Minister Hennessy with patients and doctors
05 April 2018
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A breakthrough drug with its origins in Melbourne is driving a major shift in the treatment of a range of blood cancers, with two new clinical trials of chemotherapy-free combinations demonstrating dramatic benefits for patients with hard-to-treat diseases.

Venetoclax is a targeted drug in tablet form that was developed based on scientific discoveries made at the Walter and Eliza Hall Institute of Medical Research, and Melbourne researchers from the Peter MacCallum Cancer Centre (Peter Mac) and The Royal Melbourne Hospital (RMH) continue to lead many of the ongoing clinical trials.

Results of two new venetoclax trials – the MURANO Study involving patients with Chronic Lymphocytic Leukaemia (CLL) and AIM Study in Mantle-Cell Lymphoma (MCL) – were recently published in the New England Journal of Medicine.

Both trials involved patients whose blood cancer had relapsed or was resistant to conventional treatment, used venetoclax in combination with another targeted drug, and these treatment combinations resulted in high rates of patients with no detectable cancer.

“That venetoclax is able to produce such dramatic results in this hard-to-treat patient group is remarkable, and has led to much excitement among blood cancer clinicians globally and the research community particularly in Melbourne where this drug was pioneered,” says Professor John Seymour, Director of Haematology at Peter Mac and RMH.

“The data shows venetoclax should replace chemotherapy altogether in patients with advanced forms of CLL – a practice-changing result which will rapidly translate into the standard of care globally.”

The MURANO study, led by Prof Seymour, involved 389 patients across 109 international trial sites and compared venetoclax plus rituximab to standard immuno-chemotherapy (bendamustine plus rituximab).

Venetoclax treatment was found to more than double the likelihood that CLL patients would live for two years without their cancer recurring (84.9% vs 36.3%), and the proportion of patients who had very few or no detectable leukemia cells in their blood was 83.5%, compared with 23.1% of patients who received standard immune-chemotherapy treatment.

The AIM study, led by Peter Mac’s A/Professor Constantine Tam and trialed at both Peter Mac and RMH, involved 24 patients with MCL. They were treated with venetoclax plus ibrutinib – two drugs expected to have an improved synergistic effect. This was the first ever trial of this scientifically-designed chemotherapy-free combination. Most (71%) patients went on to show no detectable cancer, and 78% of these patients remained cancer free for at least 15 months.

“This was in patients who we expected to have a poor outcome on conventional therapy, and in which treatment with either ibrutinib or venetoclax alone was expected to see only 21% of patients show a complete response,” says A/Prof Tam.

“These very promising results have triggered additional and larger studies to better understand the synergistic benefits of the venetoclax-ibrutinib treatment combination in MCL patients.”

For patients Chris and Sharon, who were both diagnosed with Mantle Cell Lymphoma in 2012, being a part of the AIM study has been life-changing.

“I went on the (AIM) trial and happy days,” says Chris, who has had a remarkable result after this cancer was initially controlled after treatment with chemotherapy and a stem cell transplant, but returned again in 2016.

“In term of what the scans say, I’m cancer free.”

Sharon also received chemotherapy and a stem cell transplant, and her cancer was then in remission for two years.

“It came back in my tonsils – I noticed one of my tonsils was swollen and wasn’t going down,” she says.

The cancer was also detected in her lymph nodes. Sharon joined the AIM study and has had a very positive result with even the most sensitive of tests unable to find a trace of cancer.

CLL is the most common form of leukaemia in Australia, with around 1000 people diagnosed with the cancer every year. MCL is an uncommon sub-type of lymphoma which is considered incurable in most patients with conventional chemotherapy treatments.

Venetoclax was developed based on a landmark discovery made in Melbourne during the late 1980s by Walter and Eliza Hall Institute scientists, that a protein called BCL-2 promoted cancer cell survival.

“The development of venetoclax - from basic science through to international clinical trials with practice-changing results - provides a strong example of how Australian cancer researchers and clinicians can lead the world,” says Professor Andrew Roberts, a clinical haematologist at RMH and Peter Mac, researcher at the Walter and Eliza Hall Institute and University of Melbourne, and co-designer of the AIM study.

“Venetoclax selectively targets BCL-2, essentially causing cancerous cells to simply melt away, in many instances.”

The rapidity of this “melting away” can also be problematic for patients leading to the side-effect of tumour lysis syndrome. This affected six patients in the MURANO Study and two in the AIM Study, but was managed safely in all cases.

The RMH (Melbourne Health), Peter Mac and the Walter and Eliza Hall Institute are three of the ten organisations which make up the Victorian Comprehensive Cancer Centre (VCCC) collaborative, a powerful partnership committed to cancer research, treatment and care.

Pictured left to right: A/Prof Constantine Tam, Prof Andrew Roberts, The Hon Jill Hennessy MP, trial patients Sharon and Chris and Prof John Seymour.

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