Patient outcomes from an international cooperative clinical trial for advanced stage Hodgkin lymphoma show “the best results we have ever seen in young patients from 18 to 60 years”, according to the trial’s Australian lead researcher, Australasian Leukaemia and Lymphoma (ALLG) Member Professor Mark Hertzberg AM.
Advanced-stage Hodgkin Lymphoma, or Hodgkin Disease (HD), often shortens life expectancy and involves very intensive toxic therapies that can incur major side-effects. The ALLG HD10 trial was part of the global German Hodgkin Study Group (GHSG) HD21 clinical trial that identified effective first-line treatments for the disease and prevented toxic side effects but maintained the effect in eliminating cancer cells.
With superior survival results, minimal side-effects and no known impact on fertility, the trial demonstrates that individualised treatment with PET2-guided BrECADD is the most effective therapy currently available for Advanced-stage Hodgkin Lymphoma and sets a new benchmark for the primary cure rate in this disease.
Professor Mark Hertzberg AM, haematologist from the Prince of Wales Hospital (NSW) and long-time ALLG clinical trial leader, is the Chief Investigator of the Australian and New Zealand arm (ALLG HD10) of this international trial established by the German Hodgkin Study Group.
“The analysis of this study, at just under three and a half years, confirmed that 95 percent of patients remain free of disease recurrence,” Prof Hertzberg said. The trial’s superior outcomes for patients will change how the disease is treated world-wide.
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The trial compared a standard intensive treatment regimen called BEACOPP-escalated with a novel modification of that regimen called BrECADD. This effectively attacked the cancer cells yet minimised both the short and long-term toxicities of the standard intensive “BEACOPP” chemotherapy regimen. Furthermore, a majority of patients completed all their planned therapy within a relatively brief 12-week period, essentially half the time of the other standard regimen used to treat this disease.
BrECADD regimen includes a novel targeted therapy called Brentuximab vedotin [a non-chemotherapy treatment], plus modifications of the standard treatment BEACOPP backbone to make it less toxic. Brentuximab vedotin contains an antibody that binds to a protein found on some lymphoma cells and causes cancer cells to die [apoptosis].
Prof Hertzberg explained “For the 60 percent or so of patients whose PET scan after only two cycles of BrECADD therapy showed a complete response, their likelihood of remaining free of disease rose to 98 percent meaning that only 2 percent of these patients showed recurrent or refractory disease within the first three years,” Prof Hertzberg explained. “Indeed, this is likely to translate into very few relapses over time.”
“The BrECADD regimen also overcomes the concerns around side effects and toxicity of BEACOPP by demonstrating that fewer patients require red blood and platelet transfusions, and, most importantly that it appears to have no adverse effect on fertility. The excellent risk-benefit ratio observed for this new treatment regimen defines a new standard of care in Germany, which will hopefully be adopted elsewhere in the world including Australia.”
Source: ALLG
About the clinical trial:
The GHSG HD21 / ALLG HD10 trial was an open-label, prospective, multicenter trial with two parallel groups and central stratified randomisation (minimisation method). The German Hodgkin Study Group (GHSG) is the premier European research agency focused on Hodgkin lymphoma, or Hodgkin disease (HD), research.
Professor Mark Hertzberg AM, haematologist from the Prince of Wales Hospital (NSW) and long-time ALLG clinical trial leader, is the Chief Investigator of the Australian and New Zealand arm (ALLG HD10) of this international trial established by the GHSG.
Patients were randomised to receive chemotherapy with escalated BEACOPP (standard group) or with BrECADD (experimental group). After the first two cycles, a restaging was performed by contrast-enhanced computed tomography (ceCT) and positron-emission tomography (FDG PET/CT) in all patients in order to guide response-adapted continuation of therapy consisting of 4 or only 2 additional cycles of randomized chemotherapy in case of a PET positive or negative staging result, respectively. A second restaging was performed after completion of chemotherapy; Patients with PET-positive residual disease received local irradiation, while patients in complete remission did not receive radiotherapy.
Co-chairman of the GHSG HD21 study, Professor Peter Borchmann of the University of Cologne presented the analysis of this international trial at the recent International Conference on Malignant Lymphoma. Results clearly demonstrate that this is now a better way of treating aggressive Hodgkin lymphoma. He highlighted ALLG’s important role in the study.
The trial was among 1,500 patients worldwide, including patients from Australia and New Zealand through the ALLG HD10. The ALLG recruited the third highest number of patients, 110 to this major international clinical trial study that involved nine countries. The Leukaemia Foundation of Australia, through the Trials
Enabling Program, provided some funding to the ALLG, assisting the opening of 16 trial sites across Australia.
Patient recruitment to the trial in Australia began in February 2018 and closed in 2020. ALLG had clinical trial sites across Australia and New Zealand (in Auckland), including in every state and capital city in Australia, as well as several large regional centres across NSW, Qld and Victoria.
The ALLG, established 50 years ago, includes over 1,000 members of blood cancer experts today and 10 international trial collaborations that enable Australian and New Zealand patients access to new treatments that are already available overseas. The ALLG HD10 trial was important for patients such as Royal New Zealand Air Force pilot Hemi Frires who joined the HD10 trial when diagnosed with Advanced stage 4B Hodgkin Lymphoma in 2018; aged only in his late 20s.
He explained “They were vague symptoms at first, fatigue and malaise, so easy to brush off and ignore but then the intense itchiness on my feet and elbows got so bad I scratched until I bled. Blood tests showed inflammation was up in my body. I then noticed inflamed lymph nodes under my collar bone. A biopsy was done. It came back as cancer.”
For Hemi specifically, the ALLG HD10 trial provided him with the option of receiving new treatments under the safety of the clinical trial setting where close monitoring and close attention to care is given.
“It seemed like a better choice for me, as it could be more effective, with a better regimen of chemo, and would be quicker,” he said. “I started the trial in 2019. It lasted three months instead of the standard six months of treatment, with chemo every two weeks.
“Fortunately, it was successful. I feel really lucky to have had a good outcome. I was able to get back to living life normally, back to work with a full head of hair. I am back to fighting fit, and back to flying in the Air Force.”
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