Improving outcomes for Philadelphia chromosome positive leukaemias-optimising outcomes through novel regimens incorporating targeted inhibitors

An abnormal protein called BCR-ABL can cause chronic myeloid leukaemia and a high-risk subtype of acute lymphoblastic leukaemia (CML & Ph+ ALL in short). This protein sends signals to enhance cell growth and prevent cell death. These signals can be stopped by blocking the protein using small molecules taken as medications called TKIs. Although many patients benefit from these drugs, some CML patients have resistance or side effects to these drugs, whilst many ALL patients will still die of their disease.

My research program will find new ways to target these leukaemias. A new drug called Asciminib will be tested for CML. Asciminib binds to a different location on the BCR-ABL protein as compared to other drugs, with potentially additive benefits. With my collaborators, I am conducting a clinical trial to use this drug, and perform experiments on understanding if certain patients will benefit most from this new therapy. Eventually, Asciminib will also be tested, in combination with other drugs, for Ph+ ALL. In the mean time, I will partner with Italian haematologists to trial a chemotherapy free treatment for Ph+ ALL, using a targeted therapy called ponatinib, together with blinatumomab, which engages the patient’s own immune to destroy leukaemia cells. I will examine the genomic events that may influence treatment outcomes, and develop ultra sensitive methods to detect any leukaemia left behind after treatment.

This research will lead to better understanding of Ph+ leukaemias and introduce more effect, less toxic therapies.