A single infusion of tisagenlecleucel in paediatric and young adult patients with relapsed or treatment-resistant acute lymphocytic leukaemia (ALL) continues to be highly effective in fighting cancer in most people, without the need for additional therapies.
This latest analysis of the ELIANA trial results includes four additional patients and another year of follow up.
“These are patients who weren’t eligible for transplant, or who had relapsed after transplant; none were in remission and no other treatments were available at the time they entered the trial,” said lead study author Stephan A. Grupp, MD, PhD, of the Children’s Hospital of Philadelphia. “We’ve shown that not only can we get these patients into remission, but they’re also going into remission with durable responses with CAR-T alone – the majority of patients without any subsequent therapies, and with no minimal residual disease when we tested for evidence of leukaemia.”
These most recent data continue to validate the benefits of using this new treatment paradigm in this patient population, Dr. Grupp added.
Over the last year, tisagenlecleucel has been approved by the U.S. Food and Drug Administration (FDA), as well as by health authorities in the EU, Switzerland, and Canada for the treatment of paediatric and young adult patients (up to 25 years) with relapsed or refractory B-cell ALL based on results from the multi-centre, international ELIANA study.
Ninety-seven patients were enrolled in this single arm, open-label phase II study, which was conducted in 25 centres in 11 countries across North America, Europe, Australia, and Asia.
Patients ranged in age from 3-24 and received a median of three prior lines of therapy (e.g., chemotherapy, radiation, or targeted therapy).
A majority had undergone a previous haematopoietic stem cell transplant.
Among the 79 patients who were followed for three or more months after being infused with their reprogrammed CAR-T product, 82 percent achieved a complete remission.
Researchers also reported that 66 percent of patients who had a complete response to CAR-T were still in remission at 18 months.
Additionally, the majority of the infused patients were still alive (overall survival of 70 percent) at 18 months post-infusion.
Even in this updated analysis, median overall survival has not been reached.
Another success, according to researchers, is that the many centres in the study have been able to safely and consistently administer CAR T-cell therapy.
“We see relatively similar results across study sites — even with centres with no prior experience administering CAR T-cell therapy — so we’ve shown we can roll this out, do it safely, and promulgate appropriate approaches to toxicity management as well,” said Dr. Grupp.
Seventy-seven percent of patients experienced grade 3 or 4 cytokine release syndrome (CRS), which is triggered by an over-reactive immune response.
Nearly half of these patients required treatment in the intensive care unit for a median of seven days.
All cases were ultimately reversed using the management algorithm developed for this study.
The majority of key adverse events occurred in the first eight weeks after infusion and included infection, low white blood cell and platelet counts, and neurological events.
No cases of cerebral edema were reported.
Twenty-five deaths were reported after CAR-T infusion, mostly due to disease progression and other causes unrelated to CAR T-cell therapy.
Dr. Grupp said the prevalence of adverse events remains unchanged from previous analyses and there is ongoing evidence that CAR-T is benefiting patients well after a year.
Further follow-up of patients is ongoing in the ELIANA trial.