vom 12.12.2022

Acute Myeloid Leukemia: Germany-wide clinical trial challenges international standard of care

Joint press release of the National Center for Tumor Diseases Dresden (NCT/UCC) and DKMS

Dresden/Tuebingen, Germany, December 11, 2022. Prior to allogeneic stem cell transplantation for the treatment of acute myeloid leukemia (AML), complete remission is currently still considered the gold standard of care. A Germany-wide clinical trial now shows for the first time that this approach does not benefit disease-free survival or overall survival. An alternative approach of sequential conditioning followed by immediate stem cell transplantation may reduce side effects and shorten hospital stays. This important conclusion was reached in the trial led by researchers at the University Hospital Carl Gustav Carus Dresden and at the National Center for Tumor Diseases Dresden (NCT/UCC). The trial was facilitated and organized by DKMS as pharmaceutical sponsor and supported by the Study Alliance Leukemia (SAL) and the Cooperative German Transplant Study Group. Prof. Johannes Schetelig, Head of the Stem Cell Transplantation Unit at the University Hospital Dresden and Head of the DKMS Clinical Trials Unit, presented the findings from this trial on December 11 at the world's largest hematology congress - the 64th American Society of Hematology (ASH) Annual Meeting and Exposition - in New Orleans, Louisiana.

Until now, patients with acute myeloid leukemia have been treated with high-dose chemotherapy in an attempt to reduce the disease to the point where no leukemia cells are detectable (complete remission) prior to transplantation of non-patient (allogeneic) blood stem cells. In a large-scale Germany-wide trial, which was largely funded by the international non-profit organization DKMS, a team of researchers has now been able to show that the previously targeted complete remission does not bring any significant advantage for overall survival and disease-free survival. Rather, the trial suggests that if an HLA-compatible donor is available, 12 days of preparatory chemotherapy followed by immediate transplantation yields comparable treatment outcomes with fewer side effects and shorter hospital stays.
"The results of our trial challenge an international standard of leukemia therapy and were also surprising for us," emphasizes the trial’s Lead Prof. Johannes Schetelig. "They suggest that if a HLA-compatible stem cell donor is available, transplantation should be performed as soon as possible, even if leukemia cells are still detectable in the patient's body. Immediate transplantation without previously seeking complete remission can reduce overall side effects and shorten hospital stays."

"Allogeneic stem cell transplantation is the most effective treatment option for patients with refractory or relapsed AML. The previous goal of complete remission is only achievable in approximately 50 percent of patients, even with intensive chemotherapy. If the corresponding treatment is not successful, patients in Germany often receive further therapies with similarly unsatisfactory chances of success. Alternatively, the goal of complete remission can be disregarded and, after appropriate pre-treatment, stem cell transplantation can be offered directly," says Lead Author Prof. Matthias Stelljes, Head of the Bone Marrow Transplantation Unit at Münster University Hospital. "In other countries with less comprehensive healthcare, stem cell transplantation is often not performed after failed complete remission, also for cost reasons. Eliminating this cost-intensive intermediate step could thus open up the possibility of stem cell transplantation to more AML patients worldwide, which in many cases is the only chance of a cure."

Within the clinical trial, the intention-to-treat population included 276 adult AML patients who were scheduled to receive an allogeneic stem cell transplant due to a poor response to initial chemotherapy or relapse. In all patients, a donor had already been found or the donor search was well advanced. The trial participants were randomized into two groups of approximately equal size. In group 1, an attempt was made to achieve complete remission in preparation for transplantation. Patients in group 2 underwent 12 days of preparatory therapy followed by immediate transplantation if a donor was available. In the first group, complete remission was achieved in 46 percent of the patients. In 5 percent of those affected, a second attempt was made to achieve complete remission by means of high-dose chemotherapy; the remaining patients received preparatory therapy and stem cell transplantation without this further attempt. In group 1, the median time to transplant initiation was eight weeks. In the second group, transplantation was performed after a median of four weeks.

Leukemia-free survival one year after transplantation showed no significant differences between the two groups (69% vs. 71.5%),nor did overall survival one year and three years after trial inclusion (71.9% vs. 69.1% and 54.2% vs. 51%, respectively).

"The perspective shown for AML therapy of reducing side effects and hospitalizations while maintaining good treatment outcomes is groundbreaking," says Prof. Michael Albrecht, Medical Director of the University Hospital Carl Gustav Carus. "The current trial is an impressive example of the fact that Dresden's cancer research is now generating impetus from which patients worldwide are benefiting. Just 25 years ago, hardly anyone would have thought this possible!"

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

Contact for the press:
Dr. Anna Kraft
National Center for Tumor Diseases Dresden (NCT/UCC)
Press and Public Relations
Phone: +49 (0)351 458-5548
E-mail: anna.kraft@nct-dresden.de

Dr. Laura Schulz
Global Corporate Communications
Phone: +49 (0)221 940582-3243
E-mail: lschulz@dkms.de

Nina Louis
Phone: +49 221 94 05 82-3333
E-mail: louis@dkms.de

Dr. Sibylle Kohlstädt
German Cancer Research Center (DKFZ)
Strategic Communications and Public Relations
Phone: +49 (0)6221 42-2854
Fax: +49 (0)6221 42-2968
E-mail: s.kohlstaedt@dkfz.de

Stephan Wiegand
Public Relations & Marketing
Carl Gustav Carus Medical Faculty of the Dresden University of Technology
Phone: +49 (0) 351 458-19389
Fax: +49 (0) 351 458-885486
E-mail: stephan.wiegand@tu-dresden.de

Holger Ostermeyer
University Hospital Carl Gustav Carus Dresden Press Office
Phone: +49 (0)351 458-4162
Fax: +49 (0)351 449210505
E-mail: Pressestelle@uniklinikum-dresden.de www.uniklinikum-dresden.de

Simon Schmitt
Communication and Media | Management and Press Spokesman
Helmholtz Center Dresden-Rossendorf
E-mail: s.schmitt@hzdr.de
Phone: +49 351 260-3400

National Center for Tumor Diseases Dresden (NCT/UCC)
The National Center for Tumor Diseases Dresden (NCT/UCC) is a joint institution of the German Cancer Research Center, the Carl Gustav Carus Faculty of Medicine at TU Dresden, the Carl Gustav Carus University Hospital Dresden and the Helmholtz-Zentrum Dresden-Rossendorf (HZDR).
The NCT has made it its duty to closely link research and patient care wherever possible. That is why cancer patients at the NCT sites can be treated based on the latest research results. At the same time, the proximity of laboratory and clinic provides researchers with important impulses for their practice-oriented research. The NCT sites share the common goal of developing the NCT into a top international center for patient-oriented cancer research. The Dresden center draws on the structures of the University Cancer Center Dresden (UCC), which was founded in 2003 as one of the first Comprehensive Cancer Centers (CCC) in Germany. Since 2007, the UCC has been honored by the German Cancer Aid e.V. (DKH) as a "Top Oncological Center" on a continuous basis.

About DKMS
DKMS is an international non-profit organization dedicated to saving the lives of patients with blood cancer. Founded in Germany in 1991 by Dr. Peter Harf, DKMS and the organization’s 1,000 employees have since relentlessly pursued the aim of giving as many patients as possible a second chance at life. With over 11,5 million registered donors, DKMS has succeeded in doing this more than 100,000 times to date by providing blood stem cell donations to those in need. This accomplishment has led to DKMS becoming the global leader in the facilitation of unrelated blood stem cell transplants. The organization has offices in Germany, the US, Poland, the UK, Chile and South Africa. In India, DKMS has founded the joint venture DKMS-BMST together with the Bangalore Medical Services Trust. International expansion and collaboration are key to helping patients worldwide because, like the organization itself, blood cancer knows no borders.
DKMS is also heavily involved in the fields of medicine and science, with its own research unit focused on continually improving the survival and recovery rate of patients. In its high-performance laboratory, the DKMS Life Science Lab, the organization sets worldwide standards in the typing of potential blood stem cell donors.

German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ)
The German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) with its more than 3,000 employees is the largest biomedical research institution in Germany. More than 1,300 scientists at the DKFZ investigate how cancer develops, identify cancer risk factors and search for new strategies to prevent people from developing cancer. They are developing new methods to diagnose tumors more precisely and treat cancer patients more successfully. The DKFZ's Cancer Information Service (KID) provides patients, interested citizens and experts with individual answers to all questions on cancer.
Jointly with partners from the university hospitals, the DKFZ operates the National Center for Tumor Diseases (NCT) in Heidelberg and Dresden, and the Hopp Children's Cancer Center KiTZ in Heidelberg. In the German Consortium for Translational Cancer Research (DKTK), one of the six German Centers for Health Research, the DKFZ maintains translational centers at seven university partner locations. NCT and DKTK sites combine excellent university medicine with the high-profile research of the DKFZ. They contribute to the endeavor of transferring promising approaches from cancer research to the clinic and thus improving the chances of cancer patients.
The DKFZ is 90 percent financed by the Federal Ministry of Education and Research and 10 percent by the state of Baden-Württemberg. The DKFZ is a member of the Helmholtz Association of German Research Centers.

University Hospital Carl Gustav Carus Dresden
The University Hospital Carl Gustav Carus Dresden offers medical care at the highest level of care. As a full-service hospital, it covers the entire spectrum of modern medicine. The University Hospital combines 20 clinics and outpatient departments, four institutes and ten interdisciplinary centers that collaborate closely with the clinical and theoretical institutes of the Faculty of Medicine.
With 1,295 beds and 160 places for day-care treatment, the Dresden University Hospital is the largest hospital in the city and also the only full-service hospital in eastern Saxony. Around 860 doctors cover the entire spectrum of modern medicine. 1,860 nurses and caregivers ensure the patients' well-being. The medical care of patients suffering from cancer, metabolic and neurodegenerative diseases is an important focus of treatment at the University Hospital.
Germany's largest hospital comparison by the news magazine "Focus" confirms that the University Hospital Carl Gustav Carus Dresden provides an excellent quality of treatment. That is why Dresden's university medicine comes second in the Germany-wide ranking.

Carl Gustav Carus Faculty of Medicine at Technische Universität Dresden
The Dresden University Medicine, consisting of the Carl Gustav Carus Faculty of Medicine and the university hospital of the same name, has specialized in research in the fields of oncology, metabolic as well as neurological and psychiatric diseases. Within these focal areas, the topics of degeneration and regeneration, imaging and technology development, immunology and inflammation, as well as prevention and health care research are of particular interest. International exchange is a prerequisite for top-level research - the Dresden University Medical Center embraces this concept with employees from 73 nations and numerous collaborations with researchers and teams from all over the world.

Helmholtz-Zentrum Dresden-Rossendorf (HZDR)
The Helmholtz-Zentrum Dresden-Rossendorf (HZDR) conducts research in the fields of energy, health and matter. It focuses on the following questions:
•    How can energy and resources be used in an efficient, safe and sustainable way?
•    How can cancer be better visualized, characterized and effectively treated?
•    How do matter and materials react under the influence of strong fields and in smallest dimensions?
To answer these scientific questions, the HZDR operates large infrastructures that are also used by external measurement guests: Ion Beam Center, High Field Magnetic Laboratory Dresden and ELBE Center for High Power Radiation Sources.
The HZDR is a member of the Helmholtz Association, has five sites (Dresden, Freiberg, Grenoble, Leipzig, Schenefeld near Hamburg) and employs almost 1,200 people - about 500 of whom are researchers including 170 PhD students.