Pivotal CAR T-Cell Data Reported in Relapsed/Refractory B-Cell ALL

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Stephan Grupp, MD, PhD

Stephan Grupp, MD, PhD

UPDATED RESULTS from the ELIANA clinical trial of CTL019 (tisagenlecleucel)—an investigational chimeric antigen receptor (CAR) T-cell therapy—found that remission rates are maintained at 6 months in relapsed/refractory pediatric and young adult patients with B-cell acute lymphoblastic leukemia. These data from this pivotal trial of CTL019 show that 83% of patients (52 of 63; 95% confidence interval [CI] = 71%–91%) achieved complete remission or complete remission with incomplete blood cell count recovery within 3 months of infusion. No minimal residual disease was detected among responding patients. These results were presented at the 2017 European Hematology Association Annual Meeting in Madrid.

First Pediatric Global CAR T-Cell Registration Trial 

ELIANA IS THE FIRST pediatric global CAR T-cell therapy registration trial, with study enrollment having occurred across 25 centers in the United States, Canada, European Union, Australia, and Japan. The single-arm, open-label, multicenter phase II study included patients aged 3 to 23 years who were primary refractory, refractory to chemotherapy after their first relapse, relapsed after second-line therapy, or ineligible for an allogeneic stem cell transplant. Patients in the trial received a median of three prior lines of therapy, and 59% of patients had a prior stem cell transplant. 

The ELIANA study also showed that the relapse-free probability was 75% (95% CI = 57%–87%; median duration of response not reached) at 6 months and 64% (95% CI = 42%–79%) at 12 months among responders. In addition, the probability of survival was 89% (95% CI = 77%–94%) at 6 months and 79% (95% CI = 63%–89%) at 12 months. The median time from infusion to data cutoff was 8.8 months. 

“Durability is an important measure for children and young adults with relapsed or refractory B-cell ALL, and we are truly encouraged by the results of this study.”
— Stephan Grupp, MD

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Response Rates Durable 

“THE UPDATED CTL019 ELIANA DATA illustrating early observed response rates that have held steady over 6 months’ time are exciting findings. Durability is an important measure for children and young adults with relapsed or refractory B-cell ALL, and we are truly encouraged by the results of this study,” said lead investigator Stephan Grupp, MD, PhD, the Yetta Deitch Novotny Professor of Pediatrics at the Perelman School of Medicine at the University of Pennsylvania, and Director of the Cancer Immunotherapy Frontier Program at the Children’s Hospital of Philadelphia. 

The ELIANA trial enrolled 88 patients. Of them, 16 patients discontinued treatment before infusion and the majority (9 patients) did so due to rapid progression of their disease or deterioration in their clinical status. This reflects the acute and progressive nature of this disease. Of the 16 patients who were not infused, 7 of these were a result of insufficiently formulated CAR-T cell product. Additionally, 5 infused patients had not reached 3-month follow-up and four patients were pending infusion at the time of data cutoff. 

Cytokine-Release Syndrome 

AMONG THE PATIENTS in the ELIANA trial, 47% experienced grade 3 or 4 cytokine release syndrome, a known complication of the investigational therapy that may occur when the engineered cells become activated in the patient’s body. This adverse reaction was managed globally using prior site education on implementation of the cytokine-release syndrome treatment algorithm. There were no deaths due to refractory cytokine-release syndrome, and no incidents of cerebral edema were reported. Grade 3 neurologic events were reported in 15% of patients; no grade 4 events were seen. 

Editor’s note: On July 12, 2017, the Oncologic Drugs Advisory Committee of the U.S. Food and Drug Administration voted unanimously in favor of CTL019 (tisagenlecleucel) for the treatment of relapsed or refractory pediatric and young adult patients with B-cell acute lymphoblastic leukemia. 

DISCLOSURE: Dr. Grupp reported no conflicts of interest. 


1. Buechner J, Grupp SA, Maude SL, et al: Global registration trial of efficacy and safety of CTL019 in pediatric and young adult patients with relapsed/ refractory acute lymphoblastic leukemia: Update to the interim analysis. European Hematology Association Annual Meeting. Abstract S476. Presented June 24, 2017.

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