Tisagenlecleucel Responses in Pediatric ALL Sustained With Longer Follow-up


At a median follow-up of 13.1 months, tisagenlecleucel (Kymriah) induced an overall remission rate of 81% in children and young adults with relapsed/refractory B-cell acute lymphoblastic leukemia.

Shannon L. Maude, MD, PhD

Shannon L. Maude, MD, PhD

Shannon L. Maude, MD, PhD

At a median follow-up of 13.1 months, tisagenlecleucel (Kymriah) induced an overall remission rate of 81% in children and young adults with relapsed/refractory B-cell acute lymphoblastic leukemia (ALL).1

In an analysis of 75 infused patients with 3 or more months of follow-up, 60% of patients achieved complete remission (CR) and 21% of patients achieved CR with incomplete blood count recovery (CRi) following tisagenlecleucel infusion. By day 28, investigators detected no minimal residual disease (MRD) among responding patients.

Updated results from the pivotal phase II ELIANA clinical trial were published today in the New England Journal of Medicine. Based on the initial data from the ELIANA trial, the FDA approved the chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel, which was developed by the University of Pennsylvania and Novartis, for use in this patient population in August 2017.

“This expanded, global study of CAR T-cell therapy gives us further evidence of how remarkable this treatment can be for our young patients in whom all other treatments failed,” lead author Shannon L. Maude, MD, PhD, a pediatric oncologist at Children’s Hospital of Pennsylvania (CHOP) and assistant professor of Pediatrics in the Perelman School of Medicine at the University of Pennsylvania, said in a press release. “Our data show not only can we can achieve longer-term durable remissions, and longer-term survival for our patients, but that these personalized, cancer-fighting cells can remain in the body for months or even years, effectively doing their job.”

ELIANA, the first pediatric global CAR-T cell therapy registration trial, is a single-cohort, multicenter, study of tisagenlecleucel in children and young adults with relapsed or refractory B-cell ALL. Patients aged 3 to 21 years with least 5% lymphoblasts in bone marrow at screening received a single median weight-adjusted dose of 3.1 × 106 transduced viable T cells per kg of body weight. The median total dose of transduced cells was 1.0 × 108 (range, 0.03 × 108 to 2.6 × 108).

Event-free survival was 73% at 6 months (95% CI, 60-82) and 50% at 12 months (95% CI, 35-64) among the 61 patients who responded to treatment. Overall survival (OS) in all 75 patients was 90% (95% CI, 81-95) at 6 months and 76% (95% CI, 63-86) at 12 months.

Investigators detected CAR T-cells in patients up to 20 months after initial infusion, with a median persistence of 168 days (range, 20-617) at data cutoff. All patients in the trial received a single infusion of tisagenlecleucel.

All responding patients demonstrated B-cell aplasia, an on-target effect of treatment with tisagenlecleucel. Evaluable patients with a response at day 28 had a median time to maximum expansion of 10 days (range, 5.7-28). Six patients with no response had a median time to maximum expansion of 20 days (range, 13-63).

Nearly all patients (95%) experienced any-grade treatment-related adverse events (TRAE). The most common non-hematologic TRAEs were cytokine release syndrome (CRS; 77%), pyrexia (40%), decreased appetite (39%), febrile neutropenia (36%) and headache (36%).

Three-quarters of patients experienced a grade 3/4 TRAE, including 21% who experienced grade 3 CRS and 25% who experienced grade 4. Investigators managed CRS using prior site education on implementation of the CRS treatment algorithm. Thirty-five (47%) patients were admitted to the intensive care unit for management of CRS.

Forty percent of patients experienced neurological events within 8 weeks of infusion. Ten patients (13%) had grade 3 neurological events that were managed with best supportive care. There was no incidence of grade 4 neurological events or cerebral edema reported.

“One of our more challenging questions, ‘Can we manage the serious side effects of CAR T-cell therapy?’ was asked and answered in this global study,” coauthor Stephan A. Grupp, MD, PhD, said in a press release. Grupp is the director of the Cancer Immunotherapy Frontier Program at CHOP. “Some of our patients get very sick, but we showed that most toxic effects can be short-lived and reversible, with the potential for our patients to achieve durable, complete remissions. That's a pretty amazing turnaround for the high-risk child who, until now, had little chance of surviving.”

In ELIANA results presented in September at the 2017 SOHO Annual Meeting, the overall response rate was 83%, which included CRs with complete hematologic recovery in 63% of patients and CRi in 19%.2 Additionally, 83% of patients met the secondary endpoint of CR with or without complete recovery within 3 months with MRD-negative bone marrow.

Among all infused patients, the relapse-free survival rate was 75% at 6 months and 64% at 9 and 12 months. OS was 89% at 6 months and 79% at 9 and 12 months. Median OS was 16.6 months.


  1. Maude SL, Laetsch TW, Buechner J, et al. Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia. N Engl J Med. 2018; 378:439-448.
  2. Pulsipher M, Buechner J, Grupp SA, et al. Global registration trial of efficacy and safety of CTL019 in pediatric and young adult patients with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL): update to the interim analysis. Presented at 2017 SOHO Annual Meeting. Abstract ALL-152.
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