Alongside his colleague Dr. Leo Ruhnke (right side), Prof. Christoph Röllig (left side) designed and supervised the RELAX study
Photo Credit: Courtesy of Dresden University
Scientific Frontline: "At a Glance" Summary: Acute Myeloid Leukemia Combination Therapy
- Main Discovery: The addition of the BCL2 inhibitor venetoclax to intensive chemotherapy substantially improves treatment outcomes for patients suffering from relapsed or refractory acute myeloid leukemia.
- Methodology: Researchers conducted a multicenter phase 1/2 clinical trial known as the RELAX study to evaluate the tolerability and efficacy of combining a standard chemotherapy regimen of cytarabine and mitoxantrone with venetoclax.
- Key Data: The experimental combination therapy achieved a 75 percent complete remission rate, representing a stark increase over the 40 percent remission rate historically observed with conventional chemotherapy alone.
- Significance: By effectively suppressing rapidly growing leukemia cells, this therapeutic approach successfully qualifies a significantly larger proportion of treatment-resistant patients for potentially curative stem cell transplantations.
- Future Application: The treatment regimen is currently undergoing expanded evaluation in over 150 additional patients and demonstrates strong potential to become the new standard of care for treating acute myeloid leukemia relapses.
- Branch of Science: Hematology, Oncology, and Clinical Pharmacology.
- Additional Detail: The therapeutic combination maintained high efficacy even against particularly resistant genetic variants of the disease, with the foundational findings formally published in The Lancet Haematology.
Acute myeloid leukemia (AML) is a particularly aggressive form of blood cancer that usually progresses rapidly if swift and intensive treatment is not applied. Although the disease can often be contained by chemotherapy (remission), it returns in many patients. A permanent cure is often only possible with a stem cell transplant - provided that the leukemia can be sufficiently contained beforehand. A new Germany-wide study led by the Dresden University Medicine has shown that the combination of intensive chemotherapy and the substance venetoclax can significantly improve the success rate of treatment of aggressive acute leukemia. This has been confirmed by the results of RELAX, with remission in 75% of the cases compared to the past attempts yielding an only 40 percent remission rate. The study was published today, March 4, in the renowned journal The Lancet Hematology.
"If AML stops responding to conventional intensive chemotherapy or comes back, the chances of a long-term cure decrease significantly," explains Prof. Christoph Röllig, Head of Hematology and Clinical Trials at Medical Clinic 1 of the University Hospital Dresden and the Faculty of Medicine at TUD Dresden University of Technology. In this case, we aim to provide patients with a potentially curative stem cell transplant. "By this time, however, it can be difficult to catch the fast-growing AML with chemotherapy." With conventional treatments, only around 40 percent of those affected manage to suppress acute myeloid leukemia to such an extent that a so-called complete remission is achieved, i.e., the disease is below the detection limit and the blood count recovers.
Alongside his colleague Dr. Leo Ruhnke, Christoph Röllig designed and supervised the RELAX study – an early phase 1/2 study. The researchers investigated whether the combination of standard therapy with cytarabine and mitoxantrone (HAM) alongside the so-called BCL2 inhibitor venetoclax can improve the success rate of such therapy. As a first step, Röllig and Ruhnke's research team tested the tolerability in the RELAX study; in a second step, they tested the efficacy of the HAM and venetoclax ("HAM-Ven") combination.
"With the novel HAM-Ven combination, we increased the remission rates previously observed with conventional chemotherapy from 40 percent of patients with relapsed AML to 75 percent. The majority of those treated were able to successfully receive a stem cell transplant," reports Leo Ruhnke, senior hematologist and first author of the publication. The therapy also works well for particularly persistent, genetic forms of AML.
"The current results indicate an encouragingly good prognosis for the patients treated in the study," says Prof. Martin Bornhäuser, Director at Medical Clinic I, member of the Directorate of the National Center for Tumor Diseases (NCT/UCC) Dresden and Professor at TU Dresden. "The RELAX study shows how academic, clinical research in cooperation with industrial partners can significantly improve the treatment of cancer."
"The innovative treatment approach is already reaching those affected," says Christoph Röllig. “Together with colleagues from Munster we are currently analyzing the results of more than 150 additional AML patients who were treated in Germany with the HAM-Ven regimen after the end of the study’s recruitment period. The initial data is promising."
The new therapy developed in Dresden therefore has a strong chance of establishing itself as a new standard of care for relapsed AML and as a bridge to a life-saving stem cell transplant, thereby improving patients’ chances of recovery.
"The RELAX study illustrates how scientific excellence and clinical expertise go hand in hand in Dresden to develop innovative therapies," explains Prof. Esther Troost, Dean of the Faculty of Medicine at TUD: "It is only through these kinds of studies that we can ensure the safety and efficacy of new treatment approaches."
"The results of the RELAX study mark a significant leap forward, as they provide us with new and effective options to better prepare patients for a life-saving stem cell transplantation," says Prof. Uwe Platzbecker, Medical Director of Dresden University Hospital.
About the study: The study project was designed under the sponsorship of the Faculty of Medicine at TU Dresden and in cooperation with Dresden’s Coordination Center for Clinical Studies by the Clinical Studies Department of the Medical Clinic and Polyclinic I at Dresden University Medicine and implemented at various centers in Germany as part of the Study Alliance Leukemia (SAL) academic study group. With over 50 participating centers in Germany and Austria, SAL is one of the two large German AML study groups and is coordinated by its Dresden-based study center. . Partners included the hematology departments of the university hospitals in Münster, Kiel, Essen, Frankfurt am Main, Würzburg, Augsburg, Marburg, Nuremberg, the Robert Bosch Clinic in Stuttgart, the Chemnitz Clinic and the Red Cross Clinic in Munich.
Funding: The company AbbVie supported the project financially and provided the medication used in the study
Published in journal: The Lancet Haematology
Authors: Leo Ruhnke, MD, Prof Christoph Schliemann, MD, Jan-Henrik Mikesch, MD, Prof Matthias Stelljes, MD, Lars Fransecky, MD, Björn Steffen, MD, Martin Kaufmann, MD, Prof Andreas Burchert, MD, Prof Andreas Rank, MD, Maher Hanoun, MD, Alexander Höllein, MD, Sabrina Kraus, MD, Kerstin Schäfer-Eckart, MD, Prof Mathias Hänel, MD, Annett Haake, RN, Frank Fiebig, MS, Michael Kramer, MS, Sven Zukunft, MS, Désirée Kunadt, MD, Jan Moritz Middeke, MD, Katja Sockel, MD, Prof Johannes Schetelig, MD, Prof Uwe Platzbecker, MD, Prof Malte von Bonin, MD, Maximilian Alexander Röhnert, MD, Uta Oelschlägel, PhD, Lisa Wagenführ, PhD, Prof Christian Thiede, MD, Sylvia Herold, PhD, Prof David Poitz, PhD, Prof Friedrich Stölzel, MD, Prof Claudia Dorothea Baldus, MD, Prof Hubert Serve, MD, Prof Martin Wermke, MD, Prof Martin Bornhäuser, MD, and Prof Christoph Röllig, MD
Source/Credit: Dresden University
Reference Number: ongy030526_01
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