Drug-screening in AML at Relapse for Targeted Treatment (DARTT-1)

This is a non-randomised clinical study investigating subsequent patients with specific AML treatment started between January 1, 2022 until December 31, 2022. Patients with relapsing disease are planned to be analyzed in this study

The standard treatment for young fit patients with acute myeloid leukemia (AML) is intensive chemotherapy followed by consolidation treatment with curative intent. Usually, two cycles of intensive chemotherapy are given, with subsequent consolidation treatment depending on the genetic risk-assessment of the patients as well as on the response to the induction treatment. For elderly or unfit patients, such an intensive approach is not feasible, and palliative treatment must be considered. The standard first-line-treatment for such patients since more than a decade comprises repetitive cycles of a hypomethylating agent (either Azacitidine or Decitabine). The median progression free survival following these approaches in this population is between 4 and 8 months, with an overall-survival of up to 12 months. More recently, the addition of the Bcl-2 inhibitor Venetoclax to hypomethylating agents has led to a modest improvement both of progression-free and overall survival. However, overall survival in such patients usually does not exceed 14-16 months. The laboratory of Prof. Berend Snijder, Institute of Molecular Systems Biology, at the ETH (Eidgenössische Technische Hochschule) Zurich has developed an image-based ex-vivo drug screening platform for patients with aggressive haematological malignancies, also called pharmacoscopy. Using such a technique, leukemic cells from a patient at relapse can be rapidly screened for sensitivity to single compounds. A drug score is calculated for each compound. Starting in Q2/2021, the investigator at the Department of Medical Oncology, University Hospital Inselspital in Bern, collected experiences using such an approach. Having received information from the laboratory on top sensitivity of leukemic cells of a given patient to a specific drug, a process is initiated to try to obtain access to such off-label drugs.

Leukemic cells from a patient at relapse can be screened for sensitivity to single compounds. A drug score is calculated for each compound (defined as 1 - (% target cells in drug treated conditions / % target cells under control condition)). If a drug kills all target cells specifically, the best possible score is "1". If the drug is killing all non-target cells, the score goes to negative infinite. If a drug kills both target and non-target cell populations equally, or does nothing, the score is "0".

Percentage of patients with relapsing AML in which drug screening identifies a promising effective drug and in which such a treatment effectively is started

Number of patients responding to their chosen therapy regimen in correlation to the RBF (relative blast fraction) value

Duration of response in patients responding to their chosen therapy regimen in correlation to the RBF (relative blast fraction) value

Overall survival of patients responding to their chosen therapy regimen in correlation to the RBF (relative blast fraction) value

Inclusion Criteria: Included are patients with AML at relapse treated at the Department of Medical Oncology at the University Hospital Inselspital in Bern. Patients are not planned to undergo intensive reinduction treatment with subsequent allogeneic hematopoietic transplantation in a curative intent. Patients have exhausted all standard therapeutic options and they must have no available licensed standard treatment for relapsed AML. Written informed consent Exclusion Criteria: Patients able to undergo intensive reinduction treatment with subsequent allogeneic hematopoietic transplantation in a curative intent Patients have available standard therapeutic options