Stem Cell Transplant Plus CAR-T Improves Leukemia-Free Survival in Young Patients With ALL

According to a phase 1/2 trial, hematopoietic cell transplant (HCT) in young patients with acute lymphoblastic leukemia (ALL) who had experienced chimeric antigen receptor (CAR) T-cell induced remission, followed by functional persistence of remission for 63 days or less, significantly improved leukemia-free survival (LFS) outcomes (P = .01) versus watchful waiting, even if they had a prior HCT.

“It is evident from the early CD19 CAR T-cell trials for (B cell acute lymphoblastic leukemia) B-ALL that a subset of patients can be cured with no additional therapy, and because HCT is associated with significant risk of short- and long-term morbidity, avoidance of HCT is a frequent goal,” wrote lead author Corinne Summers, MD, Seattle Children’s Research Institute, and colleagues.

Although many patients achieve an initial complete remission (CR) from CAR-T therapy, half of them had disease recurrence within 6 to 18 months after infusion.

“Although our data suggest that HCT may improve outcomes, there are associated long-term effects of HCT, impacting development of the pediatric patient. Therefore, avoiding HCT is an important goal to mitigate long term morbidity,” the co-authors wrote.

In the phase 1 and 2 portion of the Pediatric and Young Adult Leukemia Adoptive Therapy (PLAT-02) study, 64 patients received a 41BB-CD19 CAR T-cell product. Of these, 14 patients did not achieve remission, relapsed, or died.

Out of the 58 subjects (91%) who achieved a minimal residual disease (MRD)-negative CR, the LFS at 1 year was 67% (95% CI, 56%-81%), and the estimated median time to relapse or death following SCRI-CAR19 infusion was 21 months (95% CI, 14 months-NA).

Of 32 subjects who experienced relapse after achieving a CR, 18 (56%) developed CD19+ recurrence, at a median of 12 months post-CAR T-cell infusion (range, 1-27 months), and 14 (44%) developed CD19 recurrence (antigen escape), at a median of 8 months post-CAR T-cell infusion (range, 1-42 months).

Source:
Summers C, Wu Q, Annesley C, et al. Hematopoietic Cell Transplantation after CD19 Chimeric Antigen Receptor T Cell-Induced Acute Lymphoblastic Leukemia Remission Confers a Leukemia-Free Survival Advantage. Transplant Cell Ther. 2022 Jan;28(1):21-29.