Which antibody to use first-line for follicular lymphoma?

The great obinutuzumab debate: which antibody to use first-line for follicular lymphoma?

It can take a very long time to find out which treatment is best for a condition that has a long average survival time, like follicular lymphoma.

Rituximab in combination with chemotherapy is standard treatment for people with advanced follicular lymphoma who need to start treatment. Obinutuzumab is a newer antibody that targets CD20, the same target as rituximab.

Evidence from clinical trials suggests that obinutuzumab might be slightly more effective than rituximab, but this increases the side effects of treatment. So, should obinutuzumab be used as part of the first treatment for follicular lymphoma, or should we stick with rituximab? This issue was the subject of a debate at the recent Current Perspectives in Haematological Malignancies meeting in London in July.

What are the benefits of obinutuzumab?

There is a small increase in the length of remissions (lymphoma is under control) with obinutuzumab compared with rituximab, regardless of what chemotherapy it is used with.

Remissions appear to be deeper, with more people having undetectable levels of lymphoma after obinutuzumab than rituximab.

Fewer people relapse within 2 years of their treatment if they have obinutuzumab compared with rituximab. Relapsing within 2 years is usually an indication that your lymphoma is more difficult to treat than usual.

And the drawbacks?

Despite the apparent benefits, there is not yet any evidence that obinutuzumab can help you live longer than rituximab, just that you stay in remission for longer. Your lymphoma can still be treated if it comes back.

Having obinutuzumab instead of rituximab does not seem to improve your quality of life. Some of the side effects of obinutuzumab, such as infusion reactions , can be uncomfortable and frightening, even if they are generally treatable.

You can’t have obinutuzumab subcutaneously (by injection under the skin) at present, so you’d have to spend longer in hospital to have it intravenously (by drip) than you would if you could have subcutaneous rituximab. This also increases costs.

We don’t yet know the long-term effects of obinutuzumab as it is newer than rituximab.

Obinutuzumab is approved to be used both first-line and for people whose lymphoma comes back soon after having rituximab. This gives the options of having obinutuzumab first-line if you have moderate to high risk follicular lymphoma, or keeping it in reserve so you can have obinutuzumab with bendamustine as a second-line treatment if you have already had rituximab. The decision is likely to come down to your individual circumstances and the treatment options available.

Evidence continues to be collected about the longer-term effects of obinutuzumab and this may help to settle the debate in the future.

With thanks to Dr Graham Collins and Dr Wendy Osbourne for reviewing this article.