Venetoclax, a breakthrough cancer treatment, is driving a major shift in the management of a range of blood cancers, with two new clinical trials of chemotherapy-free combinations demonstrating dramatic benefits for patients with hard-to-treat leukaemia and lymphomas.
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, involving patients whose blood cancer had relapsed or was resistant to conventional treatment, used venetoclax in combination with another targeted drug. 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,” said 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 trialled 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,” said 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.” 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.
“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,” said 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.
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. Thanks to the generosity of ACRF supporters, ACRF contributed significantly to the success of the early phases of research into venotoclax.
This news was first posted on the Peter Mac website. Image of Professor Seymour provided by Peter Mac.