Melbourne researchers have identified a gene mutation in the leukaemia cells of patients who become resistant to venetoclax, a discovery which can be used to identify those at-risk of relapse and help improve outcomes from this breakthrough blood cancer drug.
Venetoclax was developed based on discoveries made in Melbourne at the Walter and Eliza Hall Institute (WEHI) around 30 years ago. The BCL2 inhibitor can induce long-term remissions in many patients with Chronic Lymphocytic Leukaemia (CLL) where other standard treatments are not effective.
Early support by ACRF to WEHI for the development of Venetoclax has been key to the drug’s development. ACRF has provided three grants, totalling AUD 5.5 million towards cutting edge cancer research equipment and technology.
However in some patients on venetoclax for CLL their disease will progress and, until now, factors leading to this have remained unknown. The study – involving Peter Mac’s Dr Piers Blombery and collaborators at the Walter and Eliza Hall Institute, Royal Melbourne Hospital and University of Melbourne – found a specific genetic mutation developing in the leukaemia cells of seven patients who relapsed while taking venetoclax.
Dr Blombery presented the results of this research in the prestigious “Late Breaking” session at the American Society of Haematology (ASH) annual scientific meeting, in San Diego, overnight. “We conducted a genomic assessment of cancer cells from relapsing disease in patients and found a very specific single mutation in BCL2, the target of venetoclax, which significantly reduces the drug’s efficacy against the leukaemia in these patients,” Dr Blombery says.
“Importantly, this mutation could be detected in the bone marrow in some cases years before a patient’s disease would clinically progress, so this opens the door for testing to identify those at-risk so we can potentially intervene before overt relapse occurs.”
Dr Blombery said the study also pointed to other, as yet undiscovered, drivers of venetoclax resistance in patients and the genomics work would continue. Professor Andrew Roberts, from the Walter and Eliza Hall Institute, said the research was only possible because of long-standing collaborations and fantastic teamwork between clinicians and laboratory scientists from many disciplines.
“Venetoclax remains a very effective treatment for CLL. This key clue should help us develop combination treatments with venetoclax that are even better for people with CLL,” Prof Roberts also says.
Supporters of this research include the Snowdome Foundation – which has a mission to accelerate new therapies for Australian blood cancer (myeloma, lymphoma and leukaemia) patients to help them live longer, better lives – and the Christine and Bruce Wilson Centre for Lymphoma Genomics based at Peter Mac; Vision Super, the Leukemia and Lymphoma Society (USA), the Leukaemia Foundation, NHMRC, Australian Cancer Research Foundation and Cancer Council Victoria.
This article and image originally appeared on the Peter MacCallum Cancer Centre website.