First DKMS clinical trial has practice changing results for patients with acute myeloid leukemia (AML)
In acute myeloid leukaemia (AML), the standard of care is to attempt complete remission before stem cell transplantation. Complete remission means that the disease is no longer detectable by available diagnostic measures.
This imperative is now being challenged by the results of the first-ever completed clinical trial facilitated and organised by DKMS. The results of this trial suggest that adult patients dealing with relapse or refractory AML should receive stem cell transplantation as soon as possible. Contrary to earlier assumptions, achieving complete remission prior to transplantation does not increase the overall chances for life but even unnecessarily prolongs chemotherapy, associated side effects, and hospitalisation.
This important conclusion was reached by the researchers at the University Hospital Carl Gustav Carus Dresden and at the National Center for Tumor Diseases Dresden (NCT/UCC). Professor Dr. Schetelig, Head of the Department of Stem Cell Transplantation at the University Hospital Dresden (Germany) and Head of the DKMS Clinical Trials Unit, presented the results on December 11 at the world's largest haematology congress, the annual meeting of the American Society of Hematology (ASH) in New Orleans, USA. The study was supported by the Study Alliance Leukemia (SAL), the Cooperative German Transplant Study Group and Münster University Hospital.
Adult patients with poorly responding, non-favourable AML after initial induction therapy or those who have already relapsed are usually advised to undergo allogeneic stem cell transplantation, as a chance for long-term cure. An important step prior to this life-saving therapy has always been to bring the patient back into complete remission by high-dose chemotherapy.
The goal of the randomised controlled trial led by Professor Schetelig was to get patients to transplantation as soon as possible. This coined the name of this trial: ASAP.
The team of researchers collected data from 281 patients with a median age of 61 years who were divided into two groups. According to standard practice, group one was treated with prolonged chemotherapy before stem cell transplantation to achieve complete remission. Group two received a transplant after only a short 12-day conditioning period without the intention of achieving complete remission prior to transplantation. A prerequisite for stem cell transplantation was, of course, the availability of a matched allogeneic donor.
The common practice of achieving complete remission before transplantation shows no advantage in terms of overall success or overall survival. Moreover, patients in the alternative study arm not only achieved the same outcome - they also benefited from fewer side effects by not having to undergo lengthy high-dose chemotherapy and their median hospital stay was only half as long. “The results of our clinical trial challenge the international standard of leukaemia therapy and were also surprising for us. They suggest that if an HLA-compatible stem cell donor is available, transplantation should take place as soon as possible, even if leukaemia cells are still detectable in the patient's body,” says Professor Schetelig. “Moreover, these results underscore the need for early initiation of donor search, possibly at the time of diagnosis but at the latest after receipt of genetic reports which show a non-favourable risk profile for AML.”
Even with intensive chemotherapy, the previously targeted complete remission can only be achieved in about 50 percent of patients. If the corresponding treatment is unsuccessful, most patients have so far received a second intensive chemotherapy with correspondingly burdensome side effects, depending on their overall state of health.
Immediate transplantation without a prior attempt at complete remission could not only reduce side effects and shorten hospital stays, but also allow more patients access to this potentially life-saving therapy. “This is especially true for countries with less comprehensive healthcare, where stem cell transplantation is often not performed after a failed complete remission, also for cost reasons. Eliminating this expensive intermediate step could therefore open up the possibility of stem cell transplantation to more AML patients worldwide, which in many cases is the only chance of a cure," explains Professor Schetelig.
"Normally, sponsors of clinical research pursue economic interests. It is unusual to conduct a clinical trial that questions the use of a standard medical intervention; usually, it is the other way around. That’s why it’s necessary for nonprofit organisations like DKMS to also conduct clinical research. This way, we can ensure that patients receive the best possible treatment and that we actually advance patient care," said Dr. Alexander Schmidt, Global Chief Medical Officer at DKMS.
M. Stelljes et. al.: In Patients with Relapsed/Refractory AML Sequential Conditioning and Immediate Allogeneic Stem Cell Transplantation (allo-HCT) Results in Similar Overall and Leukemia-Free Survival Compared to Intensive Remission Induction Chemotherapy Followed By Allo-HCT: Results from the Randomized Phase III ASAP Trial. Blood (2022) 140 (Supplement 1): 9-11. https://doi.org/10.1182/blood-2022-159962.