High success rate
Of the 27 patients infused, 17 had sufficient cells harvested in a single day, and the remainder required 2-4 days. As noted, the CAR T product was successfully manufactured in 28 patients, with a median dose of 2.3 x 106/kg of patient weight.
The treatment failed for 2 of the 26 efficacy-evaluable patients, resulting in an MRD-negative rate of 92%.
Event-free survival at 6 months was 67%, similar to that in ELIANA (73%), and the 12-month event-free survival was 58%, which was superior to that in ELIANA (50%).
The 6-month and 12-month overall survival rates among the younger children were identical at 88%, compared with 90% and 76%, respectively, in ELIANA.
The 6- and 12-month probability of ongoing B-cell depletion, indicating CAR T persistence, were 77% and 68%, respectively. In ELIANA, the 6-month probability of B-cell depletion was 83%.
A total of 10 of the 27 patients received further therapy, including 3 who were given maintenance therapy for poor CAR T persistence, 2 who underwent chemotherapy for relapse, and 5 who underwent allogeneic stem cell transplant.
Of six patients who experienced a relapse after having a complete response, two had CD19 relapse.
Low rate of serious CRS
At 30 days post infusion, grade 3 or greater cytokine release syndrome (CRS) had occurred in two patients, severe neurotoxicity occurred in one, and grade 3 or greater prolonged cytopenias occurred in eight patients.
The toxicity profile in this study was generally favorable in comparison with ELIANA, with shorter median duration of CRS, shorter median duration of CRS-related ICU stay, and a lower frequency of tocilizumab use. It should be noted, however, that the I-BFM investigators used American Society for Transplantation and Cellular Therapy CRS consenus criteria, whereas the ELIANA investigators used University of Pennsylvania criteria.
“If the longer-term follow-up data are encouraging, it might suggest that the outcomes from tisagenlecleucel therapy are comparable to that of stem cell transplantation in high-risk relapsed infant ALL, without the associated late effects, and possibly supports CAR T-cell therapy eventually replace stem cell transplantation in this setting,” Dr. Ghorashian said.
Dr. Curran, who leads the CAR T effort at MSK Kids, the children’s division of MSKCC, agreed that the goal is for CAR T to replace stem cell transplants.
“I hope I put my clinical practice out of business with my research practice,” he said, but added that “I think we need to do more research in figuring out how to best use CAR T cells, either earlier, or as some data suggest, by treating patients with lower disease burden we would get better durability.
“Because obviously in kids’ cancer one relapse is too much, and we want to be able to raise that bar and provide hope and a cure for all of our children,” he said.
The study was sponsored by the I-BFM Resistant Disease Committee and member institutions. Dr. Ghorashian disclosed advisory board activity for Novartis, maker of tisagenlecleucel, and patents and royalties from UCL Business. Dr. Curran research funding and consulting fees from Novartis.