Reinfusion with tisagenlecleucel does not produce durable remissions in children or adolescents and young adults (AYAs) with B-cell acute lymphocytic leukemia (B-ALL), according to research presented at the 2023 Tandem Meetings.
In a retrospective study, more than half of these patients achieved minimal residual disease (MRD) negativity after reinfusion with tisagenlecleucel, but most patients ultimately relapsed.
“For the majority of patients, our data indicate that, if second infusion is used, plans for definitive therapy, such as stem cell transplant, should be made early, as response and remissions were not durable,” said study presenter Christa Krupski, DO, of the University of Cincinnati in Ohio. “Only a small minority of patients were able to avoid relapse and/or additional therapies.”
Dr Krupski and colleagues conducted this study in 42 children and AYAs with B-ALL. The patients’ median age at diagnosis was 8 (range, 0-25) years. The median age at first infusion with chimeric antigen receptor (CAR) T-cell therapy was 12.5 (range, 0-26) years.
The median time from first to second infusion of CAR-T cells was 173 (range, 52-521) days. Most patients (n=32) had at least 1 relapse prior to the second CAR T-cell infusion. All but 2 patients had received more than 1 line of treatment before the second CAR T-cell infusion, and 7 patients had received prior hematopoietic stem cell transplant (HSCT).
A total of 24 patients received tisagenlecleucel reinfusion for loss of B-cell aplasia while in ongoing complete response, and 17 patients received reinfusion for disease recurrence. A patient who received reinfusion for nonresponse was excluded.
The median follow-up was 496 (range, 150-1335) days. The overall rate of cytokine release syndrome (CRS) was 24%, and grade 3 or higher CRS occurred in 2% of patients. The overall rate of neurotoxicity was 7%, and the rate of grade 3 or higher neurotoxicity was 2%.
Of the 17 patients treated with tisagenlecleucel reinfusion after disease recurrence, 6 attained MRD negativity at day 28. Four of these patients relapsed, and 2 underwent HSCT. One HSCT recipient later relapsed, and the other died of complications.
The remaining 11 patients who were treated for disease recurrence had detectable disease at day 28. Five of these patients died of disease, 1 died of HSCT complications, and 1 died of infection.
Among the 24 patients treated with tisagenlecleucel reinfusion for loss of B-cell aplasia, 18 were MRD negative at day 28, and 6 had detectable disease at that point. Of the 6 with detectable disease, 3 were still alive and in remission at last follow-up, 2 died of disease, and 1 died of HSCT complications.
Of the 18 MRD-negative patients, 6 re-established B-cell aplasia. One of these patients did not receive subsequent therapy, 1 went on to HSCT, and 4 relapsed. There were 12 patients who did not re-establish B-cell aplasia. Four of these patients received no additional therapy, and 2 relapsed (1 of whom died). The remaining 6 patients underwent HSCT, 1 of whom relapsed, and 1 of whom died of complications.
The 1-year overall survival rate was 84%, and the 1-year event-free survival rate was 41%.
Disclosures: Dr Krupski reported having no disclosures.
Krupski C, Baggott C, McNerney KO, et al. Outcomes following tisagenlecleucel reinfusion in children and young adults with B-cell acute lymphocytic leukemia. Tandem Meetings 2023. February 15-19, 2023. Abstract LBA4.