ASH 2018: ELIANA Trial: Tisagenlecleucel in Pediatric and Young Adult Patients With ALL
A single infusion of tisagenlecleucel (Kymriah) in pediatric and young adult patients with relapsed or treatment-resistant acute lymphocytic leukemia (ALL) continues to be highly effective in most patients, without the need for additional therapies. This latest analysis of the ELIANA trial results includes four additional patients and another year of follow-up. Results were presented by Grupp et al at the 2018 American Society of Hematology (ASH) Annual Meeting & Exposition (Abstract 895).
“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, in a statement. “We’ve shown that not only can we get these patients into remission, but they’re also going into remission with durable responses with [chimeric antigen receptor] CAR T [-cell therapy] alone—the majority of patients without any subsequent therapies, and with no minimal residual disease when we tested for evidence of leukemia.”
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 pediatric and young adult patients (up to 25 years) with relapsed or refractory B-cell ALL based on results from the multicenter, international ELIANA study.
ELIANA Details
Ninety-seven patients were enrolled in this single arm, open-label phase II study, which was conducted in 25 centers in 11 countries across North America, Europe, Australia, and Asia. Patients ranged in age from 3–24 (median age = 11 years] and received a median of three prior lines of therapy (eg, chemotherapy, radiation, or targeted therapy). A majority had undergone a previous hematopoietic stem cell transplant.
Findings
Among the 79 patients who were followed for 3 or more months after being infused with their reprogrammed CAR T-cell product, the overall response rate was 82%, and 62% of patients had a complete response. Researchers also reported that 66% of patients who had a complete response to CAR T-cell therapy were still in remission at 18 months. Additionally, infused patients had an overall survival rate of 70% at 18 months postinfusion. 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 Dr. Grupp.
Seventy-seven percent of patients experienced grade 3 or 4 cytokine release syndrome (CRS), with 48% these patients required treatment in the intensive care unit for a median of 7 days. All cases were ultimately reversed using the management algorithm developed for this study. The majority of key adverse events occurred in the first 8 weeks after infusion and included infection, low white blood cell and platelet counts, and neurologic events. No cases of cerebral edema were reported. Twenty-five deaths were reported after CAR-T infusion.
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.
This study was supported by Novartis.
Disclosure: See the study authors’ full disclosures at ash.confex.com.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
