ASH 2018: Hematopoietic Stem Cell Transplant After CD19 CAR T-Cell Therapy in ALL
In a new study presented by Summers et al at the 2018 American Society of Hematology (ASH) Annual Meeting & Exposition (Abstract 967), patients with acute lymphoblastic leukemia (ALL) who received a first stem cell transplant after CD19 chimeric antigen receptor (CAR) T-cell therapy were less likely to experience a relapse of their cancer when compared to similar patients who didn’t undergo transplantation.
This is one of the first studies to evaluate the potential role stem cell transplantation plays in long-term outcomes after CD19 CAR T-cell therapy for pediatric patients, said lead study author Corinne Summers, MD, of Seattle Children's Hospital and Fred Hutchinson Cancer Research Center. “We see a trend toward improved leukemia-free survival in pediatric patients who receive their first stem cell transplant following CAR T-cell therapy,” Dr. Summers said in a statement.
Many patients go into remission following CAR T-cell therapy, Dr. Summers said, but there are also relapses beyond 1 year following treatment. The goal of the study was to evaluate whether stem cell transplantation could make remissions last.
Study Details
In this phase I/II trial, researchers analyzed 64 patients with ALL who had received an infusion of their own T cells that had been reprogrammed to recognize and target the CD19 protein found on the surface of most leukemia cells. Patients had previously relapsed or had not responded to other treatment. Follow-up monitoring occurred for at least 1 year.
Fourteen patients relapsed, died, or did not respond to the CAR T-cell therapy. Of the 50 patients who achieved a sustained remission after CAR T-cell therapy, 33 had a history of previous stem cell transplant.
There were several cohorts observed:
- Among the 10 patients who had their second stem cell transplant following CAR T-cell therapy, 5 remain alive and in remission after at least 24 months of follow-up.
- Of the 14 patients that underwent first HCT after CAR T-cell therapy, 2 relapsed following HCT.
- Of the 33 subjects with a history of HCT, 10 underwent a second HCT following CAR T-cell therapy, and 5 are alive and remain in remission.
- Of the 23 subjects that did not undergo a second HCT, 8 remain in remission.
- Of the three patients who did not have a stem cell transplant after CAR T-cell therapy, two relapsed and the third remains in remission after 28 months of follow-up.
In the current analysis of patients who had been followed for at least a year, those with short B-cell aplasia who had a stem cell transplant after CAR T-cell therapy were less likely to relapse, regardless of whether the transplant was their first or their second. In this group of eight patients, one died of transplant-related complications and two relapsed. By contrast, all six patients with short B-cell aplasia who did not undergo stem cell transplant after CAR T-cell therapy relapsed.
Among patients who had a stem cell transplant after CAR T-cell therapy, all relapses thus far have occurred within 2 years, said Dr. Summers. However, among patients who did not have a stem cell transplant following CAR T-cell therapy, relapses continue to occur 2 or more years after treatment.
“For pediatric patients who achieve remission after CAR T-cell therapy, undergoing a first stem cell transplant following CD19 CAR T-cell therapy appears to be beneficial,” said Dr. Summers. “For patients who achieve remission, but have a higher risk of relapse because of short B-cell aplasia, a stem cell transplant after CAR T-cell therapy appears to be beneficial whether or not they have had one previously.”
For patients with a previous stem cell transplant, the benefit of a second one after CAR T-cell therapy is unclear; it may be that among this group of patients, only those with short B-cell aplasia benefit from a second transplant, according to the authors.
Longer follow-up is needed to understand the reasons for long-term relapse after CD19 CAR T-cell therapy and whether patients with a prior stem cell transplant can benefit from receiving a second one following CAR T-cell therapy. Phase II of the trial, now underway, is testing the anti–CD19 CAR T-cell therapy in a larger group of patients with acute leukemia or lymphoma that has relapsed or been unresponsive to other therapy.
This study was supported by Stand up to Cancer, St. Baldrick’s Foundation, Alex’s Lemonade Stand, and Juno Therapeutics.
Disclosure: See the study authors’ full disclosures at ash.confex.com.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
