Higher CAR-T dose associated with longer remission among younger patients with ALL
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Children and young adults with acute lymphoblastic leukemia who received higher doses of tisagenlecleucel achieved significantly longer OS and RFS, according to study results presented at TCT Meetings Digital Experience.
Researchers observed the relationship between dose and survival outcomes only among patients who responded to therapy with tisagenlecleucel (Kymriah, Novartis), an autologous, gene-edited, CD19-directed chimeric antigen receptor T-cell therapy.
“Because there is such a wide range of doses for tisagenlecleucel, we wanted to see if survival rates were dependent on dose,” Heather E. Stefanski, MD, PhD, associate professor of pediatrics in the division of blood and marrow transplant & cellular therapy at University of Minnesota School of Medicine, told Healio. “Patients who were given higher doses of CAR T cells had better overall survival and relapse-free survival.”
Stefanski and colleagues used retrospective data from the Pediatric Real World CAR Consortium, which includes 15 member institutions that provide CAR T-cell therapy in the U.S.
The study cohort included 185 children and young adults who received commercial tisagenlecleucel for relapsed or refractory ALL. Patients typically receive between 0.2 × 106 and 5 × 106 CAR T cells per kilogram of body weight if they weigh up to 50 kg and 0.1 × 108 to 2.5 × 108 CAR T cells/kg if they weigh more than 50 kg.
Among 184 patients eligible for survival analysis, 156 achieved complete response to therapy as determined by evaluation at 28-day follow-up, 23 did not respond to therapy and five died before the 28-day follow-up.
Stefanski and colleagues divided patients who responded to therapy into the following dose quartiles to evaluate the impact of CAR T-cell dose: less than 1.31 × 106; 1.31 × 106 to 1.69 × 106; 1.7 × 106 to 2.4 × 106; and greater than 2.4 × 106.
The researchers found that tisagenlecleucel dose did not differ significantly between patients who achieved complete response to therapy by day 28 and those who did not respond to therapy. The median cell dose among patients who responded to therapy was 1.7 × 106 CAR T cells/kg (range, 0.134 × 106-7.49 × 106).
Patients in the highest-dose group achieved significantly longer OS and RFS than patients in the lowest-dose group (P for both = .0033).
Stefanski told Healio that her group’s analysis showed no differences in neurotoxicity and overall or grade 3 or greater cytokine release syndrome among the dose groups.
If further study validates the results, patients may benefit from having larger doses of the CAR-T product, she added. This could include providing more than one dose of CAR T cells to patients during infusion to promote longer-lasting remissions.
Further study is planned via a prospective trial that will examine the effects of CAR T-cell dosage — in addition to several characteristics of the CAR T cells themselves — on outcomes among pediatric patients in a real-world setting, Stefanski said.
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Stefanski HE, et al. Abstract LBA9. Presented at: The 2021 TCT Meetings Digital Experience (virtual meeting); Feb. 8-12, 2021.
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