Immune therapy can delay progression in type of lymphoma by almost a decade

Newly reported updated results of a study from UCLH and UCL highlights the powerful benefits of a targeted immune therapy for a type of slow-growing blood cancer.

The findings show that the drug rituximab can slow disease progression and delay the need for chemotherapy for patients with low tumour burden follicular lymphoma. For patients who received rituximab, the average time before they needed further treatment was more than 15 years, compared with just under six years for patients not receiving the drug. It means the drug can offer a delay of approximately 10 years in time before chemotherapy is needed.

Previously reported results of the study also showed the drug has few side effects.

Follicular lymphoma is a slow-growing type of lymphoma, a blood cancer in which white blood cells multiply uncontrollably.

In its early stages, many patients are not symptomatic, and there is no benefit to starting chemotherapy until symptoms start. For this reason, the standard of care has been active observation without treatment, often referred to as ‘watchful waiting’.

The study, led via the UCL Cancer Trials Centre, and published in The Lancet Haematology – looked at whether immune therapy with rituximab can delay symptom progression, and therefore delay the need for chemotherapy which is often associated with significant side effects.

The study began in 2004 and involved 455 patients from 188 centres across five countries. Patients were followed for 15 years.

The study, supported by the NIHR UCLH Biomedical Research Centre, compared three approaches:

• ‘Watchful waiting’ – the current standard of care
• A short dose of rituximab (four weekly doses) – known as an induction dose
• The same induction dose, followed by ‘maintenance’ doses every two months for two years.

The goal was to see how long each group could go before needing chemotherapy.

After 15 years, 65% of patients in the rituximab maintenance group had not needed chemotherapy, or other additional treatment.

This compares with 48% of patients who received the short, induction dose of rituximab, and 34% in the watchful waiting group.

Expressed in another way, patients in the watchful waiting group needed additional treatment after an average of 5.6 years. This compared with 14.8 years in the induction dose group.

The average time before treatment is needed in the induction and maintenance group will be even longer. It could not be estimated from the study, because after 15 years of follow-up, two-thirds of patients were still doing well and did not require further treatment.

The trial findings support earlier results from the trial a decade ago suggesting that rituximab could delay the need for chemotherapy. But because low tumour burden follicular is often a slow-growing cancer, researchers needed to follow patients for a long period in order to fully understand the impact of the treatment and to be able to report these final results, in particular to ensure that giving patients rituximab earlier than normal did not impact negatively on their subsequent responses to chemoimmunotherapy and overall survival.

Consultant haematologist at UCLH Dr Michael Northend, who is first author of the paper, said: “Our study highlights that rituximab can substantially delay the need for further treatment, typically chemotherapy, for patients with low tumour burden follicular lymphoma.

“The study is clear that rituximab, especially when followed by maintenance therapy, can offer patients many more years without needing chemotherapy – and does this with minimal toxicity. This could be a huge benefit in terms of quality of life for patients.

“The results also suggest that some patients who receive rituximab may avoid the need for chemotherapy altogether.”

The chief investigator of the study is consultant haematologist Dr Kirit Ardeshna, a specialist in lymphoma at UCLH.

Dr Ardeshna said: “It’s great to see the final paper published. Is the culmination of over 20 years of work and is a fantastic achievement for all those involved. The results we have generated will help clinicians discuss treatment options with their patients who can then decide the option best suited to their personal circumstances.”

The study was funded by Cancer Research UK, Lymphoma Research Trust, Lymphoma Association, and Roche.

Dr Northend is interviewed on a podcast from The Lancet Haematology discussing the results of the study. Listen to the podcast.