People with advanced-stage Hodgkin’s lymphoma can be spared the serious side effects of chemotherapy thanks to high-tech scans that predict early response to treatment, new findings by University of Sydney scholars in collaboration with national and international partners reveal.
Published in The New England Journal of Medicine, the authors report that patients who received standard chemotherapy without continued use of the drug Bleomycin had the same survival rates as those who received standard chemotherapy with this drug. Importantly, they were spared bleomycin’s toxic side effects on the lungs.
The results show how PET scans can provide unique and essential information for treating clinicians to provide ‘precision’ medicine for patients
Research consistently confirms that treating advanced-stage Hodgkin’s lymphoma – a cancer of the lymph nodes – with chemotherapy drugs has produced high survival rates.
For example, evidence from randomised trials confirm that multidrug therapy using a combination of doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) typically yields cure rates of 70 to 80 per cent, similar to rates achieved with more complex multidrug therapies.
One exception to this conclusion is the impact of an escalated multidrug treatment using bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP), with higher-than-standard doses of etoposide, doxorubicin, and cyclophosphamide.
This escalated drug regimen has been shown to yield higher progression-free survival rates than ABVD in previously untreated patients. But the benefit comes with significantly more short-term and long-term toxic effects.
Escalated BEACOPP confers a high probability of infertility, high rates of infection, prolonged fatigue and the risk of acute leukemia. In particular, bleomycin has potential to cause severe effects on the lungs, with the risk of scarring, even years later that can lead to serious breathing problems.
Due to these risks the authors of this new study wanted to assess the effect of modifying treatment by stopping bleomycin for patients who had a promising outlook and escalating treatment only for those at highest risk of the treatment not working.
The researchers used positron emission tomography (PET) to scan more than 1200 patients with advanced Hodgkin lymphoma after they received two cycles of standard ABVD chemotherapy.
Those showing no active disease according to PET scan results were randomised into two groups – one group continued with ABVD chemotherapy (including bleomycin) while the other had (AVD) chemotherapy without bleomycin.
Patients who stopped receiving bleomycin (AVD) had the same 3-year disease progression survival rates as those who continued it (ABVD) but importantly, they were spared toxic side effects on the lungs.
Those who did not have a clear PET scan after two rounds of chemotherapy, suggesting they had a more resistant lymphoma, were given more intense chemotherapy treatment with either escalated therapy containing bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP), with higher-than-standard doses of etoposide, doxorubicin, and cyclophosphamide, or BEACOPP-14 (accelerated therapy with growth hormone support).
We can tailor patients’ individual treatment and spare most of them from lung toxicity as well as the serious side effects.
What results mean for patient care
“This study showed we can tailor patients’ individual treatment and spare most of them from lung toxicity as well as the serious side effects and infertility consequences of intensive chemotherapy,” said the University of Sydney’s Associate Professor Judith Trotman, a study co-author. “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.”
Associate Professor Trotman is also Director of the Haematology Clinical Research Unit at Concord Repatriation General Hospital, and the ALLG lead investigator for the study in Australia and New Zealand.
“The results show how PET scans can provide unique and essential information for treating clinicians to provide ‘precision’ medicine for patients,” said study co-author, Dr Michael Fulham, a clinical professor at the University of Sydney and Royal Prince Alfred Hospital. “The trial conducted in seven countries is a great example of international collaboration to improve individual patient care.”
Study leader Professor Peter Johnson from Cancer Research UK and the University of Southampton, said: “Most people who get Hodgkin’s lymphoma can be cured. In this trial more than 95 per cent are alive after three years, but we still worry about the long-term side effects of the treatments we use.
“We’re now personalising treatment based on how well it works. This is a major development for patients with Hodgkin lymphoma, setting a new standard of care”.
In a NEJM editorial accompanying the new research, Professor Nancy Bartlett from Washington University School of Medicine, St Louis said: “The elimination of bleomycin after two cycles of ABVD in patients with a negative restaging PET scan does not compromise patient outcomes and results in a modest decrease in toxic effects.
“On the basis of multiple reports showing increased toxic effects of ABVD in older patients, bleomycin can and should be eliminated in all patients older than 40 years of age who have negative PET findings after two cycles of ABVD.
“Whether or not this should now be considered the standard of care in all patients is less clear in light of the low incidence of serious toxic effects in both groups.”