follicular lymphoma.

• Long-term results from clinical trials looking at T cell redirecting therapies (bispecifc antibodies and CAR-T cell therapy) are promising and we await approval for their use in the NHS.
• Several trials, including the UK REFRACT study, are testing the use of bispecific antibodies earlier in treatment lines and in combination with other drugs. Useful data is emerging, exploring factors such as the impact of prior treatments, toxicity and deliverability.
• The role of stem cell transplant requires regular re-appraisal in this changing therapy landscape; but currently remains a useful treatment option for some patients in the UK.
• The potential for response-adapted therapy is being explored in further studies (PETReA, FOLL19), aiming to ensure the right balance of toxicity and benefit for each patient.

Central nervous system (CNS) lymphoma

Dr Kate Cwynarski, University College London Hospitals, on challenges around treating the CNS lymphomas.

• There are three types of secondary CNS lymphoma:

- de novo – lymphoma in both the CNS and systemically at diagnosis

- isolated – relapse with lymphoma only in the CNS

- synchronous – relapse with lymphoma in the CNS and systemic disease.

• The patterns of relapse and treatment outcomes differ by type, therefore this must be taken into account for optimal management and treatment choice.
• Systemic relapse is rare for patients presenting with isolated relapse supporting approaches used for primary CNS lymphoma.
• Thiotepa autograft appears to provide durable remissions in a significant proportion of patients with secondary CNS lymphoma who achieved a good response after induction chemo- immunotherapy.
• Early results from an observational study in the US support the use of CAR-T cell therapy as an option in patients with relapsed or refractory large B cell lymphoma with secondary CNS lymphoma, but long-term durability is less clear.

Hodgkin lymphoma

Professor Graham Collins, Oxford University Hospitals, presented the research in the field of Hodgkin lymphoma.

• The biology of Hodgkin lymphoma in older patients is different to that of younger patients. Understanding this could impact treatment decisions.
• Results from the GHSG HD21 trial indicate that the treatment regimen BrECADD (brentuximab vedotin, etoposide, cyclophosphamid, doxorubicin, dacarbazine, dexamethasone), guided by PET scans, gives good response rates in older patients with advanced disease. Ensuring balance between efficacy and tolerability will be important.
• Long-term outcomes for patients with early stage, low risk disease are excellent irrespective of the use of radiotherapy.
• Additional data supports a reduction in the use of bleomycin in the treatment of early stage as well as advanced stage disease.
• For advanced stage lymphoma, interim response assessment might be improved by using a measurement called ‘metabolic tumour volume’.
• Studies continue to evaluate the role of checkpoint inhibitors. Autologous stem cell transplant remains the standard of care for most patients with relapsed disease.

Diffuse large B cell lymphoma (DLBCL)

Professor Chris Fox, Nottingham University Hospitals, reported that recent DLBCL research supports current UK treatment practices.

• The 5-year extended follow-up of the POLARIX study confirms Pola-R- CHP (polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin and prednisolone) as standard of care for intermediate and high-risk DLBCL.
• The COALITION study suggests that the addition of glofitamab to standard therapy for younger patients with high-risk DLBCL is feasible and delivers promising survival outcomes. Large trials are underway in a wider patient population.
• Long-term results from the EPCORE NHL-2 trial suggest that treatment with epcoritamab plus R-CHOP has a high curative potential in patients with high-risk DLBCL, supporting the ongoing phase 3 clinical trial.
• Results from EPCORE DLBCL-3 suggest that treatment with epcoritamab is a promising chemotherapy-free option for older patients with newly diagnosed DLBCL who may be unable to tolerate anthracycline -based regimens.
• Early results support further trials of fixed-duration treatment with glofitamab and englumafusp alfa for relapsed and refractory disease.