CTL019 CAR T-Cell Therapy Strides Towards Approval in Pediatric and Young Adult Patients With ALL

Virginia Powers, PhD
Published: Sunday, Jun 25, 2017

Stephan A. Grupp, MD, PhD
Stephan A. Grupp, MD, PhD
CTL019, an investigational chimeric antigen receptor (CAR) T-cell therapy, demonstrated high response rates and a manageable safety profile in pediatric and young adult patients with relapsed and/or refractory (r/r) acute lymphoblastic leukemia (ALL), according to updated results from a global registration trial presented during the 2017 European Hematology Association (EHA) Congress in Madrid.

The potential for CTL019 in the treatment of children and young adults with r/r ALL was supported by updated data demonstrating an overall remission rate of 83% (95% CI, 71-91; P <.001) at 3 months post-infusion, thus meeting the primary endpoint of the study.

“The ELIANA trial is the first global multicenter trial of a CAR T-cell therapy," noted Stephan A. Grupp, MD, PhD, the Yetta Deitch Novotny Professor of Pediatrics at the Perelman School of Medicine at the University of Pennsylvania and director of translational research in the Center for Childhood Cancer Research at the Children's Hospital of Philadelphia, who presented the findings.

Grupp explained that CTL019 was manufactured from leukapheresed autologous peripheral blood T cells at a centralized manufacturing facility in the United States but was delivered to patients worldwide at 25 sites across North America, Europe, and Asia-Pacific. “Each site has a training program specific for CTL019 logistics and patient management,” he said. ELIANA is an ongoing single-arm, open-label, multicenter, global, phase II study that has enrolled 88 pediatric/young adult patients with CD19-positive r/r B-cell ALL and with ≥5% bone marrow lymphoblasts by morphology.

The analysis included 68 infused patients; 4 patients (5%) are currently pending infusion currently, 7 (8%) had manufacturing failures, and 9 (10%) were not infused due to death or adverse events (AEs). All 68 patients were infused with a single dose at a median of 3.0×106 (range, 0.2-5.4×106) transduced CTL019 cells/kg.

The median age was 12 years (range, 3-23), 56% of patients were male, and 59% of patients had received prior allogeneic stem cell transplant. Patients had received a median of 3 lines of therapy (range, 1-8). Twenty-one percent of patients were refractory to prior treatment and 79% of patients had relapsed. High-risk genetic lesions were identified in 29% of patients and 9% had Down syndrome.

The primary endpoint was overall remission rate, including complete remission (CR) plus CR with incomplete blood count recovery (CRi) within 3 months of infusion. Secondary endpoints included duration of remission (DOR), overall survival (OS), safety, and cellular kinetics.

The CR rate was 63% and CRi was 19%; the best overall response of CR or CRi with minimal residual disease (MRD)-negative bone marrow was 83% within 3 months of infusion.

Median OS was 16.6 months; 6-month OS rate was 89% (95% CI, 77-94) and OS rates at 9 and 12 months were 79% (95% CI, 63-89). The median OS follow-up was 6.4 months and the maximum follow-up was 17.6 months to date.

CTL019 produced long-term remission with 75% of patients achieving 6-month relapse-free survival (RFS; 95% CI, 57-87), and 64% of patients attaining 9 and 12 month RFS (95% CI, 42-79). The median duration of response was not reached.

The safety analysis included all 68 infused patients and revealed that the majority of AEs occurred during the first 8 weeks post CTL019 infusion; grade 3/4 AEs occurred during the first 8 weeks in 82% of patients and after 8 weeks in 39% of patients. At any time during the study, 85% of patients experienced grade 3/4 AEs, of which 72% were determined treatment-related.

The most commonly reported grade 3/4 AEs (in ≥15% of patients) included febrile neutropenia (34%/3%), hypotension (12%/10%), aspartate aminotransferase increase (12%/4%), hypokalemia (12%/3%), and hypoxia (12%/6%). Cytopenias of any grade that did not resolve by day 28 were seen in 37% of patients, and were grade 3 in 15% and grade 4 in 18% of patients. Grade 3/4 infections occurred in 24%/3% of patients. Grade 3 tumor lysis syndrome was reported in 4 patients.

Cytokine release syndrome (CRS) of all grades occurred in 78%, grade 3 in 21%, and grade 4 in 27% of patients. The mean duration of CRS was 8 days (range, 1-36), and the time to onset of CRS was 3 days (range, 1-22). Admission to an intensive care unit was required for 46% of patients with CRS; 38% received anti-cytokine therapy, 25% received vasopressors, 15% required intubation, and 10% of patients required dialysis. Intervention for hypotension was necessary in 51% of CRS patients. No CRS-associated deaths occurred.

“CRS was manageable at all sites by appropriately trained staff,” said Grupp.

Grade 3 neurological AEs occurred in 15% of patients, but no grade 4 events occurred and no cerebral edema was reported. The most common any-grade neurological events were encephalopathy (12%), confusional state (10%) and delirium (10%).


View Conference Coverage
Online CME Activities
TitleExpiration DateCME Credits
Oncology Best Practice™: Choosing Therapies for Patients with EGFR-Mutant Lung Cancers: More Options... More Decisions... Better OutcomesFeb 28, 20182.0
Clinical Vignette Series: 34th Annual Chemotherapy Foundation Symposium: Innovative Cancer Therapy for Tomorrow®Feb 28, 20182.0
Publication Bottom Border
Border Publication
x