Real-World Data of Tisagenlecleucel Comparable With Clinical Trial Findings in Relapsed/Refractory B-Cell ALL

A population of patients with relapsed/refractory B-cell acute lymphoblastic leukemia was shown to benefit from tisagenlecleucel in practice compared to findings from the phase 2 ELIANA study.

Field data from tisagenlecleucel (Kymriah) administration in children and young adults with relapsed/refractory B-cell acute lymphoblastic leukemia appeared similar to findings from the phase 2 ELIANA trial (NCT02435849) plus a more favorable safety profile, according to a registry study presented at the 2021 American Society of Hematology Annual Meeting and Exposition.

Findings from this registry also showed that safety and efficacy outcomes were consistent in patients less than and older than 18 years of age.

In particular, tisagenlecleucel is “an autologous T-cell product directed against CD-19,” said Samuel John, MD, division chief of hematology/oncology and Distinguished Chair in Pediatric Oncology Research at UT Southwestern Medical Center in Dallas, Texas, during the presentation. “The T cells identify and kill the patient’s leukemia cells.”

In this non-interventional, prospective study, researchers analyzed data from the Center for International Blood and Marrow Transplant Research (CIBMTR) Registry of 561 patients up to 25 years of age with relapsed/refractory B-cell acute lymphoblastic leukemia.

“Acute lymphocytic leukemia is the most common cancer in children,” John said during the presentation. “This particular subtype, B-ALL, accounts for more than 80% of cases. While the majority of pediatric patients with B-ALL have excellent outcomes, approximately 15% to 20% of patients will relapse. The outcomes for these patients are poor, with a five-year survival estimated at approximately 50%. Treatment options in the relapsed setting include intensified chemotherapy regimens, stem cell transplantation and the use of novel immunotherapy, including chimeric antigen receptor T cells.”

All patients in this registry were treated with tisagenlecleucel after August 30, 2017 in the United States or Canada.

“Tisagenlecleucel was approved in 2017 for the treatment of pediatric and young adult patients up to 25 years of age with relapsed refractory B-ALL,” John explained in the presentation. “The CIBMTR is collecting data on these patients who received commercial tisagenlecleucel. Early real-world data for tisagenlecleucel from the CIBMTR registry reported similar efficacy to that in the ELIANA clinical trial with no new safety signals.”

Researchers performed age-specific analyzes in patients younger than (n = 389) and older than 18 years (n = 172) at the time of tisagenlecleucel administration. Efficacy was evaluated in patients with a follow-up of at least 12 months and included duration of response, best overall response from complete remission, relapse-free survival, event-free survival, and overall survival. Patients who completed the first assessment after 100 days were part of the safety evaluation in this study. There were several interesting side effects, including neurotoxicity and cytokine release syndrome, both of which were assessed by the ASTCT criteria.

Although most patient characteristics were similar at baseline, there were some factors that differed by age group. Patients aged 18 years and older had a greater burden of disease than patients younger than 18, as evidenced by lower rates of morphological complete remission and minimal residual disease egativity before infusion. In addition, older patients were more likely to be heavily pretreated before the infusion than the younger patients.

Efficacy in this study was assessed in 410 patients over a median of 25.9 months (range 12-43.6). The overall response rates in this registry were 86.8% compared to 82.3% in the ELIANA study. Minimal residual disease status information was available for 195 patients, 97.9% of whom were considered minimal residual disease negative.

The 12-month event-free survival in patients with available efficacy information was 52.6% compared to 57.2% in the ELIANA study. In addition, the duration of response at 12 months was similar in both studies (61.4% vs. 67.4%), respectively.

At 12 months, relapse-free survival was 62.5% compared to 66% in the ELIANA study. Both age groups had similar rates of relapse-free survival and overall survival.

Researchers assessed safety in 493 patients for a median of 23.9 months (range, 2-43.6). Most of the side effects of interest to the investigators were observed within the first 100 days after infusion. The safety outcomes in patients from the CIBMTR registry were more favorable than those from the ELIANA study.

“This may be related to a lower disease burden prior to T-cell infusion for patients treated with commercial tisagenlecleucel,” John said during the presentation.

From the registry, 22.9% had long-term neutropenia and 21.9% had long-term thrombocytopenia.

Safety data were broadly comparable between age groups, although more patients 18 years of age and older had a cytokine release syndrome or neurotoxicity. These side effects were then treated.

“Continuous collection of patient data in the CIBMTR registry will provide more insight into the use of tisagenlecleucel in practice,” concluded John.


John S, Pulsipher MA, Moskop A, et al. Realistic results for pediatric and young adult patients with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (ALL) treated with Tisagenlecleucel: update of the Center for International registry Blood and Marrow Transplant Research (CIBMTR). Presented at: 2021 ASH Annual Meeting & Exposition; Dec 9-14; Virtual. Summary 428

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