RATHL trial: Reducing serious side effects and improving outcomes

Recently published findings from the phase 3 RATHL trial (Response-adapted therapy for advanced Hodgkin lymphoma) show that most people can be spared some side effects.

Image of lots of blood vials with different coloured caps

In the trial, a PET scan given after 2 cycles of standard ABVD chemotherapy was used to decide what further treatment people needed. People with a good response (PET negative) were randomised  either to continue ABVD or to receive AVD with bleomycin (B) being omitted. People who didn’t respond well (PET positive) were given more intensive chemotherapy – BEACOPP.

Dropping bleomycin for good responders after 2 cycles of ABVD reduced side effects.

Bleomycin has been used as part of the ABVD regimen for Hodgkin lymphoma for 30 years. However, it can cause long-term lung damage.

The trial results suggest that dropping bleomycin and continuing with AVD in those who are responding well is safer but just as effective.

  • 937 people had a negative PET scan after 2 cycles of ABVD. Half were randomised to receive 4 more cycles of ABVD and the other half to receive 4 cycles of AVD.
  • The vast majority of people (more than 19 in every 20 people) in both groups were still alive 3 years after completing treatment: 97.2% of those who had more ABVD and 97.6% of those who had AVD.
  • The vast majority of people (more than 17 in every 20 people) in both groups were still in remission 3 years after completing treatment: 85.7% of those who had more ABVD and 84.4% of those who had AVD.

People who stopped having bleomycin were less likely to have serious side effects in their lungs, although this was rare in both groups (less than 1 in 20 people).

There is an urgent need to identify people who need more intensive or different treatment for their Hodgkin lymphoma.

More intensive chemotherapy for poor responders after 2 cycles of ABVD could improve their outcome.

BEACOPP could be more effective than ABVD for some people with Hodgkin lymphoma. However, it causes more side effects, both immediate and long-term. It is also more likely to cause infertility, low blood counts and infections than ABVD.

In the RATHL trial, PET scans were used to identify people who need more treatment early, giving them a better chance of being treated successfully. If the PET scan showed significant lymphoma, escalating those people to a stronger chemotherapy regimen gave a better chance of remission.

  • 172 people had a positive PET scan after 2 cycles of ABVD so received BEACOPP.
  • Around 9 in every 10 people (87.8%) were still alive 3 years after completing their treatment
  • Most people (around 7 in every 10; 67.5%) were still in remission 3 years after completing their treatment.

This part of the study was not randomised so it can’t be certain that BEACOPP gave better results than continuing with ABVD. However, the survival rates were good compared with other studies.

‘Knowing which patients have a more difficult to treat form of the disease means we can select those who need stronger chemotherapy, while sparing everyone else the severe side effects such as infertility. This approach, along with a reduction in the need for radiotherapy, should substantially reduce damage to healthy tissues and the risk of second cancers caused by treatments.’
Professor Peter Johnson, University of Southampton, Chief Investigator for the study.

Changing practice now and in the future

These are important findings and many centres are already using interim (part-way through treatment) PET scans to guide them on what treatment would be best for each person.

The good news is that the majority of people diagnosed with Hodgkin lymphoma can be cured –  in this trial more than 95 per cent of patients are alive after three years. But we worry about the long-term side effects from the treatments we use. As we’ve done in this trial, personalising treatment based on how well it works is a major development for patients with Hodgkin lymphoma, and sets a new standard of care.
Professor Peter Johnson

There are still plenty of questions to answer in future trials. These trials will help to further define who needs more intensive treatment and what the best treatment is. More effective initial treatment, perhaps including newer drugs, might help to reduce the number of people who need more intensive treatment. New drugs might also improve results for people who don’t respond well to initial treatment  and could spare everyone some of the serious side effects of treatment.

Search our database now to see what trials are open for people with Hodgkin lymphoma.

Results of the RATHL trial were published in the New England Journal of Medicine on 23 June 2016. The full article is available at: http://www.nejm.org/doi/pdf/10.1056/NEJMoa1510093 (Accessed July 2016).

Prof. Johnson’s quote was taken from the press release by Cancer Research UK: http://www.cancerresearchuk.org/about-us/cancer-news/press-release/2016….