The idea of reducing treatment for Hodgkin lymphoma to reduce side effects, without reducing the effectiveness of the treatment, is a topic discussed at every major lymphoma meeting. The annual meeting of the British Society of Haematology (Liverpool, April 2018) was no exception.
Results from the HD18 trial were presented at the meeting. These have been previously reported at international meetings and published in The Lancet. The escalated BEACOPP chemotherapy regimen works well as a treatment for Hodgkin lymphoma, and is often used for people with lots of factors that mean their lymphoma might be difficult to treat (‘risk factors’). The downside is that escalated BEACOPP causes more serious side effects than the other standard regimen for Hodgkin lymphoma, ABVD. HD18 showed that people who respond well to the first 2 cycles of escalated BEACOPP do just as well if they have only 2 more cycles instead of the usual 4 or 6 more cycles. Importantly, a total of 4 cycles causes fewer side effects than 6 or 8 cycles.
More debatable were the results of the ECHELON-1 trial, which were presented and have been published in another important journal, the New England Journal of Medicine. This trial tested whether bleomycin (the ‘B’ in ABVD chemotherapy) could be replaced with the targeted drug brentuximab vedotin. After 2 years’ follow-up, more people in the brentuximab and AVD chemotherapy group were still in remission (no evidence of lymphoma and no more treatment needed) compared with the standard ABVD group (82% versus 77%).
Clinicians are divided on whether brentuximab should be used as part of first-line treatment. This was the subject of a lively debate at the Current Perspectives in Haematological Malignancies meeting in London in July.
While using brentuximab instead of bleomycin reduces lung toxicity and gave a small increase in the amount of people achieving a remission, one problem seems to be that a full course of ABVD was used in the ECHELON-1 study. Results from the UK RATHL trial - support the idea that bleomycin can be dropped from ABVD after 2 cycles in people who are responding well to treatment, reducing the lung toxicity associated with this treatment. Adding brentuximab vedotin increases side effects like neutropenia (low white blood cell counts that can increase your risk of infection) and peripheral neuropathy (nerve damage). Newer targeted drugs like brentuximab vedotin also increase the costs of treatment dramatically.
A recent letter published in Blood journal questions the methods used in ECHELON-1. An unusual outcome measure was used, which makes it difficult to interpret and reproduce the results of the trial.
There is still debate over the best time to use brentuximab vedotin for treatment of Hodgkin lymphoma. The general feeling was that while some advocates of ECHELON-1 might argue that there could be a role for using brentuximab first-line in people with high-risk Hodgkin lymphoma, such as those with stage 4 (widespread) lymphoma, others suggest that it might be better to follow the approach used in HD18 and continue to use brentuximab for people who relapse.
There is not a correct answer regarding which treatment path to follow. In Germany, the overall success of the treatment in curing the disease is prioritised, but this risks more side effects for some people who might have been cured with less intensive treatment. In the UK, it has been usual to use the strongest treatment only in those people at highest risk of their Hodgkin lymphoma failing to respond to treatment or relapsing. However, this may be changing as shorter courses of intensive treatment are shown to be effective for many.
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With thanks to Dr Andrew McMillan, Consultant Haematologist, Nottingham University Hospitals NHS Trust for reviewing this article.