17 Sep 2018

Congratulations to MRFF grant winners Andrew Spencer and Andrew Perkins!

Prof Andrew Spencer
Prof Andrew Perkins
Congratulations to Professors Andrew Perkins and Andrew Spencer, both of the Australian Centre for Blood Diseases, for their new funding under the Medical Research Future Fund (MRFF).

Professor Andrew Perkins' grant of $1.73M is for improving survival in myelofibrosis (MF) using genetic profiling. MF is a rare incurable blood cancer. It can develop from a pre-existing myeloproliferative disorder. Patients with high risk MF have a median survival of less than 3 years and some less than 5 years. The quality of life for patients is poor with a high symptom burden and frequent hospital admissions for blood transfusions and management of infections. About 50% of patients with MF carry the identical mutation in JAK2 (i.e. V617F) which drives the disease. Most of the other 50% carry mutations in other components of cytokine signalling pathways that activate JAK2.

The JAK1/2 inhibitor, ruxolitinib, is available in Australia on the PBS for treatment of high risk and Int-2 MF based primarily on two large phase 3 placebo controlled trials.

Most patients show initial clinical improvement but then slowly progress. There are no effective alternative drugs currently available in Australia. The molecular genetics of MF and MPNs has advanced greatly in the past 5 years. Many second mutations which adversely influence the risk of progression to acute leukaemia and impact on long term survival are now known. These mutations are mostly in epigenetic regulators. Genetic profiling of patients is becoming increasingly important for accurate prognosis and for personalized treatment options.

This grant will build a registry-linked national platform trial to improve precision-based outcomes, based on low cost genomic profiling, for patients with MF and using novel therapies.

Professor Andrew Spencer's grant of  $1,68M is for a trial in elderly myeloma patients to investigate treatment options. The full title of his study is "Frailty-stratified randomised controlled bayesian adaptive trial of bortezomib versus lenalidomide in transplant-ineligible myeloma - the FRAIL-M study".

Multiple myeloma (MM) is a low survival cancer, and is a heterogeneous, debilitating and incurable haematological cancer with a relative 5 year survival of 48.5%, the 14th worst 5 year relative survival out of 34 cancers. The population being studied in the FRAIL-M study are older patients with MM who have worse outcomes, with 5 year survival in those 65 year or older only 27% compared with 56% if less than 65 years.

The project will conduct a stratified randomised controlled trial to identify which competing treatment options are more appropriate in transplant-ineligible myeloma patients according to frailty status. It will enrol transplant-ineligible myeloma patients and stratify them into three groups (fit, intermediate-fit or frail) based on a standardised and validated frailty assessment. Each stratum will be randomised to a bortezomib-based vs a lenalidomide-based regimen, with dosing adjusted according to frailty stratum.

The co-primary endpoints are achievement of an overall response after four cycles of treatment and incidence of dose-limiting toxicity. Key secondary endpoints will include event-free survival, overall survival, infection and patient-reported outcome measure at baseline and following treatment. In each arm a Bayesian Optimal Phase II design will be used to jointly monitor efficacy and toxicity, and further adjust the dose or close individual treatment arms if they appear either too toxic or ineffective.

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