In a long-term follow-up of a National Cancer Institute (NCI) phase I trial reported in the Journal of Clinical Oncology, Nirali N. Shah, MD, and colleagues found that autologous CD19 chimeric antigen receptor (CAR) T-cell therapy followed by allogeneic hematopoietic stem cell transplantation can produce prolonged disease control in a substantial proportion of children and young adults with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL).
As stated by the investigators, “CD19-CAR T cells induce high response rates in children and young adults with B-cell ALL, but relapse rates are high. The role for allogeneic hematopoietic stem cell transplant following CD19-CAR T-cell therapy to improve long-term outcomes in children and young adults has not been examined.”
Nirali N. Shah, MD
Study Details
The study was a phase I dose-escalation study in which 50 children and young adults with relapsed or refractory B-cell ALL at the NCI Pediatric Oncology Branch received autologous CD19.28ζ-CAR T cells. The two dose levels investigated consisted of single doses of 1 x 106 CAR T cells/kg and 3 x 106 CAR T cells/kg. Patients had a median age of 13.5 years (range = 4.3–30.4 years), had been treated with a median of four prior regimens (range = 1–16), 22% had primary refractory disease, and 44% had undergone prior hematopoietic stem cell transplant.
Key Findings
Complete remission was achieved in 31 patients (62.0%); among these 31 patients, 28 (90.3%) were minimal residual disease (MRD)-negative on flow cytometry.
Complete remission was achieved in 29 (69%) of 42 patients who received fludarabine/cyclophosphamide–based lymphodepletion vs 2 (25%) of 8 who received non–fludarabine/cyclophosphamide–based lymphodepletion (P =.041).
At a median follow-up of 4.8 years (range = 3.5–7.2 years), median overall survival in the entire cohort was 10.5 months (95% confidence interval [CI] = 6.3–29.2 months) and median event-free survival was 3.1 months (95% CI = 0.9–7.7 months). Receipt of fludarabine/cyclophosphamide–based lymphodepletion was associated with improved overall and event-free survival.
Among 28 patients achieving MRD-negative complete remission, 21 (75.0%) had consolidating allogeneic hematopoietic stem cell transplant (including 4 with prior hematopoietic stem cell transplant). Among those with undergoing allogeneic hematopoietic stem cell transplant, median overall survival was 70.2 months (95% CI = 10.4 months–not estimable), cumulative incidence of relapse was 9.5% (95% CI = 1.5%–26.8%) at 2 years, and 5-year event-free survival was 61.9% (95% CI = 38.1%–78.8%) from time of transplantation.
The investigators concluded: “We provide the longest follow-up in children and young adults with B-cell ALL after CD19-CAR T-cell therapy reported to date and demonstrate that sequential therapy with CD19.28ζ-CAR T cells followed by allogeneic hematopoietic stem cell transplant can mediate durable disease control in a sizable fraction of children and young adults with relapsed or refractory B-cell ALL.”
Crystal L. Mackall, MD, of Stanford University, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the NCI Intramural Research Program, Ludwig Institute for Cancer Research, Parker Institute for Cancer Immunotherapy, and others. For full disclosures of the study authors, visit ascopubs.org.
