The latest analysis of the ELIANA trial after another year of follow up revealed that a single infusion of tisagenlecleucel in pediatric and young adult patients with relapsed or treatment-resistant acute lymphocytic leukemia (ALL) continues to be highly effective in fighting cancer in most people, without the need for additional therapies.
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 pediatric and young adult patients (up to 25 years) with relapsed or refractory B-cell ALL based on results from the multi-center, international ELIANA study. The latest analysis of the study has been presented at the ASH conference.
97 patients were enrolled in the single arm, open-label phase II study ELIANA, which was conducted in 25 centers 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 hematopoietic 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% achieved a complete remission. 66% 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%) 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 centers 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 centers 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 lead study author Stephan A. Grupp, MD, PhD, of the Children’s Hospital of Philadelphia.
77% 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. 25 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.
Grupp S et al.: Updated analysis of the efficacy and safety of tisagenlecleucel in pediatric and young adult patients with relapsed/refractory acute lymphoblastic leukemia. ASH Annual Meeting 2018, abstract #895