Evidence
Alert

Rituximab improves survival in children with non-Hodgkin’s lymphoma

Children with an aggressive cancer of the lymphatic system may benefit from a new treatment regime. New findings from an international trial show that adding a drug called rituximab to standard doses of chemotherapy significantly improves young people’s survival.

Non-Hodgkin’s lymphoma is a cancer that develops in the lymphatic system, a network of vessels and glands spread throughout the body. Clear fluid called lymph carries infection-fighting white blood cells (lymphocytes) through the lymphatic system. Most non-Hodgkin’s lymphoma occurs when a type of white blood cell (B cells) multiply in an abnormal way.

Following the study, regulators in Europe have approved rituximab for use in children with high-risk, mature B-cell non-Hodgkin’s lymphoma.

This successful trial builds on decades of progress in cancer treatment for children. In the 1980s, fewer than one in three children with this type of cancer were cured. Scientists now need to find ways to reduce side-effects and toxicity of the drug.

What’s the issue?

Chemotherapy is an effective treatment for most children with B-cell non-Hodgkin’s lymphoma, but about 15% of these young patients sicken again and often die.

Rituximab is a relatively new drug that works on the immune system. It attacks the B cells that drive non-Hodgkin’s lymphoma. It has previously been shown to improve survival in adults with the disease.

Before this study, there was little data on rituximab in children. That is partly because the disease is relatively rare in children and it has been difficult to conduct a clinical trial. It is also because children tend to do better on chemotherapy alone than adults, and rituximab can have toxic side-effects.

What’s new?

In this randomised trial, half the children and young people (164), all aged under 18, received six doses of rituximab alongside standard chemotherapy. The others received chemotherapy alone. The study assessed side effects and overall survival after three years.

The results showed that rituximab added to standard chemotherapy significantly increased survival:

  • almost all of those (94%) given rituximab survived for three years, compared with four in five (82%) of those who received chemotherapy alone

However, rituximab also increased the risk of side-effects:

  • one-third (33%) of those given rituximab had severe side effects, including fever, infection and inflammation of the mouth and lips. This compared with one in four (24%) of those who received chemotherapy alone.

Why is this important?

The results raise the cure rate for this aggressive childhood cancer to 94%. That means three times as many children survive compared to just 40 years ago. The results were so positive that the comparison was halted earlier than planned, and all enrolled children were given rituximab.

The study also shows the value of international collaboration. It recruited more than 300 young patients from Europe, North America and Asia in order to ensure meaningful results.

What’s next?

Regulators in Europe approved rituximab for treating this childhood cancer in March 2020. Combined with chemotherapy, it has become recommended care.

Researchers now want to optimise the dose. About half the children who died after being given the combined treatment in the trial had suffered toxic side-effects. Reducing the number of times patients are given the drug could reduce that risk.

You may be interested to read

The full study: Minard-Colin V, and others. Rituximab for high-risk, mature B-cell non-Hodgkin’s lymphoma in children. New England Journal of Medicine. 2020;382:2207-2219

European Medicines Agency (EMA) Rituximab Assessment Report, 2020

Information from Cancer Research UK: Diffuse large B cell lymphoma

Funding

This project was funded by the French Ministry of Health, Cancer Research UK, NIHR Clinical Research Network, Children’s Cancer Foundation Hong Kong, US National Cancer Institute and Hoffmann-La Roche-Genentech.

Commentaries

Study author

When I saw the results, I just thought wow! They are really good news and they have already changed practice. I am so happy for the children. Everyone should know about this because it’s important that we talk about cancer in children. People often seem surprised that children can suffer from these serious cancers. The more they know, the more they will support our research.

The way we did this trial – an academic sponsor with pharma support and international collaboration – is a really good model. We have learned that we can work together and that good things happen when we do.

Veronique Minard-Colin, Childhood Cancer Specialist, Gustave Roussy Cancer Campus, Villejuif, France

Researcher

The results of the trial have had an immediate impact on clinical practice with the adoption of rituximab in addition to chemotherapy for children with high risk disease. However, this is a simplistic message. Chemotherapy for B-cell non-Hodgkin’s lymphoma is already very intensive and the addition of rituximab adds to this.

There are two outstanding questions. First, what is the long-term impact of rituximab on children treated for this cancer? Second, how do we treat those who still relapse after treatment with rituximab? There is an urgent need to identify biomarkers that can predict which patients will still relapse and to understand what is driving the tumours’ resistance to treatment.

Vikki Rand, Professor of Biosciences, School of Health and Life Sciences, Teesside University, Middlesborough

Conflicts of Interest

Some authors have received fees and funding from various pharmaceutical companies.