New enzyme inhibitor improves AML treatment

Acute myeloid leukaemia: study proves efficacy of tyrosine kinase-inhibiting drug for the first time

A comparative study involving 25 German hospitals, including Universitätsklinikum Erlangen, has proven the efficacy of the enzyme inhibitor Sorafenib in younger patients with acute myeloid leukaemia (AML) for the first time. A total of 267 patients who were treated at 25 hospitals took part in the research project. In addition to standard chemotherapy, half of the participants were given tablets containing Sorafenib while the other half were given a placebo. At the end of the three-year observation period the results were clear. The survival rate without a recurrence of AML was more than 18 percent higher for the group who took Sorafenib when compared with the control group.

Enzyme inhibitors open up new cancer treatment possibilities

Enzyme inhibitors take advantage of the weaknesses of tumour cells which are less differentiated and therefore less mature than the human body’s normal cells. They also divide more quickly. In recent years, researchers have developed pharmaceutical agents on the basis of this knowledge which inhibit certain enzymes that are responsible for the reproduction of cancer cells, thereby slowing down or stopping tumour growth. One of these active agents – Sorafenib – inhibits a group of enzymes known as tyrosine kinases. It is already used to treat malignant tumours in the liver, kidneys and thyroid. Tyrosine kinase inhibitors (TKI) are usually used in addition to conventional chemotherapy which aims to destroy cancer cells. As the drugs used in chemotherapy, known as cytostatic drugs, generally do not reach all of the cells, enzyme inhibitors are an important form of additional treatment in order to slow down or even stop tumour regrowth.

Development of these specific inhibitors improves life expectancy for certain types of leukaemia significantly

Although the effectiveness of TKI in the treatment of chronic myeloid leukaemia and acute lymphatic leukaemia has already been proven, its significance in the treatment of acute myeloid leukaemia was previously unclear. Findings related to various mutations which cause the disease prompted researchers to investigate the efficacy of Sorafenib against this type of leukaemia. Sorafenib inhibits several enzymes that stimulate the growth of leukaemia cells. To examine the safety and efficacy of Sorafenib, the University Hospital Dresden set up a study as part of its project Studienallianz Leukämie, a study platform for research into AML treatment. Doctors from 25 German hospitals took part and recruited 267 AML patients aged between 18 and 60. FAU’s Chair of Haematology/Internal Oncology, led by Prof. Dr. Andreas Mackensen, played a significant role.

In addition to conventional treatment, 134 participants were given Sorafenib and 133 were given a placebo. After a three-year observation period, the patients who had received the additional Sorafenib treatment had a medium-term event-free survival rate of 20.5 months and a relapse-free survival rate of 56 percent. By comparison, a medium-term event-free survival rate of 9.2 months and a relapse-free survival rate of 38 percent was recorded for the group of patients who received standard therapy plus the placebo. ‘In general the combined treatment was well tolerated by patients, although those who received Sorafenib had slightly higher rates of fever and redness of skin,’ says PD Dr. Christoph Röllig.

Further genetic analyses will now be carried out in order to clarify which patients benefited particularly from the Sorafenib treatment.

The doctors and researchers presented their findings on 8 December at the 56th Annual Meeting of the American Society of Hematology in San Francisco. The significance of the research results was also reflected in the fact that the presentation given by the project co-ordinator, PD Dr. Christoph Röllig from the University Hospital Dresden, was voted best clinical trial among 4000 contributions to the event. The American Society of Hematology’s Annual Meeting is the most important event of the year in the field of leukaemia research.

Participating hospitals

Westpfalz-Klinikum Kaiserslautern, Städtisches Klinikum Nord Nürnberg, St. Marien-Hospital Hamm, Universitätsklinikum Münster, Robert-Bosch-Krankenhaus Stuttgart, Universitätsklinikum Erlangen, Klinikum Bamberg, Klinikum Chemnitz, Universitätsklinikum Heidelberg, Diakonie-Krankenhaus Schwäbisch Hall, Universitätsklinikum Würzburg, Universitätsklinikum Dresden, HSK Wiesbaden, St. Bernward Krankenhaus Hildesheim, Klinikum der Universität Regensburg, Universitätsklinikum Marburg, Diakonie-Krankenhaus Bremen, Klinikum Bayreuth, Charite Campus CBF Berlin, Städtische Kliniken Bielefeld, St. Johannes Hospital Duisburg, Diakoniekrankenhaus Rotenburg (Wümme), Universitätsklinikum Essen, Universitätsklinikum Frankfurt am Main, Universitätsklinikum Rostock

Further information:

Prof. Dr. Andreas Mackensen
+49 9131 8535954 (secretary’s office)
med5-direktion@uk-erlangen.de