Clinical Trials
Highlights from ASH
The American Society of Haematology’s 65th Annual Meeting took place in San Diego in December. We recently attended a meeting in London presenting the conference highlights to hear experts in the field describe the latest developments in lymphoma.
The meeting showcased the wide range of exciting research taking place in all areas of lymphoma. Presentations covered updates on trials of promising new treatments as well as ways to optimise the use of current treatments. With a growing range of treatment options available, studies are giving insights on how to determine which treatment is best for each individual patient and when.
Low-grade lymphoma
Professor Jessica Okosun (Barts Cancer Institute) presented the latest advances in the use of molecular tools. Studies are looking at how these tools can be used to predict which patients will benefit from particular treatments.
- A form of liquid biopsy called ‘ctDNA’ could:
- act as an alternative to tissue biopsy in some circumstances
- provide an insight as to who is likely to respond to treatment
- test responses to novel therapies
- help identify those at risk of secondary CNS lymphoma.
- Molecular tools could help to optimise the use of CAR-T cell therapy by helping to predict who will respond, testing if adding additional drugs can improve outcomes, and monitoring for long-term complications.
Dr Toby Eyre (Oxford University Hospitals) gave an overview of recent research on mantle cell lymphoma.
- Data shows that disease progression within 2 years of treatment is a strong indicator of poor outcomes, highlighting the need for further treatment options for these patients.
- Clinical trials suggest that new treatment combinations (rituximab, bendamustine and cytarabine followed by venetoclax, and zanubrutinib combined with venetoclax and obinutuzumab) may be effective, although further work needs to be done to define who will benefit most.
- The SYMPATICO study (including patients in the UK) indicates that addingvenetoclax to ibrutinib can improve outcomes for people with relapsed or refractory disease compared to treatment with ibrutinib alone, although some side effects were more common.
Chronic lymphocytic leukaemia
Dr Helen Marr (Newcastle upon Tyne Hospitals) discussed first-line treatment of Chronic lymphocytic leukaemia (CLL). Trials have provided further insight into treatment with ibrutinib and venetoclax:
- The FLAIR study (a flagship UK clinical trial) indicates that determining the duration of treatment based on ‘measurable residual disease’ can maximise treatment response. The challenge is how to use this approach in the NHS.
- Longer term follow-up of the GLOW study (patients over 64 years or with comorbidities) indicates that treatment with ibrutinib and venetoclax is still superior to chlorambucil plus obinutuzumab 55 months after treatment.
- The CAPTIVATE study (patients under 70 years) shows promising responses in patients needing subsequent therapy following fixed-duration treatment.
- Initial studies of sonrotoclax, a new second-generation BCL2 inhibitor, in combination with zanubrutinib, show promising results.
Dr Sunil Iyengar (Royal Marsden Hospital) focused on relapsed and refractory CLL.
- Extended follow-up of the ALPINE trial indicates continued improved outcomes following treatment with zanubrutinib after 3 years. Zanubrutinib is now available in the UK.
- The CAPTIVATE study shows promising responses to ibrutinib -based retreatment in those with progressive disease after first-line fixed duration treatment with ibrutinib and venetoclax.
- Studies are also looking at treatment options when disease progresses following treatment with BTK inhibitors and venetoclax. Promising results were reported for pirtobrutinib from the BRUIN study and lisocabtagene maraleucel (a CAR-T cell therapy) from the TRANSCEND CLL trial.
High-grade lymphoma
Dr Wendy Osborne (Newcastle upon Tyne Hospitals) reported on diffuse large B-cell lymphoma (DLBCL) research.
- In first-line treatment, the use of radiotherapy to treat primary mediastinal lymphoma could be avoided in a group of patients responding to chemoimmunotherapy. Further study into identifying this group is required.
- For second-line treatment, studies are comparing responses to autologous stem cell transplant (SCT) and CAR-T cell therapy to determine which is the best approach in a variety of situations. Comparisons are difficult with the available data.
- For third-line treatment, many new options have recently been approved. Studies are focussing on identifying suitable patients, determining how long treatment responses last and the order to sequence treatment options.
Dr Osbourne also presented the latest data on whether CAR-T therapy is an effective treatment option for secondary central nervous system (CNS) lymphoma. Current studies have given mixed results, indicating that more research is required.
Hodgkin lymphoma
Professor Graham Collins (Oxford University Hospitals) gave an overview of recent Hodgkin lymphoma research.
- Patients over 60 years of age often have worse outcomes than younger patients. The SWOG S1826 study illustrates that treatment with nivolumab-AVD gives significantly better results compared with brentuximab vedotin-AVD and could be a major improvement for this group.
- Biological insights might explain the difference in treatment response rates by age. Two molecular Hodgkin lymphoma subtypes have been discovered, and the frequency of each differs with age. The molecular subtype might also affect the impact of specific treatments.
- Long-term follow-up of the RATHL study indicates that bleomycin affects lung function for at least 5 years after treatment. This is important when discussing what may happen in the longer term after treatment.
- Clinical data indicates that PD1- based treatment before autologous SCT improves outcomes compared to treatment with brentuximab vedotin or chemotherapy-based treatments. This will be explored in UK trial data and could impact decision making.
CAR-T cell therapy
Dr Andrea Kuhnl (King’s College Hospital London) gave an update on CAR-T cell therapy research.
- Real-world data for CAR-T cell therapy are encouraging, matching the results of clinical trials.
- Studies are focussing on patient management, such as the use of different bridging therapies, and whether prophylactic therapies can prevent neurotoxicity. These are highly relevant to guide use of CAR-T cell therapy in the UK.
- Research is exploring the use of biomarkers to predict treatment failure, for disease surveillance and to develop prognostic scores to predict patient outcomes.
Waldenström’s macroglobulinaemia
Dr Helen McCarthy (Royal Bournemouth Hospitals) and Dr Shirley D’Sa (UCLH) reviewed developments in Waldenström’s macroglobulinaemia (WM).
- A new prognostic model has been developed to help predict clinical outcomes.
- Studies are focussing on which BTK inhibitors to use and when, if outcomes can be improved by combining with other treatments, and which treatments to use following relapse.
- Analysis of data from ibrutinib- tolerant patients a year or more after initiation of zanubrutinib indicates that outcomes were maintained or improved, and treatment was well tolerated. Zanubrutinib is available on the NHS in relapsed disease.
- Good outcomes following CAR-T cell therapy have been reported for patients with refractory/relapsed transformed WM, although this is not currently available in the UK.
With thanks to Professor Graham Collins for reviewing this information.
