Ph-like signature
Another important new prognostic feature in ALL is the presence of the Ph-like signature, a gene expression signature that was initially described in children with poor-risk ALL, and which looks a lot like Ph-positive disease.
“When they delved in further, they identified that this signature actually correlated with multiple different [kinase] fusions ... and it turns out that 20%-25% of young adults have this signature,” she said.
Since event-free survival in young adults with ALL is usually in the 65%-70% range, most of the remaining 30%-35% likely have this signature, she explained.
The kinase fusions associated with the Ph-like signature retain intact tyrosine kinase domains, and the spectrum of the fusions changes across age groups.
Treatments targeting some of these – for example, dasatinib for patients with a Ph-like dasatinib-sensitive kinase mutation – are being investigated.
Additionally, the Children’s Oncology Group has developed a clinically adaptable screening assay to identify the signature, she noted.
“So I would say that, and there is probably some difference in opinion, it is now becoming fairly standard that at diagnosis in an adult with ALL we’re sending the Ph-like signature,” she said. “And again, usually you’re going to have to send this out, and at our center we send it out to [Nationwide Children’s Hospital] in Columbus [Ohio].”
As important as it is to identify the Ph-like signature, given its association with poor prognosis, a number of questions remain, including whether transplant improves outcomes.
“The hope is it probably does, and that’s something that’s being evaluated in studies,” she said, noting that clinical studies are also specifically targeting these patients.
“So these patients should probably be enrolled on a clinical trial, because their outcome is clearly inferior,” she said.
Dr. Advani reported consultancy for Pfizer; research funding from Genzyme, Novartis, Pfizer, and Sigma Tau; and honoraria from Genzyme, Pfizer, and Sigma Tau. She is also on the speakers bureau for Sigma Tau.