Professors John Seymour, Mark Dawson and Sarah-Jane Dawson, and Dr Piers Blombery, spoke as presenting authors at the ASH annual scientific meeting in San Diego recently. Attendees learned the latest about their discoveries and successful clinical trials at Peter Mac. These presentations were among a total of 40 papers delivered with Haematology staff as contributing authors, including 16 oral presentations.

Professor John Seymour, Director of Clinical Haematology at Peter Mac and RMH, described the response to the achievements of the Clinical Haematology team as phenomenal.

“For example, our work in Chronic Lymphocytic Leukemia is as prominent and influential as any of the major cancer centres around the world,” he said. “We are setting the direction for investigation and treatment globally.”

Prof John Seymour presented the results of the MURANO phase III clinical trial, a game-changer for patients with a particular form of blood cancer. Before joining the trial, these patients had been heavily treated with a combination of drugs for chronic lymphocytic leukemia (CLL) but their disease had relapsed. On the MURANO trial, these patients were treated with the Parkville precinct-developed BCL2-targeting drug venetoclax, in combination with another immunotherapy drug, rituximab. Three years on, many of these patients had no detectable cancer and were able to cease therapy and continue to be observed.

Professor Sarah-Jane Dawson presented on her research that asked why the disease in 30 per cent of patients with Mantle Cell Lymphoma failed to respond to the our most effective novel therapies, a combination of ibrutinib and venetoclax. Together with Professor Mark Dawson, she found that this group of patients had gene mutations that resulted in increased levels of a protein called BClxL, which protected the cancer cells from the drug therapy. Her research showed that these gene mutations could be detected through a liquid biopsy, which allows trace amounts of cancer DNA to be detected in a patient’s blood. With this information, Professor Dawson identified that the resistance to venetoclax and ibrutinib could be counteracted by the addition of an additional drug, navitoclax, which acts as a BCLxL inhibitor.  Clinical trials of this new combination therapy are expected to commence here next year.

Professor Mark Dawson reported research that has found the key principles by which cancers evolve resistance to various therapies without requiring a new genetic mutation. The process involves reprogramming of cells through the coordinated action of various proteins known as epigenetic regulators. These regulators modify the way that genes are expressed in cancer cells, which then allows them to escape the effects of therapy.  Understanding the principles of this process has highlighted potential new ways to reverse this drug resistance with existing epigenetic therapies. These insights will underpin an upcoming clinical trial that will be run by the Australasian Leukaemia and Lymphoma Group across Australia next year.

Dr Piers Blombery presented in the prestigious ‘Late Breaking’ session at the ASH meeting on his group’s work into venetoclax resistance. He had led a large multi-skilled team of precinct researchers that identified a gene mutation in the CLL cells of patients whose disease had become resistant to venetoclax. The discovery of the specific single mutation in BCL2, the target of venetoclax, renders the drug less effective and potentially leads to a subsequent relapse of CLL. Dr Blombery’s team research means that patients’ risk of relapse can be tested and treatment can potentially be tailored to prevent relapses.

Watch this short video from ASH 2018 of Professor Seymour sharing the updated results from the phase III MURANO  trial.