In a new study presented at ASH 2018 in San Diego, patients with ALL who received a first stem cell transplant after CD19 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 paediatric patients, said lead study author Corinne Summers, MD, of the Seattle Children's Hospital and Fred Hutchinson Cancer Research Centre.
“We see a trend toward improved leukaemia-free survival in paediatric patients who receive their first stem cell transplant following CAR T-cell therapy,” Dr. Summers said.
In addition, either a first or a repeat stem cell transplant after CAR T-cell therapy reduced the risk of relapse in a subset of patients who were at elevated risk of having their cancer come back.
Many patients go into remission following CAR T-cell therapy, Dr. Summers said, but there are also relapses beyond one year following treatment.
The goal of the study was to evaluate whether stem cell transplantation could make remissions last.
In this phase I/II trial, researchers analysed 64 ALL patients who had received an infusion of their own T cells that had been reprogrammed to recognise and target the CD19 protein found on the surface of most leukaemia cells.
Patients had previously relapsed or had not responded to other treatment. Follow-up monitoring occurred for at least one 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, 34 had a history of previous stem cell transplant.
There were several cohorts observed:
One of the expected effects of CAR T-cell therapy is a decrease in B cells following the procedure.
This effect, known as B-cell aplasia, occurs because CAR T-cell therapy kills both normal and cancerous B cells.
Continued B-cell aplasia is regarded as an indicator that the CAR T cells are still actively preventing the patient’s cancer from coming back.
By contrast, short B-cell aplasia - that is, when B-cell counts begin to increase after CAR T-cell therapy - indicates that the CAR T-cells may no longer be working.
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 two years, said Dr. Summers.
However, among patients who did not have a stem cell transplant following CAR T-cell therapy, relapses continue to occur two or more years after treatment.
“For paediatric 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 leukaemia or lymphoma that has relapsed or been unresponsive to other therapy.
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