Medical opinion
40 years of lymphoma
As Lymphoma Action comes to the end of its 40th anniversary year, we wanted to reflect on changes in treatment and care, and look forward to what treatment might look like over the next 40 years.
We spoke with Professor Andy Davies, Professor of Haematological Oncology at the University of Southampton and Dr Cathy Burton, Consultant Haematologist at Leeds Teaching Hospital in a recent podcast. Full details of how to listen to the podcast are at the end of the article.
Diagnosis
Historically the diagnosis of lymphoma was very much based on morphology (the study of form and structure) to try and define certain subtypes of lymphoma. But there were only three major entities; high-grade lymphoma, low-grade lymphoma and Hodgkin lymphoma. This was based mainly on the presence of Reed-Sternberg cells, indicating Hodgkin lymphoma, or the absence of them indicating non-Hodgkin lymphoma. Today over 100 different subtypes are described.
As time has gone on, what’s really changed is the number of tests we can do on each patient’s individual biopsy sample including immunohistochemistry and genetic studies. It has expanded beyond the pathologist to bioinformatics which use computers, maths and statistics to analyse large sets of biological data. With this, we can gain diagnostic information, which is important to be able to treat the patient in the most effective way. In addition, we can gain prognostic information, giving us information on how a patient might respond to certain types of treatment. Add to that the introduction of CT and PET/CT scanners, which have become a key part of staging and managing treatment.
Treatment
Looking back to the 1980s and 1990s, treatment had more of a ‘one size fits all’ approach. It was a fairly blunt approach, using chemotherapy for non-Hodgkin lymphoma and radiotherapy for Hodgkin lymphoma, adding chemotherapy if it was needed.
Much larger fields of radiotherapy were used in the past, resulting in potential long-term effects. In addition, the chemotherapy used to treat Hodgkin lymphoma was really quite toxic. The chemotherapy for non-Hodgkin lymphoma was CHOP which, although it is 50 years old, is still the backbone of much of what we use today.
“There have been some really major changes over the past 40 years. A key development has been the introduction of targeted therapies. These are medicines that have been designed to ‘target’ cancer cells by attacking particular proteins on lymphoma cells like a ‘magic bullet’.
Targeted treatments attack lymphoma cells more precisely than chemotherapy. This means they can kill lymphoma cells with fewer effects on healthy cells, leading to potentially fewer side effects.
The introduction of rituximab in the late 1990s had a big impact in B-cell lymphomas. Rituximab is a type of targeted treatment called antibody therapy and was the first of its type to be described and approved.
We soon discovered that when we added targeted therapies to chemotherapy, it improved the number of people who were responding to chemotherapy. It has really been a kind of revolution for us.
More recently, there has been the development of bispecific antibodies. These work in a similar way to targeted treatments in terms of activating a person’s own T cells but instead of sticking to one target protein, bispecific antibodies stick to two different target proteins; one on lymphoma cells and one on healthy T cells (immune cells that can kill other cells). This helps the T cells find and destroy the lymphoma cells. We’re seeing trials at the moment looking at incorporating bispecific antibodies much earlier into treatments. This is revolutionising the treatment of high-grade lymphoma and is becoming available for some of the low-grade lymphomas, such as follicular lymphoma.
Although bispecific antibodies are not necessarily completely free of toxicity, they don’t have the classical side effects we associate with chemotherapy like hair loss, mouth ulcers and high infection rates.
The technology behind radiotherapy is marching on hugely and we’re seeing the use of much smaller radiotherapy fields and better delivery techniques with significantly less toxicity.
Although the majority of people with lymphoma don’t need to have a stem cell transplant, the technology around this has also really moved on. The effectiveness of stem cell transplantation has improved and how we support patients through this type of treatment has been really important.
We now also have CAR-T cell therapy where we can engineer the patient’s own T cells outside of the body to recognise the lymphoma cells and directly kill them. And there’s more research taking place to make CAR-T cells better, safer, and to perhaps use them in some types of lymphoma earlier in the disease course. This has been a massive landscape-change in some types of lymphoma.
Personalised medicine
A crucial change has been trying to understand better the underlying changes within an individual patient’s tumours so that we can better target our therapy to an individual. Our aim, probably over the last 10–15 years, has been the development of this personalised medicine.
“It is important that we, as healthcare professionals, consider all options. We have very much a team-based approach to managing patients. So, patients are all discussed through a multidisciplinary team meeting where we look at the pathology, the radiology and all the clinical information.
And then the most important thing is informing the patient and making a shared decision between ourselves as clinicians and the person with lymphoma.
We have a vast number of treatments now and it’s about using them in the right order. For some lymphomas treatment is curative and it’s all about first-line treatment and trying to cure upfront. For other lymphomas, they really are a chronic disease and it’s all about managing that by reducing the toxicity as much as possible, but at the same time giving effective treatment.
Looking forward to the next 40 years
One of the key things we want to do is improve the effectiveness of the treatments we have. Importantly, we want to make sure that we can deliver treatments with minimal side effects. We also worry about potential long-term side effects and want to reduce those.
And really important is focussing on people living well after having had treatment for lymphoma; we sometimes use the term ‘survivorship’.
“But looking after patients for the rest of their lives, in terms of reducing any long-term complications of therapy, is crucial. And that’s not only physically, but also providing any psychological support that people need.
Treatment and care outside the hospital setting
It’s also worth considering treatment and care moving into the home setting, which is much better for patients and means we are not using so many hospital beds. We’re already moving in this direction for example with chemotherapy, CAR-T cell therapy and transplantation, using ambulatory care services (care received without staying overnight in hospital; sometimes in local accommodation or at home). This approach would also work well with targeted treatments.
Does artificial intelligence (AI) have a place in the healthcare system?
We should embrace AI in terms of where it can support what we do. It’s not going to replace clinical staff, but there are elements of AI that could actually improve delivery of care and save a lot of time so increasing efficiency. For example, AI might be able to be used to speed up the diagnostic pathway or predict how patients might respond to treatment.
Can the NHS cope with all these changes?
Doctors, nurses and other allied health professionals are used to a changing field and as a clinical body they are supported as new treatments are introduced.
As more and more sophisticated treatments come along, undoubtedly it’s a challenge for the NHS. But the NHS is remarkably flexible and adaptable. It has already been challenged, for example with the introduction of CAR-T cell therapy. Probably 15 years ago we would never have imagined that a therapy like that could have been incorporated into routine NHS care, but it has very successfully.
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