Joanne and Rachel
14 August 2019
News Category: 

A drug developed in Melbourne, approved for the treatment of Chronic Lymphocytic Leukaemia (CLL) is being repurposed by Royal Melbourne Hospital researchers to reduce harsh side effects of radiation and chemotherapy before stem cell and bone marrow transplantation. 

Venetoclax, the potent anti-cancer drug discovered by researchers at the Royal Melbourne Hospital, the Peter MacCallum Cancer Centre and the Walter and Eliza Hall Institute of Medical Research, has been shown to reduce the need for aggressive chemo- and radiation therapy prior to a bone marrow or stem cell transplant.

Dr Joanne Davis and Dr Rachel Koldej, Royal Melbourne Hospital researchers at the Victorian Comprehensive Cancer Centre, said initial testing has shown that using Venetoclax in mice with acute myeloid leukaemia (AML) before stem and bone marrow transplantation improves outcomes post-transplant.

“Traditionally, we’ve had to kill a patient’s entire immune system through aggressive chemotherapy and radiation therapy before a transplant or patients’ bodies may start to reject the transplant as their old immune system starts to attack the new one,” Dr Davis said.

“Through using Venetoclax, we’ve seen there’s a real opportunity to reduce the intensity of treatment, which will reduce some of the horrible side effects we see with the aggressive pre-transplant regime in patients with AML, and be able to successfully complete a transplant.”

Stem and bone marrow transplantation is a preventative measure for AML patients in order to reduce risk of relapse. Side effects from aggressive chemo- and radiation therapy prior to transplant can cause potentially fatal complications such as infection and cancer relapse.

Venetoclax was based on a landmark discovery made in the 1980s by Walter and Eliza Hall Institute scientists that a protein called BCL-2 promoted cancer cell survival. It was approved for use by the Australian Therapeutic Goods Administration in 2017 and added to the Pharmaceutical Benefits Scheme in 2019 to treat CLL.

This study, Dr Davis says, has “repurposed” the wonder drug to improve outcomes and reduce side effects for those with AML, a rare but aggressive form of leukaemia, with a 27.4% survival rate.

When Venetoclax was combined with reduced radiation doses prior to transplant, over 80% of mice had a successful transplant, similar to mice receiving standard toxic radiation doses. “They stay healthy – they don’t get the side effects of high doses of radiation, they don’t get the inflammation, and the complications that we usually see.”