A Peter Mac-led study has been selected as one of the 10 most outstanding manuscripts for 2017 by editors of the prestigious hematology journal Blood, strengthening our international reputation as a leader in blood cancer research.

Of the more than one thousand manuscripts published in 2017 in Blood, the Journal of the American Society of Hematology, the paper entitled “Promising efficacy and acceptable safety of venetoclax plus bortezomib and dexamethasone in relapsed/refractory MM” was selected as one of the best.

Peter Mac / RMH hematologist, Director of Clinical Aphaeresis and Myeloma Group Lead, A/Prof Simon Harrison, was the senior author on the study, involving an international team of researchers including from the Nantes University Hospital in France, AbbVie and Prof Andrew Roberts from the Walter and Eliza Hall Institute of Medical Research (WEHI).

The article reports the results of a phase Ib clinical trial combining a novel drug combination for the treatment of aggressive multiple myelomas (MM).

Despite recent advances in the treatment of MM, many patients inevitably relapse or become refractory to standard therapies.

Many MMs have increased levels of anti-apoptotic proteins that prevent the cancer cells from dying. Drugs that inhibit these proteins can trigger cell death, and are emerging as exciting new therapies for the treatment of blood cancers.

Here, researchers combined drugs targeting two different anti-apoptotic proteins, BCL-2 (venetoclax) and MCL-1 (bortezomib), along with a corticosteroid dexamethasone, in the treatment of 66 patients with relapsed/refractory MM.

They found that the drug combination resulted in high response rates, with 68% of participants having an overall response and over 40% of patients having a very good partial response or better. Significantly nearly 20% of patients had a complete response to the treatment.

“This study provides clear evidence that targeting anti-apoptotic proteins in myeloma is an important axis by which we can attack myeloma cancer cells,” explains A/Prof Harrison.

Importantly, the treatment regimen was well tolerated with manageable side effects.

The study also found that the treatment worked equally well in MMs that did or did not have a common t(11;14) DNA alteration, meaning more patients are likely to benefit from the new combination.

However, patients who had previously failed on bortezomib single agent therapy were less likely to respond to the combination treatment.

This study builds on the success of prior preclinical and clinical research demonstrating the efficacy and safety of venetoclax for the treatment of other blood cancers, including acute lymphoblastic leukemia (ALL), and the activity of bortezomib in MM cells, pioneered by researchers at WEHI and Peter Mac.

Blood is the most cited peer-reviewed publication in the field of hematology. To identify the top manuscripts of the year, editors of the journal considered the quality of the work and interest to the field of hematology.

“To be listed as one of the top ten articles in Blood during 2017 is a real honour for all of the investigators who participated in this important study,” says A/Prof Harrison.