Tisagenlecleucel (Kymriah), a CD19-directed CAR T-cell therapy, is being adopted earlier in the treatment course for pediatric and young adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL). This shift is supported by data from a noninterventional, prospective study utilizing the Center for International Blood & Marrow Transplant Research (CIBMTR) registry, presented at the 2024 SOHO Annual Meeting. The findings indicate a change in treatment patterns and improved outcomes for this patient population.
Reduced Use in Later Relapses and Prior HSCT
Between 2018 and 2022, there was an 11% decrease in patients receiving tisagenlecleucel in their third or later relapse, according to the CIBMTR registry data. Concurrently, there was a 22% decrease in the rate of patients undergoing hematopoietic stem cell transplant (HSCT) before receiving the CAR T-cell therapy. This suggests that tisagenlecleucel is increasingly being used as a preferred option before resorting to HSCT.
Rayne Helen Rouce, MD, BS, of Baylor College of Medicine in Houston, Texas, the lead author of the study, stated that the incorporation of tisagenlecleucel has reduced the use of HSCT, even in high-risk populations, including patients under 3 years of age.
Decreased Disease Burden at Treatment
The study also revealed a 14% decrease from 2018 to 2022 in the rate of patients with high disease burden, defined as a bone marrow blast percentage of at least 50%, at the time of treatment. Among patients weighing 50 kg or less, there was a 10% decrease in those with high disease burden and a 15% decrease in those with intermediate disease burden (5% to 50% bone marrow blasts). For patients above 50 kg, the decrease in high disease burden was 18%.
Improved Morphologic Complete Remission Rates
Notably, the morphological complete remission (CR) rate increased by 17% from 2018 to 2022. "There was an increase in patients treated in morphologic CR over time, which is particularly notable because the pivotal trials leading to FDA approval excluded patients who did not have morphologic disease," Rouce said.
Impact on Post-Infusion HSCT Rates
Rates of post-infusion HSCT have also decreased since 2019, with a 22% decrease in patients under 3 years, a 7% decrease in patients between 3 and 18 years, and a 5% decrease in patients 18 years and older. Overall, 34.5% of patients received post-infusion HSCT.
Safety and Long-Term Outcomes
The median follow-up for efficacy was 33.3 months (interquartile range, 18.5-48.9). In evaluable patients (n = 785), the median overall survival (OS) was not estimable (95% CI, NE-NE) both with and without censoring for post-infusion HSCT. The 36-month OS probability with and without censoring was 66% (95% CI, 61-71) and 62% (95% CI, 57-66), respectively.
Rouce noted that long-term safety profiles remain favorable across age groups, consistent with previous reports, with a relatively low incidence of high-grade cytokine release syndrome (CRS). Grade 3 or higher CRS occurred in 16.2% of patients 18 years or older, 15.3% of patients younger than 18 years, and 7.2% of patients younger than 3 years. Grade 3 or higher neurological events occurred in 8.6%, 9.3%, and 10.1% of these respective age groups.
Future Directions
Rouce suggested that future studies should explore consolidative HSCT in patients who achieve remission after tisagenlecleucel, aiming to identify those at the highest risk of relapse and assess whether HSCT could improve outcomes in these patients.
