Two randomised trials have shown potential benefits of blinatumomab in children and young adults with high-risk first relapse of B cell acute lymphoblastic leukaemia.
The studies, both published in JAMA, also showed that use of the agent is likely to provide a less toxic option in those with chemotherapy-responsive disease. But only one of the studies achieved a statistically significant result and questions remain over timing, number of cycles and who benefits the most, an accompanying editorial pointed out.
In an international multi-centre trial led by researchers in Italy, patients aged 18 or under were randomised to one cycle of blinatumomab or chemotherapy after already receiving induction treatment and two cycles of consolidation chemotherapy.
The trial was stopped early due to positive results with data from 108 patients showing a 2-year estimate of the event-free survival rate of 66.2% in the blinatumomab group compared with 27.1% in the chemotherapy group.
Significant benefits of blinatumomab were noted in all subgroups and were particularly clear for patients relapsing less than 18 months from diagnosis, the researchers reported.
More patients in the blinatumomab group went on to have stem cell transplants than in the chemotherapy group (88.9% vs 70.4%) and there was a lower incidence of serious adverse events.
The second trial of 208 patients done at 155 hospitals across the US, Canada, Australia, and New Zealand included participants up to the age of 30. Patients in the study had a reinduction chemotherapy course but were then randomised to either two cycles of blinatumomab or two cycles of multiagent chemotherapy.
It was also terminated early because of better survival and lower toxicity rates favouring blinatumomab, but may have ended up underpowered as a result, the researchers reported in JAMA.
Blinatumomab was associated with a 2-year disease-free survival of 54%, compared with 39% in the chemotherapy arm, but that difference was not statistically significant.
“Chemotherapy has been used as primary consolidation treatment for ALL patients before receiving a stem cell transplant, despite this approach being only partially effective and associated with relevant toxicity,” said Prof Franco Locatelli, of the Sapienza University of Rome, who led the first study showing significant benefit. “[Blinatumomab] has now been shown to be a more effective and safer consolidation therapy option for children with high-risk first-relapse B-ALL.”
An editorial concluded that while these were the first randomised trials to “suggest that blinatumomab provides a more effective and less toxic therapeutic regimen,” the differences in their approach means there were still questions to answer.
“The improved outcomes, coupled with a favourable toxicity profile, support investigating the inclusion of blinatumomab and other immunotherapies in future clinical trials of front-line treatment and therapy for relapse among patients with childhood ALL.”